A11MD4: Summary- Week 1

signs of meningeal irritation

Kernig's positive due to hamstring spasm, Neck stiffness- unable to put chin on chest Brudzinskis sign- Flexing the patient's neck causes flexion of the patient's hips and knees

major area of thalamus involved in somatosensory pathway

VPL

thalamus nuclei

VPL nucleus of thalamus- indicated in dark blue

dopamine pathway structure

VTA is a major neurone that terminates within the nucleus accumbens and releases dopamine. this impacts hippocampus, straitum and frontal cortex and contributes to a constellation of emotions e.g. reward, pleasure, euphoria

causes of direct transverse myelitis**

VZV, borrelia, HTLV-1 thoracic cord

types of transverse myelitis**

Vasculitis of anterior spinal artery Direct invasion of cord

common pathologies of vessels

arterial thrombus (stroke) berry aneurysms venous sinus thrombosis

NSAIDs used to treat pain in

arthritis pain muscular pain skeletal pain toothache headache

encephalomyelitis-causing organisms that enter s.c.

arthropod -borne viruses, Ricketsii, Trypanosomes

clinical use of NSAIDs

as analgesics reduce chronic/ acute inflammation decrease temp in fever

how to identify the cingulate sulcus

first sulcus above corpus chisum

ascending myelitis causes

flaccid paralysis sensory loss

anterior horn cell myelitis causes

flaccid paralysis muscle pain no sensory or bladder dysfunction

mechanism of action of glucocorticoids

inhibit induction of enzyme

unilateral damage to frontal lobe leads to diffuclties

inhibiting saying/ doing something inappropriate

inhibition vs excitation of inhibition

inhibition involves promoting the movement of chloride ions into cell inhibiting excitation involves inhibiting sodium influx into cell

from confluence

leads to the large transverse sinus 2, one on each hemisphere runs around cerebellum drains into sigmoid sinus

corresponding genotype to UM

multiple copies of a functional allele/ allele that confers increased gene transcription

complications of drug addiction

multiple pathways

all changers in DNA arise from

mutations

genetic mutation associated with common migraine

mutations in TRESK K2P potassium channel

cerebellum

responsible for dynamic co-ordation of movement feeds back with our spinal cord co-oridation and synchronisation of mm

where does blood travel from the IJV

rest of circulation

incomplete reflex called

retching

target site for general anaesthetics

reticular activating system that is involved in arousal, sleep and wakefulness

cocaine blocks

reuptake of dopamine

contraindications when treating meningitis with steroids

risk of GI bleeding

polymorphism leads to a 20-40% increase in?

risk of a disease e.g. heart disease, Alzheimer's

which is the executive system of mode of action

route B- supervisory attention system

what happens once one mode of action has been selected

the other response is inhibited

oil-gas partition coefficient is associated with

the potency of the anaesthetic

what is retching described as

the preliminary phase to vomiting

generation of eicosanoids from AA is dependent on

the release of AA from phospholipids by enzyme phospholipase A2.

third ventricle located

around area of diencephalon

sulcus directly anterior to the marginal sulcus

central sulcus (red-coloured part)

Use of Mindfulness-Based Stress Reduction to manage pain

firbomyalgia low back pain

How is stage A of anaesthesia facilitated

i.v of inhaled anaesthetic

myelencephalon becomes

medulla oblongata

define the neurobiology of resilience

"Resilience is a class of phenomena characterized by patterns of positive adaptation in the context of significant adversity or risk" (Masten & Reed)

**EXTRA KNOWLEDGE ON SLIDE 36 OF PP**

**

CHAPTER ON PAIN IN BOOK CALLED PHARMACOLOGY BY MOORE

**

examples of causitive organisms of meningitism, that are tested for using PCR

- Meningococcal and pneumococcal on EDTA &CSF - HSV/ Enteroviruses - TB

reasons for pain being more complex that initial presentation

- Multiple somatic complaints - Negative test results - Emotional burdens - Unsatisfied with care (patient and GP)- repeatedly present as looking for explanation of cause of pain - Thick set of notes - Feeling of helplessness - Poor therapeutic relationship - Lack of collaborative working

3rd step in treating migraines

- Avoid known patient-specific migraine triggers such as stress, or dietary factors. - ß-blockers (propranolol, metoprolol), calcium channel blockers (flunarizine), anticonvulsants (valproate, topiramate; caution in pregnancy), or pre-menstrual oestrogen can be effective. The tricyclic antidepressant amitryptyline is also of value

CSF is

- CSF is a colour-less liquid that baths the brain, assists in circulating substances, it provides cushioning and absorbs shock. - CSF is produced in the choroid plexus (a group of cells that line the ventricles) and production induces CSF circulation. - The choroid plexus also acts as a medium of exchange between the extra cellular fluid and the blood stream. - contains lots of ions

Herpes Simplex Encephalitis diagnostic appearance

- Characteristic MRI appearances - EEG- temporal lobe - CSF PCR 95% sens & 94% spec vs. brain biopsy - Mortality 60% untreated in biopsy-proven cases - IV Aciclovir(high dose 10mg/kg tds) for 2-3 weeks - Reduces deaths to 19%

sensory system action

- Converts a complicated natural stimulus (energy e.g. chemical, thermal) to action potentials - APs sent to spinal cord. - Intensity and duration of the firing signals (APs) indicates how painful the stimulus is

mechanism of action of NSAIDs

- Inhibition of cyclooxygenase enzyme - Reduced generation of Eicosanoids

examples of spirochaetes

- Leptospirosis - Lyme borreliosis - Syphilis

types of HRQoL pain scales

- Medical Outcomes Study Short-form Health Survey (SF-36) - Pain Disability Index - Roland-Morris Back Pain Disability Questionnaire - Western Ontario MacMaster Osteoarthritis Index (WOMAC)

example of NO in relation to the blood gas partition coefficient

- Not great at dissolving in the blood phase - Majority of N2O remains in the gas phase - This favours the rapid entry of N2O into the brain to induce anaesthesia - Take home message - N2O promotes rapid induction and recovery from the anaesthesia

COX-2 is

- Not present all the time, inducible enzyme- generated under certain conditions - induced in activated inflammatory cells - converts AA to PGs - types of stimuli that drive the generation of the enzyme are IL-1 and TNF-alpha (cytokines)- responsible for production of prostaglandin mediators of inflammation during an insult - produces protective mechanism, in production of PGs- allows for recovery

journey of an i.v anaesthetic

- Once in the blood stream, some of the drug binds to plasma proteins and the rest remains unbound or 'free' - Drug is transported initially through venous blood and then the systemic circulation, eventually gaining access to cerebral circulation - A partial pressure gradient permits the entry of the anaesthetic to the brain where it then exerts its effect

Journey of an inhalation anaesthetic

- Once inhaled, the anaesthetic gains access into the alveoli - A partial pressure gradient (between alveoli blood and brain blood) is important in driving the anaesthetic from the respiratory pathway to the CNS - A steady state for maintenance of anaesthesia is required and this is dependent on partial pressures of alveoli, blood and brain

what is methadone

- Plasma half life > 24 hrs - Used to reduce opioid abuse- reduces physical abstinence syndrome - Psychological dependence - In presence of methadone, morphine/ diamorphine doesn't produce euphoria - Used as an analgesic clinically

halothane in terms of induction and recovery

- Readily dissolves in the blood phase and so less ideal - The system has to 'wait' until the entire blood phase gets saturated - Once the blood phase is saturated, halothane will occupy the gas phase, and then access the brain - Take home message - there is time spent waiting for halothane to saturate the blood phase before occupying the gas phase, hence, long time to induce and recover from anaesthesia

what is the phase that happens before the migraine called

prodrome attack

example of a task you may ask a patient to perform in an interpretation/ abstraction executive function test

- Similarities, 'estimates' "How are a piano and a drum alike?" 'How fast do race horses gallop frontal damage leads inability to make estimations

uses of bromocriptine

- Stopping breast milk production for medical reasons - Treating non-cancerous tumours in the brain called prolactinomas - Treating Parkinson's Disease (increases dopamine levels).

symptoms of dependence syndrome

- Strong desire or sense of compulsion to take the substance - Difficulties in controlling use (amount, onset, termination) - Physical withdrawal state (?) - Tolerance (?) - Progressive neglect of other interests, increasing time spent obtaining and taking substance - Persistence with substance despite detrimental effects: social, cognitive and physical

types of myelitis

- Transverse- acute transection of the cord - Ascending- ascending flaccid paralysis and sensory loss - Anterior horn cells e.g. polio- flaccid paralysis muscle pain no sensory or bladder dysfunction- polio, Enterovirus 71, some arboviruses and rabies virus**

how do we assess pain?

- Uni-dimensional pain assessment scales - Multi-dimensional pain assessment scales

examples of cancer pain

- Uterine cervical cancer, breast cancer - Bone metastases - Nerve compression

what is codeine

- Weak opiate (20% of morphine) - Less respiratory depression - Good anti-tussive

4 examples of processes genes influence

- the way we experience and process pain - how fast a drug is broken down in the body and how efficacious it is - how fast a drug gets into the bloodstream - the side effects of drugs

COX-1 is

- constitutive enzyme- present in all tissues, always present, actively generating eicosanoids - most tissues, blood platelets - important in tissue homeostasis

examples of NSAID GI disturbances

- dyspepsia - diarrhoea - nausea and vomiting - 1 in 5 chronic NSAID users have gastric damage - piroxicam and meloxicam highest risk

using uni-dimensional pain assessment scales

0= no pain 10= worst pain imaginable rate pain intensity by patient putting a cross on the scale, where they feel their pain lies

examples of volatile liquid anaesthetics

- halothane - enflurane - isoflurane - sevoflurane - desflurane

effects of opioids on ion channels, through the G-protein coupling

- open K+ channels - close Ca2+ channels

examples of when NSAIDs are used to reduce chronic/ acute inflammation

- rheumatoid arthritis - gout high doses needed

brainstem controls

respiratory and cardiovascular effects

examples of inducing agents

- thiopental - methohexitone/methohexital - propofol - etomidate

% of population with rare genetic disorders

1%

% of population with a polymorphic mutation

1-50%

posterior cerebral blood supply

2 vertebral aa from spinal cord and pass areas of vertebrae- large around base of pons, 2 vertebral aa merge to form 1 aa

half life of paracetamol

2-4 hrs

vol of CSF exchanged

150 ml

correlation ratio between disease and mutation

1:1

no. of thalamuses

2

ant circulation

2 carotid aa on either side of trachae feed forebrain

falx cerebri separates

2 cerebral hemispheres

falx cerebri sits between

2 hemispheres of the brain

what is diamorphine

2 molecules of morphine high lipophilicity- penetrates more rapidly than morphine broken down into morphine more potent than morphine activates reward pathway and more addictive than morphine

corresponding genotype to PM

2 non-funtional alleles

explain the 8 wk programme if MBSR

2.5h/week (+ homework) and one full day silent retreat Includes: meditation, gentle yoga and mind-body exercises Helps become more aware of habitual reactions and choose a new way to react In doing the work of this program participants realise they can break patterns of behaviour/reaction that might have held them back provides improvment in pain

mortality for listeriosis

20%

deaths from opioid pain killers

250 deaths from codeine in 2017

dura mater has how many folds

3

no. divisions of the trigeminal nn

3

no of times a day CSF is exchanges

3 thus, produce about 500ml of CSF a day

meninges are

3 layers of connective tissue that provide protection to brain

Mortality of pneumococcal meningitis

30%

features of CGRP

37 aa stored in vesicles and release

celecoxib benefits

375 fold selectivity for COX-2 over COX-1 both in vitro and ex vivo assays

the second phase lasts

4 to 72 hours

major withdrawal symptoms peak after

48-72 hrs after last dose

CTZ found

4th ventricle

% of healthy people with listeria in stool

5, due to many foods containing listeria

genetic factors that cause familial hemiplegic migraine

50% of cases with fami have a point mutation in the CACNA1A gene that encodes the pore-forming α1A subunit of the P/Q voltage-gated calcium channel (expressed on chromosome 19) Mutations result in a reduction of the flow of calcium across the membrane- functional consequence In 30% of patients with hemiplegic mirgraine, it results from mutations in ATP1A2 gene that encodes the Na+/K+ pump's α2 subunit.

what receptors are found on the nn terminals of the bipolar (opthlamic) trigeminal nn

5HT-1D heteroreceptors, which are G protein-coupled receptors

drugs used to control nausea/ vomiting

5HT3 antagonists (ondansetron, granisetron) Eicosanoid synthesis inhibition [corticosteroids] (dexamethasone) Neurokinin1 antagonist [agonist: substance P] (aprepitant, casopitant) Dopamine D2 antagonists (metoclopramide, domperidone, haloperidol) Muscarinic antagonists (scopolamine) Antihistamines (cinnarizine) Histamine H3 antagonist (betahistine: for vertigo nausea) Cannabinoid agonists (nabilone) Multiple [dopamine, 5HT & muscarinic antagonist] (olanzapine)

% of people with migraines who get a warning phase

60%

long-term complications of Meningitis

9-15% deafness (Hib ) Convulsions Visual/motor/sensory deficit

survival rate if infratentorial tumour is removed

90%

2nd step in treating migraines

triptans: 5-HT1B and 5-HT1D receptor agonists

stages of anaesthesia

A- induction of anaesthesia as patient is currently awake B- maintenance- anaesthetics at a steady state to permit surgery C- recovery

A and C-fibre action within the spinal cord

A-fibres relay touch, arrive deeper in the spinal cord than C-fibres C-fibres relay pain C-fibres release transmitters that activate neurones in the spinal cord neurones in the spinal cord signal down to projection neurones, where they converge with A-fibres a signal is then sent to the brain if projection neurone is deep down in the spinal cord, then the message runs along the spino-thalamic tract, to the brain

encephalomyelitis-causing organisms that enter via the mucosa

Herpes simplex virus, VZV

where are eicosanoids generated from

AA (arachidonic acid)

cingulate sulcus runs in a

AP direction

normal neuronal transmission, involving C-fibres

APs arrive at C-fibre terminal AP causes depolarisation and opening of calcium channels calcium enters the presynaptic terminal this causes the synaptic vesicles to fuse with the presynaptic membrane transmitters, glutamate and peptides, are released from C-fibres transmitters bind to post-synaptic receptors

different groups of primary afferent fibres

Aalpha sensory axon Abeta sensory axon Agamma sensory axon C sensory axon

physical signs of meningitis

Absence of fever Blood stream infection- ongoing sepsis and infection in CSF petechial/ purpuric rash can be found in samples of adrenals and kidneys meningeal irritation

examples of viral treatment of viral meningo-encephalitis

Aciclovir- HSV, VZV and Herpes B CMV- Ganciclovir (2nd line Foscarnet) HIV - may improve with antiretroviral treatment

physical exercise impact on depression

Active people are less likely to be depressed Exercise produces moderate clinical improvement from depression Exercise is as effective as cognitive behavioural therapy or antidepressants Exercise prevents depression relapse

an example of an everyday task using an executive function

All patients had damage to their frontal love and were showing problems with their behaviour. developed test to indentify difficulties in everyday activities. The three patients were asked by the experimenter to go to a shopping centre and purchase items, keep an appointment at a certain time and collect four pieces of information e.g. price of a pound of tomatoes or the exchange rate of the rupee. The patients were given a list of the errands (not a memory test) and instructions to follow, such as spend as little money as possible. Every single patient got into different difficulties: - One patient failed to purchase soap (on the list) as the store she visited didn't have her favourite brand. - All became embroiled in social complications. e.g one succeeded in obtaining the newspaper but failed to pay for it

treatment for listeriosis

Amoxicillin +/- Gentamicin (cephalosporins NO activity)

Management of Meningitis

Antibiotics- High dose agents that can cross blood-CSF Protect brain by ensuring adequate oxygenation Prevention of hypoglycaemia and hyponatraemia Anticonvulsants Decrease intracranial hypertension to reduce risk of herniation

action of paracetamol

Analgesic, antipyretic, weak anti-inflammatory

chronic effects of opiates

Anhedonia, constipation, depression, insomnia, dependence poor nutritional status danger of HIV and hepatitis from injecting significant tolerance

positive psychology move

Ann Masten - Ordinary magic Martin Seligman- Learned optimism Mihaly Csikszentmihalyi - Flow Carol Dweck - Fixed/Growth mindset Angela Duckworth - Grit Sonja Lyubomisky - up to 40% of our happiness is up to us Jon Kabat-Zinn- Mindfulness Based Stress Reduction

Mindfulness-based interventions & mental health

Anxiety Depression Substance abuse Eating disorders Chronic pain Improve well-benign and quality of life

describe the result of nn damage on the pain pathway

C and A-fibres damaged A-fibre damage causes allodynia, touch evoked pain C-fibre damage causes hyperalgesia no opioid receptors on A-fibres and so ineffective with A-fibre damage

bradykinin acts on

B1 and B2 receptors G-protein coupled receptors evoke action potential firing in sensory nn terminals B1 and B2 expressed by sensory nn

choroid plexus

BBB allows for exchange between ECF and blood stream

why infections in the CSF can be difficult to treat

BBB is a difficult barrier to get drugs across

actions of BK after injury

BK generated from damaged tissue and activates sensory nn terminal at its selective receptors sensory nn can release peptide substances into the local environment substances cause neurogenic inflammation release of peptides also increases vasodilation of blood vessels and thus, increase in permeability and a greater generation in BK BK can also act on sympathetic nn, in the periphery that can generate PGs pH of inflammatory exudate is lower due to high proton conc. protons can directly activate sensory nn as their nn terminals possess acid-sensing ion channels that respond to lower acidicty (greater proton no.) mast cells release 5HT which activates nn terminals release of cytokines and GFs lastly, action of PGs.

An unknown cause of bacterial meningitis in children younger than 2

Benzylpencillin and gentamicin

where do opioids effect neuronal transmission

C-fibre terminal or in brain

effect of migraine attacks on CGRP levels

CGRP levels in plasma, saliva (blood levels in cranium) are elevated

migraine-specific drugs being developed

CGRP receptor antagonists and MCA against CGRP and the CGRP receptor

2 forms of Cyclooxygenase Enzymes

COX-1 COX-2

difference between role of COX-1 and COX-2

COX-1 produces PGs in a homeostatic way COX-2 generates PGs locally, at site of injury

pathway of production of eicosanoids

COX= COX-1 and COX-2 COX enzymes converts AA to cyclic endoperoxides, which are then converted to PGs

production of CSF induces

CSF circulation

intracranial abscess picked up using

CT

imagaging modalities for pathologies of meninges

CT MRI

imaging modalities of vessel pathologies

CT MRI catheter angiography (+/- treatment)

imaging modalities for pathologies of lobes, gyri and basal ganglia

CT MRI fMRI

risks with triptans

CV disease chest pain due to coronary aa vasoconstriction

H. influenzae is treated using

Ceftriaxone chloramphenicol

S.pneumoniae

Ceftriaxone (Benzylpenicillin if sensitive) Add Vancomycin if there is a risk of the strain being antibiotic rresistant e.g. travel assoc.

group A meningococcus found in

Central Africa, subsaharan Africa

common post infection encephalitis

Chickenpox Flu A and B Measles

vaccines to prevent meningitis in young and elderly

Conjugated Hib and Meningococcal group C pneumococcal vaccines protection in <2 yr olds Men B vaccine Polyvalent pneumococcal polysaccharide vaccine (23 serotypes)

cortex role in pain

Consciousness of pain and the limbic system for emotional response

PGD2 receptor called

DP receptor

what is mindfulness meditation

Development of awareness of present-moment experience with a compassionate, non judgmental stance

short-term complications of Meningitis

Death Subdural collection/ empyema Cerebral vein thrombosis Hydrocephalus

examples of specific treatment of viral meningo-encephalitis

E.g amoxicillin for listeria Doxycycline for Q fever, Chlamydia

sigmoid sinus drains into

EJV towards heart

PGE2 receptor called

EP receptor

Mindfulness-Based stress reduction (MBSR)

Eight week course developed in the 70's by Kabat-Zinn Based on the Buddhist teachings on mindfulness but removed of all religious context- secularised mindfulness Aims to address long-term stress, which can lead to poor mental and physical health treat patients with chronic pain using mindfulness meditation

incidence of migraines

Episodic 10- 15% of people Female: Male= 3.5 : 1 Affects 16% of menstruating females 2-3 times more common if a first degree relative has it

acute effects of opiates

Euphoria, tranquility, miosis, drowsiness, itching, nausea

what is an executive function

Executive function is a description of psychological processes that underlie flexible goal directed behaviour

PGF2alpha receptor called

FP receptor

example of acute non-cancer pain

Fracture, appendicitis, MI

Go means

G other

Rapid diagnostic tests for meningitis

Gram stain for bacteria- 50% sensitivity Zn lab tests- TB few organisms present PCR Antigen agglutination tests- Cryptococcus

common primary infection encephalitis

HSV1 Enteroviruses Listeria Measles Mumps

Herpes Simplex Encephalitis causes

Haemorrhagic necrosis especially temporal lobes people present with personality changes CSF abnormal in 97% , RBCs in an atraumatic LP , mild lymphocytosis

symptoms of meningitis

Headache global Neck and back stiffness Nausea and vomiting due to raise in intracranial pressure Photophobia (don't like bright lights, non-specific)

why does moving mm affect brain function

Healthy individuals doing regular physical exercise have less anxiety symptoms Exercise improves anxiety symptoms in people with anxiety or stress-related disorders Thus, exercise is as effective reducing the symptoms of anxiety as medication

etomidate as an i.v anaesthetic

Hypnotic agent that induces anaesthesia but lacks analgesia Benefit - little to no effects on cardiovascular system Usually used for sufferers of cardiovascular dysfunction

stages of the depth of anaesthesia

I- analgesic stage II- excitement stage III- surgical anaesthesia stage IV- medullary paralysis stage

In CT and MRI, how is dye given

I.V

triptans contraindicated in

IHD

PGI2 receptor called

IP receptor

listeriosis- predisposing factors

Immuncompromised, neonates and >50 years with rising incidence with age

Pneumococcal Meningitis predisposing factors

Immunosuppression esp. if no spleen or spleen poorly functioning Alcohol Diabetes Hyposplenism Myeloma

method of action for cocaine

Increases catecholamine neurotransmitter function by preventing re-uptake

examples of neuritis

Infectious e.g. leprosy, trypanosomes, CMV, lyme neuroborreliosis (cranial), HSV+VZV (Sensory ganglia) Post infectious causes e.g. Gullian Barre syndrome- post Campylobacter jejuni , Mycoplasma pneumoniae, herpesviruses- antibodies raised by infection act on nn and can lead to difficulty self-ventilating Toxins

what is neuritis

Inflammation of a peripheral nerve

Cocaine preferred methods of administration

Inhaling cocaine better than chewing coca leaves

how does encephalomyelitis enter the CNS

Initial entry and primary site of replication: Respiratory, GIT, s.c., mucosa Then from blood into CNS Rarely via peripheral nerves

describe the aura phase

Initial visual disturbance, 30 minutes Visual area lost/ blurred surrounding area 'shimmers'

infront of lateral apertures

Interpeduncular cistern

examples of cerebral dysfunctions that can result from encephalitis

Irritability, altered personality, drowsiness Ataxia Excessively brisk tendon reflexes Signs of cerebral/ brainstem failure e.g. sluggish pupil reflexes Signs of brain swelling e.g. focal neurological signs

met-analysis on the anxiolytic effect of exercise for people with anxiety and stress-related disorders

L shows exercise is helping and R shows exercise doesn't help each square shows the mean for a study- each study shows a positive effect red diamond shows for all the studies, physical exercise has a positive effect on symptoms of anxiety and stress- significant as corner of diamond isn't touching 0; not a strong effect. study shows papers from panic disorder, generalised anxiety and PTSD; physical exercise has a positive effect

example of a task you may ask a patient to perform in a sequenced movement executive function test

LLRLLR..., 'fist, cut, slap'

what drugs enhance serotonin (5HT) function

LSD Ectasy

drugs that don't have a strong compulsion to take

LSD mescaline

main site of nociception afferent termination

Laminae I and II (most dorsal laminae)

developing growth mindsets

Learning to become more "growth mindset oriented" helps improve academic achievement

IMMPACT measurement of patient rating of improvement and satisfaction

Likert scale- similar to verbal pain scale

IMMPACT measurement of pain intensity

• NRS (0 - 10) • Rescue analgesia used

aspirin used in

MI therapy

why was the vascular theory disproved

MRI allowed us to look at blood flow changes and notice that they did not occur in patients with common migraines in patients where blood flow changes did occur, there did appear to be biphasic changes (e.g. vasoconstriction followed by vasodilation) but patterns of change didn't follow symptoms; headache started too early (first stage of migraine)

overview of key features if executive function

May be subtle deficits Normal speech, perception, IQ may be normal Loss of goal oriented behaviour and motivation Stimulus driven behaviour (utilisation behaviour) Deficit in initiation of behaviour (apathy) Impaired monitoring of responses and so problems correcting themselves when they make a mistake Disinhibition (socially inappropriate)

encephalomyelitis-causing organisms that enter via the respiratory system

Measles , mumps, VZV, Cryptococcus neoformans

Infection in listeriosis

Meningo-encephalitis brainstem with ataxia and movement disorders

triggering factors in migraine

Mental stress- 75% of cases Refractory errors in glasses Chocolate, eggs or fruit- 15% Alcohol Oral contraceptives Time zone shifts Physical exertion- 45%

uses of Lumbar puncture in meningitis

Most rapid diagnostic test Helps to distinguish between bacterial and viral causes in most cases

examples of experimental tasks to precisely assess specific executive processes- assessing working memory

N-back snaps Digit span delayed response task

examples of bacterial meningitis

N. meningitidis H. influenzae type b S.pneumoniae Unknown

where do the neurones in the meso-limbic dopamine pathway, terminate

NAC

site of drug action

NK1 antagonists treat most forms of migraine attack 5HT3 effective against migriane caused by chemo, surgery/ radiotherapy balemic patients benefit from benzodiazepine to stop the cortical centres initially reflex many drugs combined with NK1 antagonist

types of bacterial meningitis and age groups they are commonly found in

NM common in children/ young adults streptococcus penumoniae common in children younger than 2 and the elderly Listeria monocytogenes seen in neonates and the immunocompromised group B streptococci, Escherichia coli and listeria monocytogenes are found in the neonates

example of gasesous anaesthetics

NO

anaesthetics and their MAC no.

NO has least potency and halothane has the greatest potency

antagonist treatment

Naltrexone: - Therapy for opiate addiction. - Patients must be de-toxified and opiate-free for several days before naltrexone can be taken to prevent precipitating opiate abstinence syndrome. Mecamylamine: - nicotinic acetylcholine receptor antagonist. - Blocks rewarding actions of nicotine and cue-induced craving.

what is not resilience

Never experiencing a problem/pain/unhappiness Pretending as if it didn't happem something unconscious ability that cannot be changed

how does neuroplasticity work

New neurones, dendritic/axonic processes and/or changes in synaptic strength

diagnosing migraines

No definitive test or diagnosis Careful assessment of patient history Elimination of alternative causes of headache e.g. trauma, other drug treatments or rare disorders. Diagnostic criteria: must have at least 5 of the particular attacks that fullfill criteria in B-E (see sheet) phonophobia is loud noises in children, headache may be bilateral and can be associated with diarrhoea and GI disturbances

partial pressure at equilibrium when using anaesthics

PA (alveolar) ↔ Pa (arterial) ↔ Pbr (brain)

Meninges layers

PAD (inside out)

descending pathways descend to

PAG and medulla of the spinal cord

Diagnosis of viral meningo-encephalitis

PCR - replaced biopsy and viral culture but not 100% sensitivity as may not have sufficient virus in that site CSF (HSV , enteroviruses and VZV) Stool, throat swab, urine (measles, mumps) - systemic infections excreted in these sites MRI more sensitive than CT EEG

list of PGs

PGI2 PGE2 PGD2 TXA2

bradykinin increases production of

PGs reinforces positive feedback loop

eicosanoids made up of

PGs thromboxanes leukotrienes

does PG or bradykinin have a more important role in inflammation

PGs- pivotal part of inflammatory pathway

how does CYP2D6 SNPs influence patient outcomes

PM phenotype have an undetectable morphone plasma conc.- getting little analgesic from opioids UM phenotype- extensive metabolism to morphine, increased risk of adverse side effects

state the characteristics of a migraine

Painful, pulsing headache typically lasting 4 hours to 3 days, often unilateral and associated with photophobia.

ketamine as an i.v anaesthetic

Patient is unconscious but appears awake; induces amnesia - dissociative anaesthesia increases blood pressure and cardiac output Potent bronchodilator Not favoured in young adults due to induction of hallucinations

drugs that block N-Methyl-D-Aspartate (NMDA antagonists)

Phencylidine (PCP) ketamine

describe the second phase of a migraine

Photophobia- made worse by exposure to bright lights/ loud noise Nausea and Vomiting Prostrate Unable to participate in normal activities

encephalomyelitis-causing organisms that enter via the GIT

Poliovirus, other enteroviruses, Listeria monocytogenes

practical anaesthesia

Premedication atropine- decreases secretions benzodiazepine- sedation Fast induction- thiopental (intravenous) Maintain- isoflurane (inhalation) Muscle relaxation- neuromuscular blocking drug (antracurium, pancuronium, suxamethonium) Reduce pain- analgesic (opiate); also used post-operative

goals of medication in treating migraines

Primary to provide acute relief to recurrent attacks Secondary to introduce effective prophylactic treatment

how do we know about addiction?

Put catheter into different parts of brain and infuse drugs into the brain solutions go in and go through a dialysis membrane and then fluid comes back out of tube Some neurotransmitters will go across the dialysis membrane and thus, will indicate what substances have crossed

Chemoprophylaxis for meningitis

Reduce secondary cases in close contacts and households of meningococcal and Hib disease- single dose treatment to clear nasopharyngeal carriage before it enters CSF Rifampicin or ciprofloxacin clear nasopharyngeal carriage (ceftriaxone)

Encephalomyelitis variations worldwide

Seasonal variation Geographic variation Animal exposure Immunocompromised

propofol as an i.v anaesthetic

Short acting with onset of action of 30 seconds and rapid recovery decreases blood pressure and intracranial pressure Does NOT provide analgesia Accompanied by excitatory phenomena - muscle twitching, yawning, hiccups Some anti-emetic effects post recovery

thiopental as an i.v anesthetic

Similar to propofol - fast acting within 1 minute May cause apnoea, coughing, chest wall spasm, laryngospasm, bronchospasm Not commonly used now as better tolerated agents available

where does the somatosensory system receive information from

Skin, Muscle, Tendons, Ligaments and Connective Tissue

small molecules allowed through the BBB

Small molecules (oxygen, carbon dioxide, glucose, or select amino acids) are allowed to pass into the brain pathogens and larger molecules (antibodies) can not pass.

growth vs fixed mindset

Success in studies and work depend not only on cognitive ability, but also on benefits about learning and intelligence. 2 main types of people: people with growth mindset and a fixed mindset Growth mindset- intelligence develops through: - effort - (change of) strategies 0 guidance/mentoring from others Fixed mindset- intelligence is a stable characteristic

treatment of viral meningo-encephalitis

Supportive Specific treatment Viral

Causes of a Lymphocytic CSF

TB Partially treated bacterial infection Intracranial abscess can lead to inflammatory response in CSF Spirochaetes (bacteria): Viral meningo-encephalitis Lymphocytic leukaemias

TXA2 receptor caleld

TP receptor

vomiting centre has inputs from

The area postrema; detects blood chemicals (has no BBB). The vestibular system via the vestibulocochlear (8th cranial) nerve; plays a major role in motion sickness and is rich in muscarinic cholinergic and histamine H1 receptors. Vagal (10th cranial) nerve afferents activated when the pharynx is irritated, leading to the gag reflex. The nucleus tractus solitarius has high density of 5-HT3 and NK1 receptors. Vagal and other gastrointestinal afferents respond to irritation of the GI mucosa by chemotherapy, radiation, distention, or acute gastroenteritis via gut 5-HT3 receptors. Intracranial pressure receptors mediating nausea after head injury or meningitis. Descending inputs from higher centres arising from the sight or smell of vomit, situations associated with vomiting, psychiatric disorders, or with general stress.

another example of temporal aspect of planning

The patient was troubled by her inability to prepare her family's evening meal. The patient could remember the ingredients for the dishes but she could not organise her actions into a proper sequence. She might assemble all of the ingredients but become flustered and switch her preparation from one dish to other, or mix up which items belonged together. incoherent behaviour

why is genotype-related opioid prescribing important

There has been a marked rise in prescribing of opioid drugs in the UK and the trend to increased prescribing continues. Data for 2013 show that 21.7 million prescriptions were issued (not including opioid substitution treatment for addiction) with a total cost of £289.8 million. The increase in prescribing has been predominantly for the treatment of non-cancer pain: i.e. chronic pain The increase in prescribing has been associated with increased costs to the NHS.

causes of arbovirus infections

Togaviridae, Flaviviridae and Bunyaviridae

stimuli detected by somatosensory system

Touch Brush Pressure Tickle Temperature (hot, cold, warm) Pain

meningitis symptoms that can occur in what other infections?

UTI, dysentery SAH, malignancy, NSAIDs

which molecules cross through the BBB the quickest

Unbound molecules lipid soluble molecules unionised molecules

examples of supportive treatment of viral meningo-encephalitis

Ventilatory support Blood glucose and electrolytes monitored and corrected (hypothalamic involvement) Anti-epileptics Control cerebral oedema Cooling if extreme hyperthemia

VPL is

Ventral posterolateral nucleus

Neuro psychological tests of Executive Function

Wisconsin Card Sorting Task Tower of Hanoi/ London Stroop Rey Figure Test Temporal Memory BADS (The Behavioural Assessment of the Dysexecutive Syndrome) All come with 'Norms'

example of tasks you may ask the patient to complete in a verbal fluency executive function test

Words beginning with F, A, S in 60 seconds- someone with dementia may only provide about 17 Members of categories (towns, animals)

2 considerations in relation to the blood-gas partition coefficient

a gas phase and a blood phase thus, how much of the inhalation anaesthetic will dissolve in the gas phase and how much will dissolve in the blood phase.

the OPRM1 A118G SNP leads to

a loss of mu-opioid receptor function

brain development similar to

a mm increase in no. of synapses related to environmental enrichment

what did researchers find in people who felt no pain

a mutated SCN9A gene this resulted in a defective protein channel called NaV1.7 this resulted in no pain

opioid extract contains

a no. of alkaloids inc morphine

what is congenital insensitivity to pain

a rare inherited condition where the person cannot feel physical pain and has no sense of smell

what happens in rare genetic disoders

a single mutation can have a big effect mutation can cause disease

NaV1.7 is?

a sodium voltage-gated channel expressed only in sensory and nociceptive neurones

neuropeptides of opthalmic division of trigeminal nn

a variety of neuropeptides one is the calcitonin gene related neuropeptide (CGRP) another in substance P

what are both Group B streptococci and Escherichia coli a part of

a woman's normal vaginal flora

if present with meningitis, % presenting with pneumonia

around 50%

define pleocytosis

abnormally large number of lymphocytes in the CSF.

superior/ dorsal

above

drug processing in the body

absorbed distributed metabolised eliminated - all these processes occur using molecules

WHO committees recommend what terms, in relation to substance addiction

abuse and dependence

divisions of selecting task relevant information

accentuate attended information excluding irrelevant information

IMMPACT measurement of patient disposition

according to CONSORT recommendations- how patients flow through trial e.g. no. of patients who completed the trial

ranking of harm rating

according to classification systems that purport to relate to the harms and risks of each drug However, the methodology and processes underlying classification systems are generally neither specified nor transparent, which reduces confidence in their accuracy and undermines health education messages. A group developed and explored the feasibility of the use of a nine-category matrix of harm, with an expert delphic procedure, to assess the harms of a range of illicit drugs in an evidence-based fashion Ectasy is not, numerically, a problem

what is hydrocephalus

accumulation of cerebrospinal fluid (CSF)

describe the result of high intensity pain on the pain pathway

activates C-fibres this has a protective role opioid receptors are on C-fibres and can inhibit them

what happens when morphine binds to the presynaptic µ-opioid receptor

activates Gi singalling pathway inhibits adenylyl cyclase reduces cAMP inhibitory affect on protein kinases and signalling in cell- suppressant effect on cell closes calcium and opens potassium channels hyperpolarises presynaptic terminal and so it is harder for transmitter to be released reduces transmitter release and so less excitability and less transmission of signal

describe the result of tissue damage on pain pathway? treatment?

activation of C-fibres all the time hyperalgesia opioids used as an analgesic

third migraine theory

activation of sensory nn in trigeminal ( CN III) nn nn can release neurotransmitters can cause vasoliation V1's activity is enhanced during attacks

what does NICE recommend in treatment-resistant cases

acupuncture or gabepentin

categories for duration of pain

acute chronic

NSAIDs are a type of acute or chronic analgesic? why?

acute as side effects are damaging in long-term use

causes of encephalitis

acute immune-mediated encephalitis unknown arbovirus and rabis are common causes in some part of the world

Uni-dimensional pain assessment scales useful for

acute pain

why isn't the duration of symptoms (acute vs chronic) a good discriminator of pain

acute pains can go on for a long time pain may be more complex than initial presentation

classification of pain

acute vs chronic cancer vs non-cancer pain mechanisms

when do extradural haemorrhages occur

after a skull fracture (80% of the time) in young patients rapidly expands due to bleeding bone and aa running along the outside of ten dura, that have severed

when do withdrawal symptoms subside

after a week

when are Uni-dimensional pain assessment scales used

after surgery

drug classes of opiates

agonists of G protein-coupled opioid receptors (µ receptors mainly)

examples of local anaesthetics

all end in -caine lignocaine bupivacaine ropivacaine cocaine

what do 5HT-1B receptors do

also G protein-coupled receptors on blood vessels this contributed to vasoconstriction

mechanisms of action of local anaesthetics

alter voltage gated sodium channels uncharged form of anaesthetics gains access into intracellular fluid becomes charged once inside the intracellular fluid charged anaesthetic associated with and closes the sodium gated channel and so sodium ions can't enter the cell thus, removing the excitatory mechanism that processes pain

effects of drugs on dopamine levels

amphetamine shows an increase in level of dopamine, no influence on metabolism of dopamine cocaine has a slower onset of an increased level of dopamine nicotine shows an increased metabolism level of dopamine due to increased metabolite level nicotine also shows a greater increase in dopamine level in the accumbens than in the caudate ethanol shows dose dependent- dopamine level; increasing ethanol increases dopamine level

descending pathways start in

amygdala and hypothalamus

what is lymphocytic CSF

an abnormal increase in the amount of lymphocytes in the CSF

familial hemiplegic migraines are accompanied with

an aura

BBB is

an interface that ensures the circulatory system (blood) is kept separate from the extracellular fluid/CSF. Pericytes and astrocytes also play a role in maintaining the BBB

properties of high conc. of cocaine

anaesthetic properties

COX-2 inhibitors actions

analgesic/ anti-inflammatory effects in arthritis, low back pain

endogenous substance that works of cannabinoid receptors

anandamide anandamide increases release of dopamine

aa teritories

anterior covers less of brain middlde has largest teritory lenticulostriate aa feeds basal ganglia lenticulostriate aa come of middle circulatory aa sup cerebellar covers the vast majority of the cerebellum

describe the man-on-fire syndrome

any activity e.g. putting on a sweater feels like hot lava is being pour onto their bodies

maximise exercise-induced brain gain

any exercise better than no exercise aim for aerobic exercise e.g. running, swimming, cycling should be part of daily routine e.g. walking should be 30-45 mins, 3-5 times a week exercise at the beginning of the day- more focused

best NK1 antagonist

aprepitant substance P is major output neurotransmitter from vomiting centre

Which meningeal layer has blood vessels and cerebral spinal fluid?

arachnoid matter

Lymphocytic CSF called

aseptic meningtis

uncover task-orientated perfusion

ask them to perform a task whilst undergoing scan e.g. MRI

an example of an experimental task to precisely assess specific executive processes- assessing temporal/ recency memory

ask which item on the card the patient hasn't seen in the pack/ has seen most recently in the pack

examples of short-term analgesic NSAIDs

aspirin- COX-2 inhibitors paracetamol ibuprofen

functional neuroimaging

assesses for functions e.g. metabolism, task-orientated perfusion etc

structural neuroimaging

assesses for normal anatomy and thus, seeks to ind anything which may be distoring it e.g. tumour, haemorrage

corresponding genotype to EM

at least 1 functional allele

corresponding genotype to IM

at least 1 reduced fucntional allele

name the first phase of a migraine

aura

classical migraine described as having an

aura, even if no prodrome and then stage 2

where are primary afferent fibres found

axon bundles

what structure important in choice making

basal ganglia

telencephalon bcomes

basal ganglia cortex

what surrounds the endothelial cells

basement membrane

BBB image

basement membrane in yellow colour

most commonly used assessment tool in speciality pain assessment

brief pain inventory

inferior/ ventral

below

accessing CSF

between L3- L5 spinal cord now fibres- cauda equina

fourth ventricle located

between pons and cerebellum

where is the subarachnoid space

between the arachnoid membrane and the pia mater

hyperalgesia

bigger pain response for a given painful stimulus

colour of CSF on a CT

black

aneurysm, spotted in image B, caused? treated with?

bleeding to subarachnoid spaces treated with endovascular coiling

bradykinin comes from

blood and tissue

complications of haemorrhage in brain

blood compresses brain due to limits of skull

how does venous blood from the vv reach the IJV

blood drains from vv into the dural venous sinuses and then into the IJV

venous drainage

blood flow can be bidirectional veins can flow into each other major vein, middle of brain- superior sagital sinus

inferior anterior cerebellar

blood supply of ant aspect of cerebellum comes after merge of 2 vertebral aa

inferior posterior cerebellar

blood supply to posterior aspect of cerebellum

Subarrachnoid space contains

blood vessels and CSF fluid

pathogenesis of bacterial meningitis

blood-borne spread- common as organisms usually travel from nasopharynx to the blood stream across the choroid plexus pneumococcus present in the nasopharynx esp. in very young/old- risk of passing into CSF and causes meningitis cerebral capillary epithelium becomes leaky and so plasma proteins enter and pressure rises photophobia

2 things to consider within anaesthetics

blood-gas partition coefficient oil-gas partition coefficient

i.v anaesthetic drug given as

bolus dose

periosteal layer of dura mater adheres to

bone

what is NICE recommended for adults with frequent chronic migraines

botulinum toxin type A

different regions of spinal cord project to different regions in

brain

diencephalon sits on top of

brainstem

midbrain part of

brainstem

describe the vascular theory

build up of metabolites e.g. changes in PCO2, PGs, H+- humoural disturbance in blood vessels causes an abnormal cerebral BF. first, vasoconstriction inside meninges (intra-cerebral vasoconstriction)- causing aura second, vasodilation of extra-cerebral blood vessels- causing headache vessels released associated pain.

name of bumps and fissures in brain

bumps- gyri fissures- sulci

reasons for acute pains going on for a long period of time

burns dressings changes sickle cell disease and so have regular crisis- infrequent occurrence but throughout the whole of their life flare ups of RA

how can the secondary theory (changes in neurones) be mimicked in animals

by application of potassium to the animals

nocicpetion activates

c-fibres pain pathways

issues with antagonist effects

can be overcome by increasing dose of drug

use of the discovery of the defective NaV1.7 channel

can be used to develop drugs that target the NaV1.7 use these drugs as an alternative in adults who suffer from chronic pain and cannot be treated using current analgesics e.g. NSAIDs or to avoid the side effects of drugs such as opioids

other actions of naloxone

can reverse action of opioids given in cases of opioid overdoses

tectum- Posterior view of brain and dorsal view of midbrain

can see the superior and inferior collliculi

purpose of communicating aa

can take over if issues with main aa e.g. in hyperplasia of the R anterior cerebral aa, the aa can be supplied by the L ACA, via the communicating aa

why is microscopy for TB not done

can't always be seen few organisms per mil and so a negative result doesn't mean no infection

categories for cause of pain

cancer non-cancer

difference between cancer and non-cancer pain

cancer pain: - progressive - may be mixture of acute and chronic - due to surgery - compression of nerves - location of tumour non-cancer pain: - many different causes - acute or chronic

why can't Group B streptococci and Escherichia coli be gotten rid of from the mother

cannot be killed by antibiotics

cerebellum located

caudally

action of triptans

cause constriction of cranial blood vessels and subsequent inhibition of neuropeptide (CGRP) release.

issues with cause of chronic non-cancer pain

cause may not be obvious

An unknown cause of bacterial meningitis in children older than 2/ adults is treated using

ceftriazone amoxicillin added if patient immunocompromised or older than 50

N. meningitidis is treated using

ceftriazone or benzylpenicilin if sensitive

choroid plexus is

cells that line ventricles

response to Lymphocytic CSF

cellular response in CSF

cisterna magna sits directly below the

cerebellum

signs of encephalitis

cerebral irritation/ dysfunction

considerations when changing route of opioids

change in metabolism effects of a single injected dose are 6x that of a single oral dose

brainstem role in pain response

changes in BP, increases respiration increases orientation towards stimulus

long-term neuroplasticity due to

changes in gene expression relies on epigenetic changes- changes in moelcules around DNA

I.V contrast of subarachnoid haemorrahge is done to?

check for no bleeding aneurysm can see out-pouching of vessels

5HT3 best against

chemo vomiting 70-90% of patients protected against

important area in vomiting centre called

chemoreceptor trigger zone (CTZ)

in the past, what age group had haemophilus influenzae type b been common in

children under 5

CSF produced in

choroid plexus

use of longer-acting analgesic NSAIDs? used in conjunction with?

chronic conditions in conjuction with opioids for post-operative pain chronic pain e.g. cancer pain as it has both an inflammatory and nn driven basis

examples of chronic non-cancer pain

chronic low back/ spinal pain arthritis

opioid use in chronic pain

chronic pain states have reduced effectiveness of opioids, in terms of analgesia

CSF drains into

cisterna magna biggest cistern

about IMMPACT

clarified different domains that should be included within trials in relation to drugs domains: - Pain intensity - Physical functioning - Emotional functioning - Patient rating of improvement and satisfaction with treatment - Other symptoms and adverse effects of drugs during treatment - Patient disposition and characteristics e.g. if patients withdrew due to side effects, lack of effectiveness etc; allows to see how wide-scale effective a particular treatment is

% of suffers with classical and common migraines

classical- 15% common- 85%

tretment of nausea

combination of anti-emetics and mild sedation (benzodiazepine) can be used to reduce severe nausea. Corticosteroids are not very effective for control of acute vomiting 5HT3 antagonists are not very effective against non-chemotherapy vomiting.

effectiveness of combination therapies and some examples of their uses

combination therapies show additive benefits in highty emetic chemotherapy-induced emesis, a combination of a NK1 antagonist, a 5HT antagonist and a corticosteroid give 85-80% protection against vomiting

posterior aa

comes off the top of the basilar aa runs towards the temporal lobe supplies the inferior surface of temporal love, hippocampus and medial aspect of occipital lobe

brain reward pathways

compulsion to take/do the addicted substance learn to use the addicted substance as it is pleasurable, rewarding e.g rats will self-administer some drugs and these drugs activate reward pathways

why are steroids not used to treat pneumococcal infections

concerns that resistant strain antibiotic may be penetrated**

superior sagittal sinus moves post to form

confluence of sinuses

cerebral aqueduct

connects the third and fourth ventricles

brainstem

conscious and unconscious function most functions

fluoroscopy

constant stream of X-rays gives dynamic/ functional information

opioid side effects

constipation nausea anti-tussive effects drowsiness dizziness low BP physical addiction bronchospasms hives respiratory depression

what are the 2 modes of how action selection is normally achieved

contention scheduling- perceive environment and select which best suits you; stimulus drive supervisory attention system- cognitive demanding decision making, requires weighing up 2 choices where one option is the norm

what is important when using Uni-dimensional pain assessment scales

continuity and similarity of use ensures pain is comparative between 2 different healthcare professionals

medulla oblongata becomes

continuous with the spinal cord

pia mater follows

contours of brain

what happens if you injure yourself

convergence of signals from different fibres- a single sensory neurone in the CNS can receive input from many sensory receptors amplifies signal entering spinal cord amplifies pain reception- indicates damage

how does vomiting work

coordinated involuntary reflex involving powerful sustained contraction of the abdominal, chest wall and diaphragm muscles (which greatly increase intra-gastric pressure) opening of the cardioesophageal sphincter, glottis and jaws. rapid evacuation of stomach contents up to and out of mouth- stop breathing and epiglottis closes over trachea so we don't inhale any vomit

nuclei communicate with

cortex

thalamus gateway to

cortex

mutations in TRESK K2P potassium channels may cause

cortical spreading depression and lead to familial migraines

neonate radiology

cranial ultrasound

withdrawal effects of opiates

cravings insomnia restlessness diarrhoea mm and bone pain vomiting cold flushes with goose bumps kicking movements

importance of sulci

define boundaries of lobes within brain

bradykinin generated

de novo- during inflammation locally, at site of inflammation

use of 5HT-1D agonists in treating migraines

decrease CGRP release, basis of triptans

how are NSAIDs analgesic

decrease sensitisaton and activation of nn terminals

resolution to second phase

deep sleep loss of headache

what is a lamina

describe different layers down spinal cord lamina I and II in the uppermost part of grey matter, dorsal horn of spinal matter deeper lamina and deeper into spine (more frontal)

3 most important layers of meninges

dura mater- tough arachnoid mater pia mater- soft matter, very thin

examples of morphine-like analgesics

diamorphine codeine methadone

examples of benzodiazepines

diazepam; lorazepam; midazolam

below ventricles

diencephalon

forebrain forms

diencephalon telencephalon

issue with Cyt P450

differ between ethnicities

difference between C and A fibres input in the spinal cord

different level of entry to spinal cord

difference between sensory and mm axons

different names same essential role

difference between meningococcal disease around the world

different serum groups can be due to genetics

issue with serum group B meningococcal

difficulty producing vaccine against

example of a direct effect toxin that causes neuritis

diptheria

different effects of toxin-causing neuritis

direct effect indirect effect

median aperture located

directly inferior to the 4th ventricle

neuropathic and Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scale pain scales used to

distinguish between neuropathic pain from other types of pain

central sulcus marks

division between the frontal and parietal lobe

absence of bacteria in gram stain

doesn't mean no infection

characteristics of a subdural haemorrhage

doesn't tough gyri most common in elderly, who have slightly shrunken brains bridging veins crossing the meninges can be severed by minor trauma and lead to a venous bleed can be acute or chronic

receptors in CTZ

dopamine D2, 5-HT3, opioid and acetylcholine), a neurokinin (substance P) is the major output transmitter.

bromocriptine drug class

dopamine agonist

many drugs of abuse increase what substance release

dopamine in the NAC

alchol admin for a better 'rush'

drink more and in a shorter space of time

dopamine pathay

drug dependence and reward pathways

greater rush/ euphoria if

drug is injected high is greater- faster and higher peaks in brain dopamine level

why can't extradural haemorrhage cross the midline? what is the result?

due to the suture haemorrhage continues to expand and put pressure on the brain beneath it

Which meningeal layer protects the brain

dura mater

meningeal layer has lifted parts called

dural reflections

spaces within dural layers are called

dural venous sinuses

Meningococcal disease in England and Wales

during WWI and WWII found in uni students

when is Uni-dimensional pain assessment scales carried out

during movement- not necessarily walking at rest e.g. asking someone to cough

use of migraine diaries

ease of diagnosis help to avoid further attacks by identifying triggers nausea? aura? location? throbbing? female- relation to menstrual cycle? eating anything in diet that is associated with migraine attacks?

why is cerebellum useful in terms of orientation of the brain

easily identifiable orientate self

importance of lateral sulcus

easy to identify

forms of addiction

eating sex exercise shopping football falling in love- parallels with substance misuse, pleasure

what other group does not present typically with meningitis

elderly and immunocompromised

exercising too much

elevates cortisol levels and so feel stressed can be symptomatic of mental health diseases e.g. eating disorders

what does nausea proceed

emesis

amygdala and hypothalamus roles

emotional processing stress

myelitis can happen with or without

encephalitis

case definition of encephalitis

encephalopathy

example of an endogenous opioid

endorphines e.g. NA

blood vessels of BBB are composed of

endothelial cells, which fit together tightly. When two cells touch, their membranes join together to create a barrier that allows passage only of selected material between the blood and brain. These joined edges are called tight junctions.

characteristics of a subarachnoid haemorrhage

enters gyri

stress-induced analgesia pathway allows for

escaping dangerous situations to somewhere safe e.g. on a battle field, a fox, danger etc activates descending inhibitory control pathway- shuts down excitation in spinal cord, shuts down pain signals in the short-term survival mechanism

what does genetic variation of the mu-opioid receptor depend on

ethnicity can be found in 2-48% of populations

effects of opioids

euphoria analgesia sleep

effects of cocaine

euphoria and excitement, increased capacity for work

what happens if PGs injected into someone

evokes a painful response PGs able to activate pain pathways

physical exercise and memory

exercise improves memory People more fit have better memory and larger hippocampus Exercise increases BF to the hippocampus and improves memory- shown in fMRI R shows exercise improves memory diamond shows exercise improves memory but not significantly

importance in difference between nociception and pain

experiments determine nociception but not pain

venticles

extend far anteriorly and posteriorly cirulates substances around brain as CSF flows through ventricles contains CSF

what type of haemorrhage has a lens-shaped haemorrhage

extra-dural haemorrhage

Assessment of Pain in Children

faces scale associate with which pain they are feeling

true or false: Health care personnel know best the nature of the patient's pain

false

true or false: Psychogenic pain is not real

false

true or false: The amount of damage determines pain intensity

false

folds of dura mater

falx cerebri Tentorium cerebelli Falx cerebelli

AA metabolised by

fatty acid cyclo-oxygenase enzyme

superior cerebellum aa

feeds most of cerebellum

pain describes

feeling/upset/sadness felt includes psycholgical component

Fentanyl vs. Morphine potency

fentanyl is more potent, per mg, than morphine AND heroin

Define antipyretic

fever reducing

VPL role

final relay before signals reach the cortex integration noxious and tactile stimuli

meningitis in infants

flaccid- later opisthotonus bulging fontanelle due to increased ICP fever and vomiting often the only sign strange cry convulsions

what is the inflammatory soup

fluid that alters function of the substance surrounding the nn

pia mater

follows contours of brain small delicate protective (green line)

thus, what is favoured in an inhalation anaesthetic

for a lot of the anaesthetic to be in the gas phase so that it can reach the brain and induce anaesthesia

physical exercise impact on depression- systematic review on cochrane library

found 35 studies that were conducted with patients with depression they measured the patients depression level R of graph shows exercise makes depression worse but : shows exercise was beneficial in depression most studies lie on the L overall (diamond), positive impact of exercise on depression again, diamond not touching line and so shows significant benefit of exercise on depression

CSF fluid runs

from lateral ventricles into intervetnricular froamen then into third ventricle flows into cerebral aqueduct (opening in midbrain) then into fourth ventricle - CSF flows from superior to inferior direction

lobes of brain

frontal temporal occipital parielal

central sulcus separates

frontal and parietal lobes

WCST indicates what sort of brain damage? why?

frontal lobe due to memory deficit

dura mater

function of holding brain in place has folds in it

exmape of a drug used to treat chronic neuropathic pain

gabapentin

types of inhaled general anaesthetics

gas volatile liquids

which phase is favoured for the anaesthetic to reach the brain?

gas phase

why isn't gentomycin used to treat adults with an unknown cause of bacterial meningitis

gentomycin doesn't enter CSF in adults

anterior aa

go straight up between 2 hemispheres and then head in a posterior direction supply ant aspect of frontal lobes and white matter

benefits of spinal opioids

good for chronic pains

issues with genetic polymorphisms that affect drug metabolism

great variation in response of individuals to standard doses of drug therapy can lead to treatment failure or life-threatening adverse drug reactions in some patients

sulcus means

groove

substantia nigra is

group of dopamine producing cells die in parkinson's disease

neurobiology of exercise

growth factors cause connections and dendrites to develop in then brain exercise causes an increase in BDNF, FGF-2, VEGF and IGF-1 in the hippocampus BDNF and FGF-2 are made within the hippocampus due to changes in DNA methylation and histone modification, within the gene in the hippocampus, as a result of exercise VEGF and IGF-1 come from mm, through the circulatory system and then into brain- boost neurogenesis and synaptogenesis

nicotine replacement therapy

gums, patches, sprays ineffective in long-term smoking cessation- 1 yr quit rates not greatly affected

what is an extradural haemorrhage

haemorrhage is outside all the dura layers inc. the periosteal layer

what is a subarachnoid haemorrhage

haemorrhage within the subarachnoid space can be caused by trauma

action of PCP and Ket

hallucinogenic

impact of oil-gas partition coefficient on potency

halothane easily dissolves in lipids compared to N2O as has a low oil-gas partition coefficient thus, a high oil-gas partition coefficient permits an easier entry, of the anaesthetic, through the BBB.

Oil-gas partition coefficient and MAC values

halothane has a high oil-gas partition coefficient and a low MAC value N2O has a low oil-gas partition coefficient but a high MAC value halothane easily dissolves in lipids cimpared to N2O thus, a high oil-hgas partition coefficne,t that permits the etnru of the aneaesthtic through he BBB.

neuropathic pain and opioids

hard to treat neuropathic pain with opioids

feature of neurones of the spinal cord

have a peripheral receptive field recording from one neurone, from one part of spinal cord, can stimulate a particular part of the body

clinical effect of the OPRM1 A118G SNP

having at least 1 G allele means that the patient needs more opioid after surgery patients also had less pain relief

unilateral damage to the frontal lobe

head injury degenrative disease stroke surgery

most common presenting complains

headache head trauma seizure focal neurological deficit

diamorphine also called

heroin

changes in CSF due to bacterial infectious meningitis

high WBC count predominant cell type if neutrophiles are the predominant cell type CSF: serum glucose <0.5

a lower MAC no. associated with

high potent anaesthetics

red nucleus

highly vascularised important as location of extraperamital tract

brainstem is part of the

hindbrain

PGE2, PGI2 and PGD2 synergise with

histamine release from mast cells bradykinin release from blood cells

what is working memory

holding information of what you have just done

tentorium cerebelli

holds cerebellum in place

ventricles

holes that reach far in AP direction filled with CSF

common pathologies of ventricular system

hydrocephalus

relating inputs to the vomiting centre, to treatment

identify cause and find most appropriate drug e.g. if dealing with motion sickness, and thus, activation of the vestibular centre then use antihistamines (H1/ M1 antagonists) if dealing with infection gastroenteritis/ chemotherapy/ surgery of GIT that has activated the vagus, then 5HT3 receptor antagonists will be more effective in some cases, useful to initiate vomiting reflex

warning for use of bromocriptine

if you have a tendency to do particular things, need to be monitored whilst using bromocriptine bromocriptine will increase your compulsion to do certain activites e.g. sex, gambling, excessive eating/ spending

what is meant by tolerance of drugs? what causes this?

if you take an opioid repeatedly over time, its ability to produce analgesia reduced need a higher dose to get the same effect G-protein coupled receptors are prone to desensitisation and so need to activate a greater no. of receptors to get analgesia

role of imaging in stroke

image using CT if stroke is being cuased by haemorrhage, don't give an anti-clotting agent if stroke is caused by clot, treat with thrombolysis

Where does a subdural heamorrhage occur?

in between the dura and arachnoid layer, outside fo the hemisphere

C fibres arrive?

in the superficial dorsal horn of the spinal cord, where pain input arrives

pain signal pathway- way to remember

in through door-dorsal horn out through vent- ventral horn

dopamine release following sex

increased dopamine release

warnings about COX-2 inhibitors

increased risk of heart attack, stroke and cardiovascular death.

if a substance removes GABA from being released

increases dopamine release

effects of amphetamines

increases wakefulness and conc. decreased fatigue and appetite thus, performance enhancing increases euphoria, libido, energy, self-esteem, self-confidence, aggression increased BP and cardiovascular tone, tachycardia

types of i.v. general anaesthetics

inducing agents benzodiazepines dissociative anaesthesia

treatment of bacterial meningitis dependent on

infecting agent and risk factors for patient if patient is young or immunocompromised, treatment should be altered accordingly

why is PCR done for some infections

infections are harder to grow using microscopy techniques

transverse myelitis

infective and non-infective causes

CSF flowing in an

inferior direction but needs to go up and around brain (arrows on diagram)

what is encephalitis

inflammation of the brain

What is meningitis?

inflammation of the meninges

what is myelitis

inflammation of the spinal cord

functions of the dopamine pathways

influences motor function drives compusion and perserveration

result of increased blood flow

influx of inflammatory substances from the blood

tentorial tumours

infratentorial- common in cause of tumours in children, 50% supratentorial- common in adults, form of metastasis

categories of inhaled anaesthetics

inhaled i.v

other name for man-on-fire syndrome

inherited erythromelalgia (burning sensation)

hippocampus

initially curves posteriorly curls forward- lateral to medial curve function of memory spacial navigation

what does IMMPACT stand for

initiative on methods, measurements and pain assessment in clinical trials

largest aa in angriogram

internal carotid aa

which cistern is directly in front of the midbrain

interpeduncular cistern

pathologies associated with head trauma

intracranial haemorrhage

common pathologies of meninges

intracranial haemorrhages infections/ inflammatory diseases

Cyt P450 action

involved in drug metabolism and bioactivation- transform drugs into soluble molecules to be excreted

common pathologies of lobes, gyri and basal ganglia

ischmaemia (stroke) parenchumal haemorrhage tumour/ inflammation/ infection neurodengerative diseases

hence, why is acute pain useful

it acts as a protective mechanism

histamine causes

itch

common migraine is

just stage 2- unilateral throbbing headache

treatment stratergies

justice for drug offenders, crime, social security, NHS every pound spent on treatment saves a pound on health service and criminal justice costs

example of a dissociative anaesthesia

ketamine patient is unconscious but appears to be awake

define ataxia

lack of voluntary coordination of muscle movements

CT lateral view of skull

lamboid suture separates occipital and parietal squamosal suture separates frontal and parietal sinus

marginal sulcus used for

landmark for central sulcus (red-coloured part)

describe Aalpha and Abeta sensory axons (group I and group II mm axons)

large diameter myelinated fast condution velocity relay messages about proprioception and mechanosensitivity (non-painful e.g. touch, pressure)

subcortical blood supply

large part of cerebral hemispheres is white matter caudate is a c-shaped structure lenticulostriate aa- small stroke in basal ganglia can have dramatic consequences

corpus callosum

large white matter structure sits on top of ventricle

describe the receptor reserve for opioids

large- great no. of receptors on terminal only need to activate a proportion no. of receptors to get analgesia (if low tolerance)

stronger stimuli evoke

larger receptive potentials and thus, a greater number and higher frequency of action potentials frequency of firing encodes the painful stimulus

CSF exits through

lateral apertures CSF accumulates in places with space, called cistern

CSF circulation- flow

lateral ventricle > interventricular foramen > third ventricle > cerebral aqueduct > forth ventricle > cisterna magna > interpeduncular cistern > cisterna pontis

list of ventricles

lateral ventricles interventricular foramen fourth ventricle third ventricle cerebral aqueduct fourth ventricle

caudate nucleus located

laterally to ventricles moves in a lateral to medial direction

basal ganglia of brain-

layers inside putamen called pallidi external capsule is outside the putamen

effect of migraine attacks on platelet 5HT levels

levels depleted during migraine attacks urinary levels increase

issue when treating bacterial meningitis

limited treatment options

paracetamol metabolised in

liver

questions about pain?

location intensity description of pain- aching, burning, stabbing, shooting

supra and infra refer to

locations within tentorium

LC

locus ceruleus

what is fibromyalgia

long-term condition that causes pain all over the body. characterised by mm pain with stiffness and localised tenderness

describe the N-back task

looking for a repeating 2 letters and must make a response when you see the same thing then there is 2 back, where a response must be give when there are 2 letters the same with an alternate in the middle

internal carotid aa becomes

loops and goes sideways to become anterior and middle cerebral aa anterior cerebral aa run into the midlinmidline and anteirorly

why is codeine a poor analgesic

lots of genetic variance, some fatalities unpredictable anaesthetics

changes in CSF due to tuberculous infectious meningitis

low WBC count mononucleocytes are the predominant cell type CSF: serum glucose <0.3 high protein- 0.5 < X 3.0

why infection can be established in the CSF

low protein immune system not ready to clear organism as no complement, no innate immunity low IgG no lymphatics

normal CSF

low protein, between 0.2-0.4 g/L CSF glucose is lower than blood glucose, ratio of 0.5- need to do a blood glucose to compare ratio <5 white cells

a higher MAC no. associated with

lower potent anaesthetics

define prostrate

lying stretched out on the ground with one's face downwards.

changes in CSF due to cryptococcal infectious meningitis

lymphocytes respond to fungal infection and so high mononucleocyte count high protein- 0.5 < X 3.0 CSF: serum glucose <0.5 low WBC count

basilar aa

major cerebral aa feeds a lot of the brainstem rare to have a stroke

roles of PGI2 and PGE2

major role- hyperalgesia vasodilator- increase blood flow decrease platetel aggregation

white dots on brain function

make connections with CSF drains CSF into venous drainage system

what sits in between the cerebral peduncles

mammillary body

sphenoid sinus

maxillary sinus under orbit

nociceptors

mechanical (e.g. pinch) thermal (>37 degrees) chemical- inflammation

if thrombolysis unsuccessful at treating a clot-causing-stroke, treat with

mechanical thrombectomy

closest part of brain to spinal cord

medulla oblongata

temporal lobe function

memory contains hypocampus location/ navigation another language centre

deep layer of dura mater called

meningeal layer

purpuric rash associated with

meningitis disease

if signs of meningism co-exist with encephalitis, diagnosis

meningo-encephalitis

rash normally caused by

meningococcus

midbrain forms

mesencephalon

type of dopamine pathway

meso-limbic dopamine pathway

describe the descending inhibitory control of pain

message going into PAG, NRM input from LC collectively, desceding inhibitory control pathway is excitatory from PAG to NRM. pathway from NRM to spinal cord is INHIBITORY makes it harder for pain message to be sent to brain

MBSR for pain management in cases of fibromyalgia

meta-analysis significant improvement in short-term QoL of patients but no significant improvement in long-term

DOPAC and HVA are

metabolites

hindbrai divides into

metencephalon myelencephalon

agonist substitution for opiates

methadone treatment for opiate abuse- has a long half-life and doesn't activate receptors as strongly as opiates prevents opiate withdrawal and so blocks effects of illicit opiate use and decreases opiate craving if people are stable on methadone, can function in society reduces exposure to HIV by stopping injecting very low rate of complete cessation of heroin use in methadone patients hard to wean off methadone

cerebral aqueduct can be recognised as

mickey mouse's mouth

ambient cistern is located directly posterior to

midbrain

thalamus in continuation with

midbrain

3 areas of brain stem

midbrain pons medulla

age where prevalence of migraines peaks

middle age

aa that commonly ruptures in extradural haemorrhages

middle meningeal aa

what has been suggested, in the past, as potential causes of migraines?

migraine due to vascular disturbance - vascular theory due to a change in neurones- cortical spreading depression theory sensory nerve activation theory

effects of cannabis

mild euphoria effect in moderate doses dysphoric in high doses very low acute toxicity but some concerns about precipitation of psychosis in chronic heavy users. stimulates appetite through actions on feeding centres in the hypothalamus and possibly gut. analgesic

mindfulness on gray matter density

mindfulness increases gray matter density- cell bodies of neurones MRI scan before and after meditating

examples of mindfulness-based interventions

mindfulness-based stress reduction (MBSR) love and kindness meditation progressive mm relaxation breathing meditation

activities that can affect behaviour, by mediating changes in the brain

mindset physical exercise yoga-mindfulness sleep

How is stage C of anaesthesia facilitated

monitoring to assure recovery

changes in CSF due to viral infectious meningitis

mononucleocytes are the predominant cell type protein- 0.4< X < 0.8 CSF: serum glucose >0.5 WBC count- 50-1000 cells/mm^3/106 cells/L

functions of serotonin pathways

mood memory processing sleep congnition

difference in drug use between students and convicts

more heroin use in convicts than students

pros of using numerical rating scale over verbal

more variance in pain and thus, more able to measure change in pain

examples of opiates

morphine, heroin, methadone, codeine

hindbrain

most acenstral and conserved part of brain

what's in the ventral horn

motor neurones

necessary inhaled dose of anaesthetic to prevent

movement to a standard surgical stimulus (skin incision) in 50% of patients

clinical relevance of CYP2D6 UM

much greater risk of opioid related-adverse events due to increased production of morphine benefits for not taking opioid metabolised by CYP2D6 serious adverse reactions inc respiratory depression, circulatory depression, shock, cardiac arest and death

sinuses scan

mucus circulates around sinuses and oral pharynx- clears pathogens blockage of mucus circulation can cause sinusitis

pharmacogenetics side effects with NSAIDs

mutations in cyt P2C9 can decrease the metabolic activity of this enzyme and increase the risk of NSAIDs side effects e.g poor metabolisation of celecoxib leads to elevated blood levels and the potential for adverse effects due to drug accumulation

cause of man-on-fire syndrome

mutations in the SCN9A gene thus, defective NaV1.7 channel, which is hypersensitive to stimuli

polymorphism refers to

mutations that exist in the population

antagonist to opioid receptors

naloxone

what is the stroop task

naming colours despite the colour of the text

examples of longer-acting analgesic NSAIDs

naproxen, piroxicam

lentiform nucleus

narrower medially than laterally

taxi driver experiment

need a huge memory a scan of the hippocampuses showed than the taxi drivers had different hippocampuses taxi drivers had less anterior hippocampus but had a larger posterior hippocampus correlation between no. yrs working as a taxi driver- greater no. months spent driving, the more different they are from their controls

Assessment of pain in dementia/ patients unable to communicate

need to assess pain by observation done by assessing: - Facial expression - Verbalisations - Body movements - Changes in interpersonal interactions - Changes inactivity patterns or routines - Mental status changes - Change in BP, respiratory rate etc.

recovery from second phase

needed due to being exhausted and unable to participate in regular exercise and activities

Different brain activation in expert meditators vs novices during focused meditation

neural correlates of attentional expertise in long-term meditation practitioners red areas are more active looking at brain activation when resting and meditating C has more active areas in those who are master meditators areas in blue are more active in novies

nociception describes

neural process of pain what happens when you put your hand over a flame

hypothalamus role in pain

neuroendocrine and stress responses to insult

what happens if CSF flow is impaired

not as much of an issue in children, skull expands builds up and enlarges ventricles causes neurological impairments treatment- surgery to drain CSF using a shunt and drain into adbomen

issues with spinal opioids

not compatible with daily life

rash in differential diagnosis

not diagnostic

basis of neuroplasticity- quote

neurones firing together wire together

low back/ spinal pain is a mixture of which types of pain? result of this?

neuropathic and nociceptive different treatments may be needed

side effects of chemotherapeutic agents

neuropathic pain

what are the changes in the brain a result of

neuroplasticity

amphetamines taken up by? affect?

nn ending releases dopamine and other amines on the nn ending

describe the features of the opthalmic division, of the trigeminal nn

nn has cell bodies, thus, cranial nucleus has bipolar neurone- has nn endings that project in both directions part of the sensory nervous system- takes afferent information to the CNS and releases neurotransmitters at both ends inferior end occurs in the dorsal horn of spinal cord and synapses with sensory input superior end, nn terminals are on meninges and blood vessels

neuropathic pain is due to

nn injury induced pain resulting from surgery, DM, chemotherapy

do patients always experience all phases

no

recruitment increases

no. of responsive receptors and their fibres increases their strength of their signal, into the CNS

categories for pain mechanism

nociceptive inflammatory neuropathic (dys)functional

neurones that specialise in pain called

nociceptive neurones

summary

nociceptors detect painful stimuli, high threshold C fibres are slower than Adelta fibres send message to dorsal horn of spinal cord messages in spinal cord cross to controlateral side and reach brainstem, cortex (conscious sensation) and limbic system

PGs enhance

nociceptors response to bradykinin (BK) increase sensitivity of nociceptors

signals to thalamus (blue line)

non-painful and painful stimuli

what are you looking for in the microbiology

normal CSF count or signs of inflammation or infection

describe the two neurone network

normally in the brain, there are excitatory and inhibitory pathways- a balance between them regulates the excitatory pathway. GABA inhibits the glutamateric pathway. Thus, if GABA neurones are activated, they release GABA onto the excitatory neurone, causing it to fire less. If the GABA neurone is not activated, glutamate is released from the glutamatergic and excitation occurs.

contraindications with lumbar puncture when diagnosing meningitis

not done until a CT head is done can lead to hernia due to difference in intracranial pressure risk of bleeding due to abnormal clotting

clinical relevance of CYP2D6 PM

not getting enough analgesia same frequency of side effects as normal metabolisers (1-8% of people)

development of tolerance to cocaine

not same level of tolerance as tolerance to opiates cocaine increases dopamine level if animal has previously been given cocain over a period of time, tolerance increases and so same dose doesn't give the same increase in dopamine levels. Thus, not the same level of euphoria

NAC

nucleus accumbens

NRM

nucleus reticularis paragigantoncellaris

spinal effect of opioids

opioid receptors are concentrated in the superficial horn of spinal cord- localised to the place where fibres that relay pain are terminated hence, can inhibit pain without inhibiting touch 70% of opioid receptors are on the presynaptic terminals (30% on postsynaptic terminals) C-fibre terminals is a powerful site of morphine action

difference between nociception and pain

pain is psychological nociception is activation of a pain pathway

why complex definition of pain

pain and injury (pathology) not always linked under stressful conditions, people and animals can suffer quite serious injuries without feeling the pain immediately- endogenous opioids. some people experience pain in the absence of a lesion

examples of synthetic opioids

pethidine fentanyl

how does morphine cause an excitation of descending inhibitory control pathway

opioid receptors in the brain are often on GABA neurones When morphine is released, it inhibits the GABA neurone as morphine is an inhibitory ligand This prevents the inhibition of the excitatory neurone so it fires more, causing more excitation. Hence, opioids cause a greater excitation (disinhibition) of the pathway. This is because of a greater opioid binding in the PAG that drives the PAG- NRM pathway and a greater opioid binding in the NRM that drives the NRM- spinal cord pathway The NRM-spinal cord pathway is inhibitory and so there is more inhibition. Opioid receptors in the spinal cord are inhibitory as well.

result of sudden withdrawal by heavily-dependent users in poor health

occasionally fatal heroin withdrawal is considered to be less dangerous than alcohol/ barbiturate withdrawal

specific treatment for

ommon, non-viral infectious causes of viral meningo-encephalitis

define contralateral

on the opposite side of the body

where does the parieto-occipital sulcus run

on the outside of the brain, all the way towards the midline

epidural space in spinal cord

on top of dura

epidural bleed

on top of dura skill is broken better prognosis as blood not pressing on brain, blood has somewhere to go

what do Uni-dimensional pain assessment scales do

only assess pain intensity

mechanism of pain

open sodium ion channels allow sodium to flow into cell and continue the processing of pain

where are opioid receptors found in the CNS and what is the affect?

opioid receptors present in PMG and NRM when morphine is given/ when endogenous opioids are released, ligands bind to receptors in PMG and NRM this actives more strongly the pathway from PAG to NRM and thus, actives the inhibitory response, in the spinal cord, more strongly thus, morphine activates the descending inhibitory control pathway and decreases excitation in the spinal cord

NSAIDs used in combination with? why?

opioids decrease post-operative pain

divisions of trigeminal nn

opthalamic (eye)- V1 maxillary (cheek)- V2 mandibular (lower face and jaw)- V3

opthalaic aa heads towards

optical structures

standard oral morphine used

oral morphine

fentanyl

orally active highly potent short duration used in anaesthetics and drug overdoses

pethidine

orally active less potent short duration used in labout

bioavilability, absorption and metabolism of aspirin

orally bio available rapid absorption, 75% metabolism in liver

frontal skull X-ray

orbit less dense than bone around as has less bone if fluid in sinus (dense and white) can indicate fracture of one of the sinus walls if someone has had a fracture of the orbit walls, air can leak into orbit and so hovers in an eyebrow line

example of condition that causes tissue damage

osteoarthritis

examples of when morphine is used as an analgesic drug

osteoarthritis to treat chronic pain

extra-axial haemorrhage means

outside brain

high doses of cocaine leads to

overactivity of sympathetic system (uptake blockade) hypertension tachycardia hyperpyrexia dilated pupil palpitations

describe the phase I metabolism of codeine

oxidised into morphine by CYP2D6, in the liver

physical exercise and attention

p value of 0.03 physical exercise had better attention and processing speed in brain can help with people with dementia

bradykinin causes

pain

allodynia

pain response to non-painful stimuli hard to treat L side of normal threshold common feature of chronic pain

categories of neuropathic pain

pain that affects the peripheral nerves- most common type of neuropathic pain pain that affects the spinal chord pain that affects the brain

Adelta and C sensory axons activated by? message relayed to?

painful stimuli message about painful stimuli relayed to spinal cord

another example of extreme pain disorders

paroxysmal extreme pain disorder

red pathway role

pathway in emotional aspects/ suffering of pain

people at risk of Spirochaetes

people who work with sewage people who canoe

cerebral aqueduct surrounded by

periaqueductal gray

PAG

periaqueductal grey matter

superficial layer of dura mater

periosteal layer

COX enzymes mainly found in

peripheral tissue

Teaching activity: Three people who have been genotyped for the opioid receptor OPRM1 A118G polymorphism and for the CYP2D6 alleles These people are about to undergo a surgical procedure and you are thinking of prescribing codeine to cope with post-operative pain. How effective will codeine be for each of the patients? Which patient has the highest risk of side effects? Would you recommend other type of analgesics (such as NSAIDs) rather than codeine to any of these patients? person A: AA genotype in opioid receptor and EM in CYP2D6 receptor. person B: GG genotype in opioid receptor and PM in CYP2D6 receptor. person C: AG genotype in opioid receptor and UM in CYP2D6 receptor.

person A: good pain relief from codeine as AA is normal variant and average risk of adverse side effects as normal processing of codeine - ok to use codeine person B: poor pain relief and average risk of adverse side effects. - safe to use codeine but not affective person C: suboptimal level of pain relief but high risk of adverse side effects - unsafe to use codeine

functions of frontal lobe

personality thinking attention motivation motor control

arachnoid granulations

pertrusions outside the arachnoid mater directly enters into superior sagital sinus, passing back into the venous circulation

describe drug metabolism

phase I- drug is oxidised by Cyt P450 so that the drug becomes more polarised and a chemically active compound phase II- conjugation- more water-soluble, less active and be excreted in urine

where is AA derived from

phospholipid bilayer of cells

physical exercise on adult neurogenesis

physical exercise increases adult neurogenesis neurogenesis happens in the red U red are basic stem cells and proliferate stem cells some cells leave proliferation stage and become neuroblasts (green) and then fully grown neurones this process takes around 28 days exercise increases no. proliferating cells in the brain Ki67 is maker that stains cells that are proliferating, not dividing- this increases with exercise cells need to differentiate into fully functioning neurones- exercise helps with fully differentiating neurones some cells die before they become neurones

layer tightly wrapped around the gyri

pia mater

subcomponents of executive function inc

planning behaviour inhibitory control attentional flexibility working memory monitoring

initial feeling associated as the prequel to addiction

pleasure

difference between treatment of pneumococcus and meningococcus

pneumococcus needed to be treated for longer than meningococcus

causes of anterior horn cell myelitis

polio enterovirus 71 some arboviruses rabies virus

metencephalon becomes

pons cerebellum

CSF can accunlate between

pons and medulla in cisterna pontis

4 possible phenotypes of CYP2D6

poor metaboliser- PM intermediate metaboliser- IM extensive metaboliser- EM ultra-rapid metaboliser- UM

absence of fever indicates

poor prognosis

what is opium extracted from

poppy juice

proprioceptors detect

position of Body

cerebral blood supply

post and ant circulatory system

parieto-occipital sulcus runs

posterior end of brain runs in a superior-inferior direction

example of peripheral type of neuropathic pain

postherpetic neuralgia neuropathic pain following shingles Diabetes mellitus

what happens when morphine binds to the postsynaptic µ-opioid receptor

potassium leaves cell any transmitter bound that manages to be released and binds to its postsynaptic receptor, finds it harder to depolarise membrane pathway harder to activate any transmitter that gets through is blocked

function of PGE2, PGI2 and PGD2

powerful vasodilators

where are µ opioid receptors present

pre and postsynaptic terminals

Haemophilus type b (Hib)- history

pre-treatment- caused meningitis in children flare up of cases lead to a booster vaccine being introduced, creates for long-term immunity

what is important when talking about abuse of a substance

predisposing factors in the individual genetics environment

N-back assesses

prefrontal function

define antitussive

prevent or relieve cough

causes of vasculitis transverse myelitis**

primary infection e.g. VZV, TB, syphilis, schistosmiasis post infection- MMR, upper respiratory infections

precentral gyri

primary motor cortex

characteristics of emesis

protective reflex (to expel ingested toxins) shown in man and most meal-feeding mammals (rats can't vomit), and is associated with nausea

inferior posterior cerebrellar aa

provides blood supply to very posterior aspect of the cerebellum

arachnoid space in spinal cord

purple space

example of stimulus driven behaviour

putting on a pair of glasses you find on the table

pros of Uni-dimensional pain assessment scales

quick easy to use fairly reliable

issues with crack

rapid dependence

what do the PGs do when there is an inflammtory response

rapid generation of PGE2 and PGI2 by local tissue cells and blood vessles vasodilation presence of mast cells that release PGD2 and histamine chronic inflammation recruits monocytes and macrophages macrophages release PGE2 and TXA2 multiple cells generate PGs at site of injury

Spirochaetes carried by

rats

issues with tolerance

repeated dosing of opioid lose receptor capacity of receptor population less analgesic affect and so need to take more and more opioids

what is the RAT system

recognise assess treat

why is there not always a pathophysiological consequence to tolerance of opioids

recycling can occur

neural changes underlying successful second language word learning using fMRI

red shows how different those who successfully learnt vs those who were unsuccessful some areas of the brain are more active in relating to tone discrimination

PGE2, PGI2 and PGD2 collectively cause

redness and increase blood flow potentiate the generation of histamine and bradykinin on blood vessels and peripheral nn positive feedback loop

Meningitis and steroids

reduce long morbidity in Hib meningitis (dexamethasone) Give prior to antibiotics for beneficial effect concern if resistant strain antibiotic penetration may be affected

if a substance increase GABA release

reduction in dopamine release

motor neurones important for

reflex pathway

what do 5HT-1D heteroreceptors do

regulate the release of the other neurotransmitter, CGRP, reducing CGRP release

examples of genetic variation in the mu-opioid receptor

rs1799971 (G) allele in the OPRM1 gene causes the normal amino acid at residue 40, asparagine (Asn), to be replaced by aspartic acid (Asp) this SNP is also called A118G, N40D or Asn40Asp

inferior sagittal sinus

runs along the cygulate gyrus

posterior cerebral aa

runs towards temporal lobe feeds inf surface of teporal lobe hippoycampus medial aspect of occipital lobe

how do neonates acquire Group B streptococci and Escherichia coli

rupture in membranes of mother's birth canal**

bleed in subdural space

rupture of connecting veins of the sagittal sinus blood fills up space between dura (pink) and subarachnoid (arachnoid mater)

layers of the brain's support and protection

scalp periosteum bone dura mater archnoid mater pia mater

diseases that cause radiation of pain

sciatica

what do signals from nociceptor afferents activate

second order neurones in spinal cord

why are new neurones important

sedentery- fewer neurones exercise increases no. neurones thought transmission is more effective if brain is densely packed with neurones

examples of a experimental tasks to precisely assess specific executive processes- assessing attentional control

selecting task relevant information

ability to detect different types of sensations

selectivity of receptors that detect stimuli

sensory system is made up of

sensory receptors at the end of nn (found in skin) receptors, when activated, send AP to spinal cord spinal cord has neurones that are activated.

dorsal normally associated with

sensory system

parietal lobe functions

sensory system intergrating sensory info language centre

flax cerebelli

separates cerebellar hemispheres

what is 5HT

serotonin

3rd stage migraine treatments used in

sever attack and or those going on for more than 2 months

brief pain inventory

several questions asking pain intensity 7 questions that looks at how pain has interfered with other aspects of life/ function e.g. mood, normal activities, relationships, sleep, normal work, enjoyment of life

hypothalamus

sex function regulate circadian rhythm thirst hunger endocrine system

issues with Triptans

short-acting poor CNS penetration*

MBSR for pain management in cases of low back pain

short-term significant benefit on pain long-term, no significant improvement on pain

middle aa

shunting device prevents inhibition of blood flow 90% of strokes occur in this aa ascends through lateral sulcus and has largest teritory supplies lateral temporal, parietal and frontal lobe

what do opioid receptors have in common

similar function esp. µ and δ made up of 7 transmembrane spanning regions coupled to Go/Gi proteins Inhibit adenylate cyclase and reduce CAMP alter ion channels

most common polymorphisms

single nucleotide polymorphisms (SNIPs)

intensity of stimulus encoded by

size of responding receptor population and the no. of fibres activates

C fibres come from

skin

feature of peripheral receptive fields

small able to discriminate where the sensation is coming from

thalamus

small sits directly above midbrain important for sensory system- perception of pain

THC mimics effects of

small endogenous lipid messengers e.g. anandamide

describe Adelta sensory axons

smaller diameter finely myelinated reasonable conduction velocity signal painful and non-noxious stimuli high mechanical and high thermal threshold stimuli

crack administration

smoked

tobacco preferred methods of admin

smoking cigarettes better than chewing tobacco

use of opioids

socially medically for 1000 yrs

causes of epidural bleed

some form of trauma

cons of Uni-dimensional pain assessment scales

some patients struggle with quantifying their pain thus, use other types of scales to assess pain intensity

reflections create

spaces within the dura meningeal layer

thalamus plays role in

spacial discriminatory aspects

blue pathway role

spacial discriminatory aspects of pain

what happens in retching

sphincter doesn't open and nothing is ejected

importance of difference between C and A fibres

spinal cord able to tell if input is painful or not

meninges surround

spinal cord and brain

examples of spinal type of neuropathic pain

spinal injury MS arachnoiditis syrinx tumour

TRESK K2P (potassium channel) is found in

spinal neurones and dorsal root ganglia, involved in pain pathways

what are withdrawal reflexes

spinally-mediated nociceptive events that result in the withdrawal from the stimulus

describe the cortical spreading depression thoery

spread of depolarisation in neurones starting from visual cortex and spreading forward, as a wave of depolarisation- cortical spreading depression this activates neurones and triggers the migraine attack

descending inhibitory control of pain

starts in cortex and sends message to PAG signal from PAG to NRM (part of medulla) NRM projects to spinal cord and activates an inhibitory pathway, using inhibitory transmitters inhibitory transmitters suppress pain signalling in the spinal pathway - starts as an excitation and ends as an inhibitory consequence in spinal cord - activated during stress-induced analgesia - LC releases NA in spinal cord and also inhibits signalling - bidirectional pathway.

first drugs specifically designed for migraines?

still in clinical trial CGRP receptor antagonists Monoclonal antibodies

hyerpalgesia

stimuli that normally evoke a small pain response, evoke a large pain response R side of normal threshold common feature of chronic pain

normal response to painful stimulus

stimulus response function receptive threshold after which you experience pain, in a linear relationship, until it plateaued off.

3 sinsus thatfeed into confluence

straight sinus superior sagittal sinus occiptal sinus

rash can also be caused by

streptococcus, Hib sepsis and enteroviral infection

pathologies assocaited with focal neurological deficit

stroke

examples of brain type of neuropathic pain

stroke MS tumour epilepsy syrinx

degree of dependence liability of Benzodiasepines

strong difficult to wean off

types of neuroimagine

structural functional

HRQoL used in

studies of epidemiological impact of pain

all of aa and vv that supply the brain are found in

subarachnoid space

between 2 layers of the arachnoid mater is the

subarachnoid space

unilateral damage to frontal lobe leads to what type of damage

subcortical and cortical

spaces in brain

subdural epidural subarachnoid

what type of haemorrhage has a cresenteric-shaped haemorrhage? why?

subdural haemorrhage follows convexity of the cerebral hemisphere as not limited by sutures

examples of peptide substances released when bradykinin acts on the sensory nn

substance P

peptide from vomiting centre

substance P

central and precentral sulci also run in a

superior-inferior direction

inferior anterior cerebellar aa

supplies most anterior aspect of the cerebellum

superior cerebrellar aa

supplies vast majority of cerebellum

affect of opioids

suppressants

CT of skull

sutures don't join until second yr of life

induction of vomiting

swallow pill to cause vomiting

alternatives to opioids

switch route of admin e.g. change to s.c. or epidural spinal opioid- epidural/ intrathecal

what happens when tissue is damage

synthesis of eicosanoids is driven, thus, production of PGs PGs found at site of tissue damage

analogues of substances with a similar effect to morphine

synthetic endogenous

midbrain can be located using

tails can be located using mammillary bodies

interventional neuroradiology

take a catheter and put into cerebral vessels pass smaller tubes within the aneurysm and drop titanium and platinum coils- these exclude aneurysm from circulation repeat of a cerebral angiogram should show the aneurysm to be excluded from circulation

amphetamine action

taken up into nn endings increases release of dopamine

1st step in treating migraines

taking NSAIDs e.g. paracetamol, diclofenac take early in attack don't help with aura

mesencephalon divides into

tectum (sup and inf colliculi) tegmentum cerebral peduncles

lateral sulcus marks division between

temporal and frontal (and some parietal)

other identifiable feature of the brain

temporal lobe (where arrow is pointing)

issues with congenital insensitivity to pain

tend to die in childhood due to injuries or illness going unnoticed children with this illness often sustain damage in and around the oval cavity e.g. bitting off the tip of their tongue. they can also suffer from fractures to bones, have unnoticed infection or suffer burn injuries

example of an indirect effect toxin that causes neuritis

tetanus/ botulism

diencephalon becomes

thalamus hypothalamus

third ventricle near

thalamus and hypothalamus location

cisterna pontis sits between

the PONS and the medulla oblongata

what is neuroplasticity

the ability of the brain to change in response to the envirnoment

what does the Wisconsin Card Sorting Test (WCST) measure

the ability to learn concepts and considered a good measure of frontal lobe functioning rule is as you take a card from the pack you place it under the card with the same no. of items. someone says wrong and patient then has to sort cards according to a different type of class e.g. put card under other cards with the same colour

what is temporal/ recency memory assessing for

the ability to remember the order of events/ actions

cocaine comes from

the alkaloid that is extracted from the coca tree

what is the cortical spreading depression theory now thought to be the cause of

the aura but not the migraine attack itself backed up by an MRI experiment

what does the interpeduncular cistern sits between

the cerebral peduncles

definition of potency of drug

the higher the potency of the drug, the less of the drug required to give benefits the minimum alveolar conc. (MAC)

hence, what is 5HT invovled in

the migraine attack

opioids agonists inhibit

the release of excitatory transmitters from the afferent nn fibres that relay the pain message inhibit neurones release in GIT, lungs and gut

Executive function is required when

the situation requires a response that competes with a strong, habitual response- something you routinely do but have to do something else a novel solution is required or the task is not well learnt the situation requires error correction or troubleshooting

blood-gas partition coefficient is associated with

the speed of induction and recovery to the anaesthetics- speed of anaesthesia

calcarine sulcus is the location of

the visual cortex

what does the elevated CGRP levels, during a migraine, indicate

this neuronal pathway is activated during migraine attacks and so releases its neuronal peptide content

role of TXA2 (thromboxane)

thrombotic vasoconstrictor

each thalamus conntected by

tiny white matter structure, ventricles

when need to access CSF

to eliminate diagnosis of meningitis

uses of benzodiazepines

to reduce anxiety

Superior anastomotic vein of Trolard

top arrow

mechanoreceptors detect

touch pressure vibration

posterior/ caudal

towards the back

caudal part of brain

towards the back of brain

anterior/ rostral

towards the front

name of the stalks that connect the 2 layers of arachnoid mater

trabeculae

other drugs affected by CYP2D6 genetic variation

tramadol guidelines for prescribing based on someone's genotype

What is NaV1.7 responsible for? how?

transmitting the pain signal in pain-specialised neurones It does so by mediating the inward sodium current of excitable cells, which is responsible for generating and propagating APs in neurones

uses of Benzodiasepines

treating anxiety

true or false: Giving analgesics regularly will sometimes start drug dependence

true

true or false: Patients with major illnesses have more pain

true

pathologies associated with seizures

tumour, congenital abnormality

pathologies associated with headache

tumour, inflammation, infection

treatment dependent on

type of pain

Bleed in subarachnoid space

type of stroke called subarachnoid haemorrage

vomiting centre found

under cerebellum midline

second phase of migraine

unilateral throbbing headache

features of C fibres

unmyelinated conduct slowly, slow conduction velocity small diameter act be activated by a range of painful stimuli polymodal- respond to mechanical, thermal (hot and cold), chemical (inflammatory)

foods with high listeria contents

unpasteurised cheese

characteristics of nausea

unpleasant sensation that immediately proceeds vomiting. A cold sweat, pallor, salivation, self absorption, loss of gastric tone, duodenal contractions, and reflux of intestinal contents into the stomach often accompany nausea.

what is Chemoprophylaxis

use of drugs to prevent disease

angiograms visulaise aa

used if suspect stroke sagittal angiogram- 1st coronal angiogram- 2nd

uses of inducing vomiting

useful if patient has taken an overdose of tablets or if patient has taken too much alcohol can't use in patients who may have a respiratory impact

How is stage B of anaesthesia facilitated

using inhaled anaesthetics as the rate and level of distribution, within the patient, is easier to monitor

treatment for group A meningococcus

vaccine

treatment for pneumococcal meningitis

vaccine

why is haemophilus influenzae type b now uncommon

vaccine found

partial receptor agonists in smoking and opioid cessation

varenicline and buprenorphine increases levels of dopamine and decrease demand on receptor

vomiting centre activated by

variety of stimuli Iatrogenic (e.g. chemotherapy, radiotherapy, opiates, antibiotics) Drugs e.g. alcohol Motion sickness and Meniere's disease Pregnancy Poisoning (e.g. ethanol) Gastroenteritis and stimulation of the pharynx Meningitis and intracranial haemorrhage (raised pressure) Bulimia nervosa- psychosocial reflex

CGRP causes

vasodilation and local inflammation of the meninges causing the migraine

role of PGD2

vasodilator decrease platelet aggregation

arbovirus infections transmitted by

vectors: mosquitoes ticks sandflies

spaces within the dura meningeal layer contain? called?

veins dural venous sinuses (venous spaces)

people on contraceptive pill more likely to develop

venous sinus thrombosis

anatomical terms in reference in brainstem

ventral is closer to tummies dorsal becomes closer to backs

where are the cell bodies in the meso-limbic dopamine apthway

ventral tegmental area (VTA)

simple executive function tests

verbal fluency sequenced movements interpretation/ abstraction

issues with CYP2D6

very variable

causes of Encephalomyelitis

viral and non-viral primary infection/ post infecitous direct invasion, vasculitis (interupts blood supply) or immune response to infection

occipital lobe function

visual

what is emesis

vomiting

reflex of vomiting coordinated by

vomiting centre

thermoreceptors detect

warm cool hot

degree of dependence liability of cannabis? why has this change?

weak stronger strains e.g. skunk with greater THC are causing a greater degree of dependency

CTZ characteristics

weak BBB can detect chemical many receptors on neurones

PGs produce their biological effects through actions at

well defined receptors

when does the 4th stage of the depth of anaesthesia occur

when things go wrong

non-painful inputs arrive?

where blue dot is, lower down in dorsal horn of spinal cord

cerebral hemsiphere

white matter cortex

Proposed mechanisms of action of general anaesthetics

will either block 5HT3 receptor, neuronal nicotinic receptors or glutamate receptors the blocking of these receptors will dampens down the system and promotes anaesthesia also want to activate inhibition which can be achieved by activating the GABA A receptor/ glycine and promotes inhibition by inhibiting sodium into cell and thus, excitation

how does encephalopathy present

with an altered level of consciousness, cognition, behaviour or personality persisting for more than 24 hours and 2 of more of: - Fever/ history of fever (≥38°C) - Seizures and/or focal neurological findings - CSF pleocytosis (>4 WBC/µL) - EEG findings compatible with encephalitis - Abnormal results of neuroimaging (with evidence of brain parenchyma involvement)

pain signals are set up with

withdrawal reflexes

action of THC

works on Gi protein-coupled receptor cannabinoid receptors inhibits neurotransmitter release in brain

what happens during the prodrome attack

yawning mood or appetite change

facial X-ray, angle looks up chin

yellow is mandible if someone has had a blow to the head, the 'elephant trunk' is disrupted

arachnoid mater

yellow substance, membrane

Do NSAIDs reduce pain and inflammation?

yes

morphine receptor

µ opioid receptor

receptors that opioids act at

µ-, δ-, κ-receptors

Describe neuropathic pain

• Caused by a lesion or disease of the sensory nervous system • Tissue injury may not be obvious • Does not have a protective function • Descriptors - Burning, shooting, pins and needles, numbness • Less localised

give the definition of pain

• "An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage" • "Pain is a subjective experience that can be perceived directly only by the sufferer. It is a multidimensional phenomena which can be described by pain location, intensity, temporal aspects, quality, impact and meaning. Pain does not occur in isolation but in a specific human being in psycho-social, economic and cultural contexts that influence the meaning, experience and verbal and non-verbal expression of pain."

Describe nociceptive pain

• 'Good' type of pain • Sensation associated with the detection of potentially tissue-damaging noxious stimuli e.g. touching hot object • Body's natural, reflexive response • High threshold type of pain • Stimulation of nocicpetor • Protective

historical techniques of anaesthetics

• 'knock-out' blows to the head • carotid artery compression • ingestion of ethanol and herbal mixtures

features of general anaesthetics

• Alters central neural processing • Readily reversible loss of consciousness with a decreased response to painful stimuli and muscle tone • Divided into inhalation and intravenous anaesthetics

list of the effect of morphine, acting via a µ-opioid receptor

• Analgesia • Euphoria / dysphoria • Tolerance (major issue) • Dependence • Constipation (40 % on oral opioids)- doesn't show same tolerance profile as analgesia • Anti-tussive

Properties of NSAIDs

• Anti-inflammatory • Analgesic • Antipyretic

McGill pain questionaire

• Assesses pain quality and characteristics • Assess pain using categories of words that the patient tickets off: - Sensory - Affective - Evaluative e.g. how the individual interprets their experience of pain

what do patients want from an analgesic

• At least 50% pain reduction • No worse than mild pain • Relief from related problems - Sleep disturbance, improved mood • No side effects • Those who get better do well - Improvements in fatigue, mood, and sleep, general measures of function, QoL and ability to work - All of this is near impossible and so must set realistic expectations from patients

IMMPACT measurement of physical functioning

• BPI pain interference scores

IMMPACT measurement of emotional functioning

• Beck Depression Inventory • Profile of Mood States - only one needs to be done

features of local anaesthetics

• Block generation and conduction of nerve impulses at local contact site • Consciousness is maintained

routes of infection of meningitis

• Blood-borne- invade blood and then direct invasion into CSF- common • Can spread from infections in different areas • Spread if CSF in other areas e.g. ear • Parameningeal suppuration e.g.otitis media, sinusitis • Direct spread through if defect in the dura e.g. post surgery, trauma • Direct spread through the cribriform plate (rare)

types of multi-dimensional pain assessment tools

• Brief Pain Inventory • McGill Pain Questionnaire • Neuropathic Pain Scale • Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scale • HRQoL

transmission of tactile messages

• Central branches of touch afferent fibres ascend in the dorsal columns • Synapse in the dorsal column nuclei • Cross the midline in the medulla • Ascend through the brainstem, contralaterally, to the medial lemnisus and then onto the thalamaus • In the thalamus, synapse with cells in various ventral posterior regions (ventral posterior medial and ventral posterior lateral nuclei) • From the thalamus, projections are sent to the primary somatosensory cortex (S-I), postcentral gyrus of parietal lobe- tight mapping of surface of body onto the cortex to discriminate regions.

clinical uses of opioids

• Choice of opioid • Tolerance - higher plasma concentration to achieve same pharmacological effect • Opioid is influenced by pain sensitivity • Route of administration govern the speed of onset and duration of effect

burden of long-term pain

• Depression • Sleep disturbances • Fatigue • Impaired physical functioning • Impaired concentration • Time off work • Possibly lose job • Less active

why do we assess pain

• Determine severity and impact of pain • Evaluating treatment outcome • Stratifying and personalising treatments • Screening for undiagnosed pain

what is involved in recognising pain

• Does the patient have pain? • Do other people know the patient has pain e.g. nursing staff, physio

facts (ish) about pain

• Everyday pain is an almost universal experience • Some people have genetic abnormalities which means that they are unable to experience pain • Usually pain warns us that we have injured ourselves in some way • Pain, particularly acute pain, usually gets better with time and may not need to be treated • Pain is an ambiguous perception • All pain is affected by how we are feeling at the time • and what about pleasurable pain e.g. gym- pain not an indication of damage but a sign of an activity enjoyed

describe cancer pain

• Features of acute and chronic pain • Can affect all organs of the body - May be acute on chronic • Often mixed inflammatory and neuropathic pain (due to compression of nn) • Usually worsens over time if untreated

side effects of paracetamol

• Few side-effects with therapeutic doses • Regular intake at high doses over long period: risk kidney damage • Toxic doses: nausea and vomiting, fatal liver damage

NSAID side effects

• GI disturbances • Skin reactions

what is involved in assessing pain

• How severe is the pain- expressions can give an indication of pain? - What is the pain score? - How is the pain affecting the patient? • What type of pain is it? - Acute or chronic? - Cancer or non-cancer? - Nociceptive or neuropathic? • Are there other factors? - Physical e.g. what activities is it stopping them from doing relates to the treatment they will want - Psychological?

action of aspirin

• Irreversible inactivation of COX-1/2 enzyme has to be resynthesised

methods of taking cocaine

• Leaves chewed in Peru etc, cocaine hydrochloride • Snorted (hydrochloride; can cause perforation of nasal septum), or smoked with tobacco

describe pathological pain

• Maladaptive- pain itself the underlying pathological process • Results from abnormal functioning of the nervous system • Disease states caused by damage to the nervous system (neuropathic pain) or by its abnormal function (dysfunctional pain)- both are a result of damage to the CNS.

neurophysiology of Abeta fibres

• Myelinated fibres • Fast conduction velocity • Terminate in intermediate lamina (III-IV) of the dorsal horn • Glutamate transmitter, non-painful transmission • Responses sensitive to Glutamate receptor (AMPA receptor) antagonists

what is the plasticity of spinal responses

• Neuronal responses to repeated stimulation of C-fibres are not fixed and are not always proportional to the intensity of the stimulus applied • Enhanced responses (facilitated response, called wind up) for a given noxious stimulus are associated with repeated higher (0.5Hz) stimulation • Spinal neurones are sensitised to the noxious stimulus- called central sensitisation ability to facilitate altered response explains sustained sensation in patients with chronic pain

describe the antipyretic action of NSAIDs

• Normal body temperature regulated by hypothalamus • Fever due to disturbance in hypothalamic thermostat • NSAIDs reset thermostat due to inhibition of prostaglandin production, in hypothalamus • Temperature regulating mechanisms reduce temperature

describe inflammatory pain

• Obvious tissue injury or illness • Associated with tissue damage and infiltration of immune cells (acute inflammatory response)- promotes repair by causing pain hypersensitivity, until healing occurs • Protective response • Descriptors - Sharp and/or dull - Aching - Throbbing • Well localized- only affect area of tissue damage • May be secondary hyperalgesia around the area of the wound, but tends to be relatively small

describe the analgesic action of NSAIDs

• Pain associated with inflammation / tissue damage • Reduce inflammation (oedema and vasodilation) which causes pain

describe chronic pain

• Pain lasting for more than 3 months • Pain lasting after normal healing • Sometimes no identifiable cause • May be no obvious pathologic process • Intensity unrelated to tissue injury • Unpredictable time course- 2 days or several weeks • Difficult to treat

describe acute pain

• Pain of recent onset and probable limited duration- no longer than 3 months • Obvious tissue injury (e.g. injury, operation, burn) • Varying severity • Intensity related to extent of injury • Predictable time course • Treatments usually successful

Taking a Pain History

• Precipitating/Alleviating Factors: - What causes the pain? What aggravates it? What makes it better? Has medication or treatment worked in the past? • Quality of Pain: - Ask the patient to describe the pain, by suggestion 1/2 words using words like "sharp", dull, stabbing, burning" • Radiation- neuropathic, myofascial (muscular) pain - Does pain exist in one location or radiate to other areas? • Severity - Have patient use a descriptive, numeric or visual scale to rate the severity of pain. • Timing (rhythm) - Is the pain constant or intermittent, when did it begin, and does it pulsate or have a rhythm

what is involved in treating pain

• What non-pharmacological treatments can I use? • What pharmacological treatments can I use?

definition of anaesthesia

• Provision of insensibility to pain during surgical, obstetric, therapeutic and diagnostic procedures • Involves monitoring and restoration of homeostasis during the postoperative period • Requires application of pharmacology, pathophysiology and biotechnology

onset/ duration of effect for different opioids

• Route of administration / formulation • Not important for continual analgesia but essential for as needed-basis of treatment • Intravenous-2 min. average for most opioids • Intramuscular- lipophilic drug: 20 min. • Oral - normal release 1 hour - sustained 2-4 hours

transmissio of pain signals

• Signal arrives from periphery and travels into top of spinal cord, dorsal horn. • Synapse in the dorsal column nuclei • From the dorsal horn, the signals are integrated and then the message crosses to the contralateral side and travels to the higher brain centres. • Pain tracks cross at the level of the spinal cord

examples of ascending pain pathways

• Spinothalamic tract (STT) from Laminae I and V to the thalamus (blue)- spacial discriminatory pathway • Post-synaptic dorsal column (PSDC) pathway • Spinoreticular tract (SRT) • Spinomesencephalic pathway

the ideal inhalation anaesthetic

• Stable over range of temperatures • Not degraded by light • Odourless- don't want to educe the gag-reflex • Analgesic, anti-emetic and muscle relaxation properties- don't want mm twitching in surgery • Minimal respiratory depression • Minimal cardiovascular effects • Is excreted completely by the respiratory system • Not metabolised or no active metabolites

describe (dys)functional pain

• Substantial pain but no noxious stimulus and no, or minimal, peripheral inflammatory pathology- associated with function of nervous system • No neuronal damage (i.e. functional problem) • treatments are only successful for a small proportion of people- need to change mindset of patient and thus, use of psychological-based treatments • Conditions include: fibromyalgia, irritable bowel syndrome, tension type headache, temporomandibular joint disease, interstitial cystitis

describe acute non-cancer pain

• Symptom of tissue injury or illness • Usually nociceptive or inflammatory • Occasionally neuropathic e.g. sciatica due to compression of nerves

issues with aspirin used in the long-term

• Therapeutic doses gastric bleeding (5/6mls blood loss) (Yr 2 AS lectures) • Anti-platelet function (prevents heart attacks) • large doses: dizziness, deafness and tinnitus • toxic doses: uncompensated respiratory acidosis, metabolic acidosis • 2nd highest cause of gastric ulcers • epidemiological link with encephalitis if given to children with viral infection

neurophysiology of C-fibres

• Unmyelinated fibres • Slower conduction velocity • Terminate in superficial lamina (I-II) of the dorsal horn • Release peptides e.g. substance P • Responses sensitive to Glutamate receptor (AMPA and NMDA receptor) and peptide receptor antagonists

types of Uni-dimensional pain assessment scales

• Visual analogue scale (VAS) • Numerical rating scale (NRS)- 0 is no pain, 10 is the worst pain imaginable • Verbal rating scale (VRS)- using a range of verbal descriptors e.g. mild, moderate, severe

describe the second stage of the depth of anaesthesia

• cortical inhibitory centres depressed • increased muscle tone • vomiting- give an antiemetic agent pre anaesthetic dose to prevent vomiting • temperature control lost due to effects on hypothalamus- patient kept on heating blanket/ pad, prevent suffering of hypothermia • a-rhythm of EEG desynchronised • respiration increased / irregular

describe the fourth stage of the depth of anaesthesia

• loss of respiration • EEG waves leads to small which is lost • death

describe the first stage of the depth of anaesthesia

• reduction higher cortical function • consciousness not lost - but thoughts blurred • reflexes present • smell and pain lost at end of this stage

describe the third stage of the depth of anaesthesia

• slow synchronised EEG rhythms • regular slow breathing • medullary centres depressed • reflexes lost • pupils dilated and so are sensitive to light

clinical examples of the use of local anaesthetics

• topical - nasal mucosa and wound margins • infiltration - vicinity of peripheral nerve endings and major nerve trunks in dental practice • regional - intravenous injection leading to numbing of a larger area of the body in labour/childbirth