Pain

Are the following excitatory or inhibitory? TrkB mGluR, NK-1, AMPA, NMDA

Excitatory

What is the best way to decrease the degree of patient unpleasantness?

Explaining everything beforehand.

T/F The combination of depression and pain is not associated with worse clinical outcomes than either condition alone.

FALSE.

T/F While the majority of nociceptors have unmyelinated axons not all unmyelinated axons belong to nociceptors.

TRUE. The professor emphasized this point, so read it again.

Outside the brain, where is the largest collection of nocioceptors?

Dental Pulp

What is one way we express out emotions?

Body Language.

What is axon reflex?

"Activation of one branch of a nociceptor by a noxious stimulus results in the antidromic invasion of action potentials into adjacent branches of the nociceptor, which in turn causes the release of vasoactive substances from the terminals of the nociceptor."

What is spinothalamic tract (STT)

"Axons bundled in the anterolateral part of the spinal cord relaying somatic nociceptive and thermoreceptive information to brain The STT carries information originating from the opposite side of the body, i.e., is a crossed pathway.

What is the dorsal root reflex?

"If depolarization of primary afferents at the central terminals are large enough, it can generate the action potentials at the central terminals that are conducted antidromically in the primary afferent fibers, also resulting in the release of vasoactive substances from the nociceptor terminals."

What two terms were found to be statistically associated with pain from cardiac origin?

"Pressure" and "Burning"

What two terms indicate and odontogenic cause?

"Throbbing" and "Aching"

Other nociceptors respond to none of these modalities under normal condition but they may respond to stimulation under conditions of inflammation. These nociceptors are called?

'sleeping' or 'silent' nociceptors. Following injury or information, these sleeping or silent nocioceptors awaken and become responsive to previously ineffective stimuli.

Describe the level of "Nuisance" of the spectrum of orofacial pain diseases and disorders.

- Aggitates me throughout the day and then goes away and I go to bed - You don't really seek care, you don't really see a doctor, or take meds - "I can deal with it, it will eventually disappear"

Describe the level of "Seeking Advice" of the spectrum of orofacial pain diseases and disorders.

- Many people can handle pain with out treatment if they can understand it, sometimes this helps them deal with it. - Sometimes there are dangers attached to treatments ○ Person feels like they can handle the pain and not get the treatment = May be sufficient

What are the two types of chemical receptors?

Ionotropic receptors and Metabotropic receptors.

Describe the level of "Searching for cures" of the spectrum of orofacial pain diseases and disorders.

- These are patients that come, Dr. you have to do something right now, I cant take the pain anymore ○ That pain Is not something that just happened, it could have started a year ago, it could be different things ○ If you see that the patient had been to 42 different dentists before you, then maybe you will not be able to help them ○ It's the management of a pain condition that you bring a person back to life by allowing them to do things that they could not do before due to pain

Describe the level of "Seking Care" of the spectrum of orofacial pain diseases and disorders.

- This is affecting the person more than that they can handle - Pulls, muscles, tooth aches, Arthritis patients - they look for cures to take the pain away but the conditions come and go, can have periods of worse and less pain

Describe the level of "Devastating Pain" of the spectrum of orofacial pain diseases and disorders.

- We will not see many of these - They perceive lies about pain ○ They do not want to see a provider anymore about the pain ○ You will not see them because they do not believe us § They have had so many hopes and the hopes have never been met

What are some important characteristics of unmyelinated fibers with respect to nocioception?

-C-fibers -Smallest axons (diameter 0.3 - 1.3 micrometers) -Slowest conduction velocities (<2.5 m/sec) -Makes up about ~70% of all nociceptors

Analgesia?

Absence of pain in response to stimulation which would normally be painful

Darwin described the body expressions associated with emotions in animals and humans, with a particular emphasis on the link between what two things and what does that mean for the idea of phylogenetic history?

-emotion and action He highlighted the roots of facial expressions in adaptive actions. So, a species' ability to produce and perceive some basic categories of emotional body language is an integral part of its phylogenetic history.

What are some important characteristics of myelinated fibers with respect to nocioception?

-mostly A-delta fibers. -thinly myelinated (diameter <6 micrometers) -Intermediate conduction velocities (<30 m/sec) -makes up about ~30% of all nociceptors

What is a Noxious Stimulus?

It is an actually or potentially tissue-damaging event where the nervous system responds to warn the body of this exposure to something dangerous.

What parts of the brain are involved in emotions?

-pink = pain areas modulated by emotions [para-central lobule, medial, ventral prefrontal cortex, amygdala, thalamus] -Blue= effectors of emotions of pain [insula, dorsal lateral prefrontal cortex, orbital frontal cortex] Bs, brainstem; Rins, right insula; SMA, supplementary motor area.

Pain is not simply a sensation generated by nociceptors, but a?

...perceptual phenomenon with particular emotional qualities.

What are the 4 Mechanisms of Nociceptor Sensitization and the agents related to them?

1) Direct actions on excitatory ion channels; substances engage directly in the ion channels and change ability of nociceptors: ATP, glutamate and protons 2) Phospholipase C (PLC)-coupled receptors; Second messanger pathways: bradykinin, ATP, and NGF 3) Adenylyl cyclase (AC)-coupled receptors: prostanoids, 5-HT, cannabinoids and opiates 4) Mitogen-activated protein kinase (MAPK) pathways

Our professor spent a lot of time on the gate control theory. Lets look at it again from a more detailed look.

1) Proposed that large fibers activated a group of nerves in spinal dorsal horn or the comparable area in the brain stem for information for the face/mouth in trigeminal; large fibers when activated activate the substantia gelatinosa; large fibers will produce inhibition of small fibers so that if you relatively activate the large fibers than small fibers, you would reduce pain; you would suppress small fiber activation; greater activation of small fibers = producing an increase activation of pain. 2) When gate was open, more pain from small fibers, would result in pain perceived. 3) Substantia geatinosa would inhibit sensation, affect, and cognitive control perceptions of the brain. 4) They proposed (most innovative component) that there were central control systems to modulate the output of this t system into the nervous system; can be facilitatory and inhibitory. These systems are important in modulation in sensation and affective and cognitive components of pain.

What percentage of annual dental visits in the US are "walk-ins" or emergencies?

10.1%

How far into the dentin do nerves go?

100-200 micrometers.

Each ganglion contains how many neurons?

7,000-25,000 neurons.

Generally speaking, a nocioceptor has a diameter of?

<30 microns

In regards to Primary Afferent Nociceptor Signaling, what is activation?

Activation is a process involving membrane depolarization leading to action potential generation in the primary afferent nociceptor.

What is Central sensitization?

Activity dependent ( or independent) increase in synaptic efficiency in the spinal cord. Cells become hyperexcitable such that a given input will produce a greater output.

What is a very commonly seen dental pain that may be due to oversealous and severe tooth brushing?

Dentin Hypersensitivity to brushing and cold/hot foods. Commonly found on the opposite side of dominant hand. (right handed, left sided hypersensitivity.)

What is transduction?

A conversion of energy from the environment to a generator potential. Sensitization can involve the modulation of transduction machineries- e.g. injury or inflammation can alter the gating properties of TRPV1 , such as lowering the temperature required for activation.

Which projects more superficially a delta or c fibers?

A delta project typically to lamina 1

What leads to a more unpleasant pain experience?

A more intense noxious stimulus.

Tell me three definitions of a nocioceptor.

A receptor preferentially sensitive to a noxious stimulus or a stimulus that would become noxious if prolonged. A specialized class of primary afferent neurons that respond to intense noxious stimuli. Nocioceptors are some kind of receptor proteins that are expressed on nerve terminals such as acetylcholine receptors on neuromuscular junction. But when the professor says receptor here, he is not talking about a specific transducing molecule that is expressed in nerve terminals, he is talking about a whole primary afferent neurons just like other somatosensory receptors like proprio- or mechanical receptors. Nocioceptors are whole primary afferent neurons.

What is a Nocioceptor?

A sensory receptor that is preferentially sensitive to noxious stimuli. It is a receptor of the skin, viscera, and muscles. It senses tissue damage and results in activation of signals going into the nervous system and results in the perception of pain.

What are the four results found in animal model experimentation?

A. Dorsal rhizotomy of injured nerve root does not reverse the hyperalgesia B. Nociceptors in uninjured nerve also show abnormal spontaneous activity. C. Pain inducing or transducing molecules are upregulated in DRG of uninjured nerve D. TTX-R Na channels are increased along the sciatic nerve.

What are the three responding neurons of visceral stimuli?

Abrupt, sustained and inhibited.

Nociceptors can be sensitized through MAPK (mitogen activated protein kinase) signaling pathway. How does this signaling pathway occur?

After injury/inflammation, there is released nerve growth factor, which is binded to track A receptor and it's transported back into the cell body where nerve growth factor is then internalized and binds to p38 (MAPK). Upon phosphorylation of p38, it increases TRPV1 expression. Much more TRPV1 made and transported back out into the terminals, promoting thermal sensitization simply by an increased number of TRPV1 receptors on peripheral terminals.

Patients presenting with asymmetry in the face due to swelling usually have what?

An acute endodontic infection.

What is Pain catastrostrophising?

An exaggerated negative mental set brought to bear during actual or anticipated pain experience"

Describe the sensory interaction theory.

An important contribution to summation theory was the concept of sensory interaction shown in C and proposed by Norrdenbos in 1959. He proposed that large rapidly conducting myelinated fibers that ordinarily signaled touch, could suppress activity in small fiber pathways that convey noxious or painful information. A decrease in the ratio of large to small fibers would result in central summation and more pain. An increase in the ratio of large to small fibers will results in suppression or inhibition of the pathway signaling pain and a decrease in pain. The sensory interaction theory stressed inhibition, another important physiological mechanism in nociceptive pathways. IMAGE FIGURE C

Hyperalgesia, again, is?

An increased response to a stimulus which is normally painful.

What is Hyperalgesia?

An increased response to a stimulus which is normally painful. Hyperalgesia refers to the augmented response to a specific modality, pain. It reflects increased pain on suprathreshold stimulation. It should be recognized that with hyperalgesia the stimulus and response are in the same mode whereas in allodynia the stimulus and response are in different modes.

So then, what is Pain?

An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. There is a *sensory* and *emotional* component, or a memory and cognitive component of pain. The memory of something may be described in terms of damage but there may not be tissue or nerve damage present.

What is a systemic disease that causes referred oral pain?

Anginal Pain. Heart attacks make you think you have a toothache.

How was wind- up affected when animals took ketamine?

Animals had a decrease of wind-up, by the time you get to 50micrograms there is no wind-up at all.

Which part of the brain is involved in motoric and motivational aspects of pain and emotions?

Anterior Cingulate Cortex

What is the difference between Axis I and Axis II of clinical presentation?

Axis I = Physical Dimension Axis II = Mood and Pain Related Disability

What is the trigemothalamic tract (TTT)

Axons relaying all types of sensory information from the trigeminal nucleus to the thalamus, note differential termination of nociceptive vs. mechanoreceptive afferent fibers within the trigeminal nucleus.

Why are the Dorsal Root Ganglia also called psuedounipolar?

Because they initially develop as bipolar neurons.

Why are visceral afferents not suceptible to somatotopy?

Because visceral nerves from one spinal nerves can spread over 10 segments in the cord.

First statement, T/F, second statement, T/F. "Opioids are effective analgesics for both somatic and neuropathic pain; but they are usually inadequate to control moderate to severe pain."

Both True.

Take a student ( Geoff) and give him repetitive acute pain over and over again as you do this this there is an increase response to a fiber input due to wind-up which fiber increased in response? Adelta or C-fiber?

C-fiber. ( Quantitatively there is an increase in responsevof the cell over time, to the same stimulus, but repetitively. There is no change in NT release, it is a change in response of the DHN that is called wind-up. As soon as you stop stimulation, the excitation goes away along with wind-up)

Why are comorbidities important when it comes to pain?

Depression, for example, reduces the range of intellectual function. Do people with depression have pain? or do people with pain have depression? Two studies have shown: 69% of patients that were having depression also had pain. Another study had 51% of those that had depression also had pain If you have both pain and depression the pain and disability goes up, and the use of healthcare goes higher

When the axons from an intact nerve are in close proximity to the degenerating nerve, what are the intact nerve fibers exposed to?

Diffusible substances that are released from the dying nerve.

Noxious distention, swelling, or pressure can activate receptors in two diff mechanisms. What are they and describe them?

Direct and indirect. Direct: stimuli may activate a molecular transducer that is gated by a mechanical stimulus, so a conformational change produced by noxious stimulus may open channel allowing influx of cations like calcium and sodium. But until today, such molecular transducer has not been experimentally demonstrated. Indirect: Pressure/distention/swelling of local tissue may cause release of some chemical mediators that can act on nearby nocioceptors and by activating thru certain receptors that can transduce noxious mechanical stimuli into electrical effect.

What kind of neurons neurons are unipolar neurons that project bifurcated axons to both peripherally and centrally

Dorsal Root Ganglia

Cell bodies lie densely packed w/in ganglia wrapped around by connective tissue called?

Dura Mater.

What are first and second pain?

Early investigations reported that noxious stimuli applied to the extremities elicited in humans an experience of two distinct sensations: an early stinging, sharp, well-localized sensation followed about one second later by a diffuse, burning sensation that outlasted the stimulus. These were called first and second pain. It is now known that these sensations correlate with conduction in finely myelinated nerve fibers (A delta fibers) and unmyelinated C fibers. Block myelinated, only perceive 2nd pain Block unmyelinated, only perceive 1st pain.

Is emotion related to reasoning?

Emotion, far from being a biological oddity, is actually an integral part of cognition(our reasoning)

What is a multidimensional phenomenon?

Emotion.

What is Darwin's view of emotions?

Emotions are adaptive in the sense that they prompt an action that is beneficial to the organism, given its environmental circumstances. Emotions are vital and are actually adaptive. Emotions are neurobiological and cant be dismissed. Depression, for example, is a strong component that can influence pain .

What is the Cartesian view of emotions?

Emotions are private mental episodes. However, they are not this. they are processed within our physical bodies.

What is the best way to help a patient in pain?

Especially with persistent pain and how unique it is, the best thing to do is to listen to your patient.

T/F Activation always leads to sensitization and sensitization cannot occur without nociceptor activation.

FALSE. Activation does not always lead to sensitization and sensitization can occur without nociceptor activation.

T/F A variety of chemical mediators from neuronal and non-neuronal cells cannot activate nociceptors by binding to specific receptors.

FALSE. They can. If there is damage to tissue/injury, a whole variety of chemical mediators are released form neurons and non-neuronal cells; and these analgesic substances/pain producing substances can activate nocioceptors by binding specific to their receptors.

T/F Central sensitization does not result from an increase in excitabilty of dorsal horn neurons. Central sensitization underlies hyper algesia and allodynia that occures away from the site injury

False / True

T/F Boys experience pain from the body before girls.

False. Girls tend to experience pain earlier shown by earlier onset of puberty. Girls also tend to experience depression first as well.

T/F Substance P is not involved in wind-up

False. Substance P is involved. Substance P is released and binds its metabotropic receptor (NK-1), causing formation of IP3 that goes and binds to a receptor on the ER that increases calcium release in the cell and increases intracellular calcium

What condition will make a patient think they have oral pain even after odontogenic treatment?

Fibromyalgia

First statement, T/F, second statement, T/F. "There is no strong evidence that tricyclic antidepressants are analgesic in my types of pain; but they are usually inadequate to control moderate to severe pain."

First false- there IS strong evidence; second true.

White fibers carry first pain and second pain?

First pain is carried by A-delta fibers while second pain is carried by C fibers

What is first pain? What fiber is associated with it?

First pain is the instantaneous perception you get when you get the prick; this is mediated by A-delta fibers that conduct faster ( myelinated, larger); this is usually described as sharp pain.

First statement, T/F, second statement, T/F. "NSAIDs and acetaminophen are effective for reducing the intensity of chronic pain; but they are usually adequate to control moderate to severe pain."

First true, second false. they are usually INADEQUATE.

What are inhibitory transmiters used in interneurons?

GABA, glycine, and enkephalin

What does glutamate exposure do to neurons in a test of thermal stimuli?

Glutamate exposure increases sensitization of neurons. The firing rate increases and the number of action potential increases.

Describe the mechanism of summation.

If one blocks the A fibers(myelinated) one finds that the response to pain increases with successive stimuli. Studies shows that pain summates with repeated stimulation.

Harder pinch on the previous card

If you give a harder pinch, you get peripheral sensitization and primary hyperalgesia. You get some swelling, redness, release of inflammatory mediators... This sensitizes the primary afferent and you get a greater response out of it it and maybe even some spontaneous activity in the afferent. All this converges on the dorsal horn.

What is the first stage of the Affective Component of Pain?

Immediate Affective Response to a Noxious Stimulus Or, Acute Pain.

There is a pair of ganglia that is laterally associated with each vertebra from the cervical to sacral levels. Where are the primary afferent neurons of these nocioreceptors found?

In the Dorsal Root Ganglia (DRG) or the spinal ganglia.

What is wind-up?

Increased response and output of DHN due to repetitive stimulus.

In patients with congenital insensitivity to pain, C fibers are absent in the peripheral nerves, indicating what?

Indicating c-fibers are needed in perception of pain.

Tell me about the features of fMRI

Indirect measure of neural activity, Non-invasive, Largely available technology, Good spatial resolution (~1cm3), Ok temporal resolution ( Seconds), Unlimited replications, can evoke claustropobia

What is pericoronitis?

Inflammation around erupting tooth. Sometimes due to lack of erupting space, can't erupt into surrounding space. Means they are partially erupted.

Describe Inflammatory Hyperalgesia.

Inflammatory pain is pain occurring associated with inflammation of the tissues. It is damage to tissue resulting in hyperalgesia and allodynia.

Which area in the thoracic spinal cord houses the neurons of the sympathetic system?

Interomediolateral nucleus (IML)

What is the role of the insula in emotions?

Involved in thought to generate subjective interoceptive feelings .

What are the two types of receptors on the nerve synapses?

Ionotropic (ion channels) and metabotropic (eg. G-protein signalling)

What is an ionotropic receptor?

Ionotropic receptors have ligand- gated channels and are an integral part of the ion channel that it regulates; ligand binding changes channel gating (ATP, H+, glutamate, etc) The receptor and channel are one.

Which are ionotropic and which metabotropic?

Ionotropic: AMPA, NMDA, GABAa. Metabotropic:mGluR, NK1, GABAb, Opiod (OR)

How does bradykinin induce nociceptors?

It binds and activates G-protein. When a substance binds to the G protein, it dissociates the G protein, which goes off to activate phospholipase C (PLC); This then activates PEP2, breaks into DAG (releasing PKC) and IP3 (which releases Ca2+ ions from intercellular stores). This activates Protein Kinase C (PKC); PKC phosphorylates TRPV1 channel and lowers activation of TRPV1. So bradykinin induces sensitization through enzyme activation of PKC.

Describe the gate-control theory that Melzack and Wall proposed.

It combines the strengths of previous theories and presents new hypotheses. The basic tenets of the theory are:1) nerve impulses from peripheral nerve fibers to the spinal cord are modulated by a spinal cord gating mechanism. The "gate" refers to the relative amount of inhibition or facilitation that modulates the activity of the T or transmission cells carrying information about noxious stimuli to higher centers of the brain. 2) The gating mechanism is influenced by the relative activity in large diameter (L) fibers activated by nonnoxious stimuli and small-diameter (S) fibers usually activated by intense, noxious stimuli. Thus the theory recognized specialized fibers activated by noxious stimuli, and mechanisms of convergence and summation. 3 and 4) The gating mechanism is influenced by central control mechanisms from the brain that relate to cognitive, attentional and motivational processes. 5) When the output of the T cells exceeds a critical level, neural systems are activated that underlie complex behaviors or action systems related to escape and avoidance behavior.

How has our understanding of Glial cells changed in regards to pain?

It has shifted from house keeping cells to integral components of neuronal signaling. In the dorsal horn they are linked to the development of neuropathic pain.

What does bradykinin alone do to a neuronal response to a stimuli?

It produces action potential generation with a certain impulse rate.

Tell me everything you know about the specificity theory proposed by von Frey.

It states that each sensory modality has its own peripheral and central nervous system neural apparatus so that stimulation leads to activation of a selective, immutable pathway. E.g. different types of receptors and fibers that carry information related to different senses: (Touch / mechanoreceptors, Nocioceptors /pain) These pathways were maintained throughout nervous system; info ultimately reaches cerebral cortex and pain is elaborated. These pathways were related to individual pathways. This theory is wrong. There are specialized receptors in the skin, muscles, viscera, but the receptors transfer info that can be modulated on different levels of the nervous system. IMAGE FIGURE A

Is A-beta an example of an LT, WDR or NS neuron?

LT. It doesn't convey pain.

Where are LT neurons most numerous?

Laminae 3,4,5

In which lamina is the somatotopy most prominent?

Laminas 1 and 2

Which laminas are key to the spinothalamic tract?

Laminas 1,5,6

How about a beta fibers (which lamina?)?

Laminas 3,4,5,6

What is responsible for discriminative aspects of touch, and to some extent, temperature and pain senses ( Discriminating sensory qualities, Intensity of stimulation, Localizing stimulation, Temporal features of stimulation.)

Lateral thalamus: Majro projections to the cerebral cortex [ VPL,VPM --> S1 and S2 cortex]

Ascending Nociceptive pathways

Lateral thalamus: The Venteroproteriolateral (VPL) nucleus recieves STT and mdial leminscal input, the Ventroposteriomedial (VPM) nucleus receives TTT input. Thus VPL and VPM receive both innocuous and nociceptive signals. Ventro posterioinferior (VPI nucleus. Receives principally ( exlusively?) nociceptive and thermoreceptive signals.

If I put a lesion is Geoff's S1 cortex what would the the outcome be?

Lesions in S1 cortex always alter tactile perception, rarely affects pain perception.

If I put a lesion in Geoff's S2 cortex what would happen?

Lesions in the S2 cortex frequently alter pain and temperature perception, often affect tactile perception. ( The same is noted for VPL/VPM/VPI lesions.

What are some ways to evaluate human brain function?

Lesions, as well as neuro imagine ( PET, fMRI, EEG, MEG)

In what way are protons associated with sensitization?

Low pH solutions have been shown to activate nociceptors in cutaneous tissues.

What are some things included in the inflammatory mixture?

bradykinins, cytokines, prostaglandins.

What area of the brain is responsible for affective and motivational aspects of pain?

Medial dosal nucleus - Ventral caudal part (MDvc) Projects to anterior cingulate cortex, as well as with the rest of the limbic system.

What is a metabotropic receptor?

Metabotropic receptors indirectly regulate the channels; the receptor is distinct from the ion channel it regulates; ligand binding activates second messenger cascades that alter channel gating (Bradykinin, prostaglandin, substance p, etc) One or more metabolic processes are involved in changing channel properties.

The NDMA receptor is blocked by which of the following? Mg2+,Fe2+,Ca2+,Na+,K+

Mg2+

Activity of A-delta nociceptors correlates well with psychophysical data. What kind of studies have supported this idea?

Microneurographic studies support the role of a-delta fibers. Selective block experiments (loss of pain sensitivity), also confirm a-delta fibers are also required. You can see in this final figure that as the stimulus falls, mechanical stimulus increases, pain ratings increase following the selective blockade of a-delta fibers with ischemic block, and sensitivity is significantly deteriorated, which suggests a-delta input is required for the perception of pain.

What are some more common painful conditions?

Mucositis- variety of conditions that can lead to bullous formation and these can be quite painful. Many are chronic conditions. Burning tongue- condition that affects some patients. May be related to hormonal changes. May be a microbial relationship. Etiology not quite clear. It is a condition that is chronic and lasts for long time. Patients must learn how to manage and deal with it.

What are the two types of afferent fibers found in nocioception?

Myelinated and unmyelinated.

So do the a-delta or c-fibers of nocioception have morphologically specialized receptors?

NO.

What are some peptide sensitizing agents that sensitize the nociceptors?

NOTE: Eicosonoids = prostaglandins There are also pain-reducing and analgesic substances released in the peripheral terminals as well (opioids released by immune cells recruited to injury site; cannabinoid receptors reduce pain and reverse sensitization process)

What is resting membrane potential of a dorsal horn neuron?

Negative 70mv

Describe Neuropathic Hyperalgesia.

Neuropathic pain refers to pain produced by injury or disease to the nervous system. It is a result of damage to the nervous system or somatosensory component of the nervous system.

Do nerve endings reach the dentin surface and cause pain?

No. What seems to be causing pain is not nerve endings directly, but movement of fluid, stimulating nerve endings at pulpal ends of tubules. Nerve endings do not go very far into tubules. If you apply any osmotic change to dentinal tubules, there is stimulation of nerve endings at other end.

Is it true that women are weaker than men?

No. Women have two forms of pain, menstrual and labor. Their brains are wired differently and have to overcome the fear of pain such as having a 2nd child. There is a mechanism that makes a women forget that she is willing to do it one more time.

What are the three types of pain?

Nociceptive Inflammatory hyperalgesia Neuropathic hyperalgesia

Describe nocioceptive pain.

Nociceptive pain refers to the normal activation of the components of the peripheral and central nervous system by an intensive stimulus that leads to the perception of pain. Pain produced by a pinprick or the touching of a hot stove are examples of nociceptive pain. It is transient and produces no damage to the body.

What happens when bradykinin in injected into the body?

Nociceptor at first was not responsive to innocuous stimulus, but it was activated by noxious stimulus. Muscle contraction and stretch don't activate this cell.Then, the bradykinin injection did activate the cell and cause innocuous stimuli(mechanical only) to be painful. This neuron was activated and sensitized by bradykinin.

Are small caries usually painful?

Nope. Caries have to be very large to be painful.

What are some common painful conditions?

Odontogenic- arising from the tooth or surrounding structures. Ulceration - anytime there is a break in the surface epithelium.

What are two psychological variables that affect pain?

Odor and Pictorial scenes. Odors can intensify pain more unpleasant or pleasant. Olfaction is in the processing part of brain that can interact with the superior spinal and descending pathways of pain. The pictorial part deals with the effective part of pain, not intensity.

What are the two places that a spinal cord interneuron can act?

On the presyaptic terminal of the primary afferent or on thedorsal horn neuron itself.

What happens if prostaglandins and opioids are present at the same time?

Opioid peptides/endorphins and cannabinoid are also expressed. These G-protein coupled receptors are associated with G-proteins (called Gi proteins). When cannabinoids are activated, it associates with a Gi protein and DECREASES the amount of adenylyl cyclase and blocks PKA. Therefore, if prostaglandins and opioids are present at the same time, the TTX-resistant channels will be blocked by cannabinoid or opioid receptors.

T/F Pain is personal and so are pain-related activation

TRUE

Where are those nerves located within the pulp?

Other nerves include autonomic, mostly sympathetic, and they are in walls of blood vessels in dental pulp

When directly acting on excitatory ion channels, what cationic non-selective ion channels does ATP alter? What occurs when these cells are activated by ATP?

P2X3; Activation of these depolarizes the cells and increase excitability of the cells. Increase in excitability contributes to sensitization.

What is Neuropathic Pain?

Pain arising as a direct consequence of a lesion or dysfunction affecting the somatosensory system.

What is Allodynia?

Pain due to a stimulus that does not normally provoke pain. The term involves a change in the quality of the sensation whether tactile, thermal or any other sensory quality. The original modality is normally non-painful but the response is painful. Example: Showering after a sun burn.

Allodynia?

Pain due to a stimulus which does not normally provoke pain

What is neuropathic pain?

Pain initiated or caused by a primary lesion or dysfunction in the nervous system.

Persistent pain associated with inflammation or nerve injury has many special signs and symptoms that are not associated with the normal nociceptive pathways that transmit information related to injury. What are the clinical feature of persistent pain?

Pain occurs in the absence of detectable tissue damage Pain in a region of sensory deficit Mild stimuli are painful (allodynia) Intense stimuli produce more pain (hyperalgesia) Summation with repetitive stimuli Delay in onset after injury Abnormal unpleasant sensations (dysesthesias)

What reduces the range of motion of the body?

Pain. You limit the range of function to what you allow yourself to do without pain.

What area of emotions are periodontists lacking knowledge?

Periodontists were less knowledgeable about the impact of depression on patients' responses to the treatment.

Sensitization can be observed in what kind of neurons?

Peripheral and central neurons.

What happens following injury?

Peripheral sensitization --> primary hyperalgesia ( Decrease threshold, Increase suprathreshold response, Spontaneous pain)

Why do patients with chronic pain tend to like dentists better?

Physicians have too fast of a schedule and dentists find more time for the patient and can relieve oral pain.

What is a Primary Afferent Nociceptor (PAN) ?

Primary Afferent Nociceptor (PAN) - First order sensory neuron that is activated by noxious or potentially tissue damaging stimuli.

T/F fasciculus gracilis recieves from the sacral and lumbar segments.

TRUE (fasciculus cuneatus recieves fibers from the thoracic and cervical segments)

Some inflammatory mediators sensitize nociceptors by increasing intracellular Adenylyl Cyclase levels. What kind of mediator does this and how?

Prostaglandins. When prostaglandin binds to prostaglandin receptors, it's associated with another type of G-protein, which activates adenylyl cyclase, which goes to activate PKA.

How do protons cause the sensitization of a TRPV1 receptor?

Protons can function as a proton-allosteric modulator of a channel. Binding of a proton can lower the activation threshold of TRPV1. Local acidosis lowers nociceptor excitability and promotes sensitization through action of proton-binding on TRPV1.

What percentage of emergencies are for pulpitis? For acute periapial pain?

Pulpitis: 35% Acute periapical pain: 31%

Whats the basics of PET, not your dog skoo.

Quanitative determination of the location of Positron emitting isotopes. It is used to create a functional image map (Hence tomography) Frequently use heavy water H2[15]O - that measures oxygen metabolism.

When are women and men the most sensitive to pain?

Reproductive years.

You stub your little toe while walking down the stairs. Which segment of the spinal cord will be involved?

Sacral (this caries the back of the legs, butt, side of the feet and genitals. The lumbar serve the legs and hips. The thorasic serve the abdomen and lower 2/3 of the thorax, plus the medias aspect of the hand. The cerivacal serve the upper 1/3 thorax and the lateral and doral arms, plus the back of the head)

What is second pain, and the nerve fiber associated with it?

Second pain occurs a little bit after; sticking your finger with hot water takes a brief delay then you feel the sensation-this is due to C fibers (Smaller, unmyelinated) and is described as a burning sensation, rather than sharp and prickly

What interacts with the affective component of pain to predict depressive symptoms?

Self-criticism. Self-criticism is activated by the affective, but not sensory component of pain in leading to depressive symptoms. It affects the way pain is perceived. Those who scored higher on level of self-criticism had activated more affective parts of the brain.

What is the difference between sensitivity and hyperalgesia?

Sensitivity is NEURAL response (nocioceptor response) versus hyperalgesia which is a subject response.

In regards to Primary Afferent Nociceptor Signaling, what is sensitization?

Sensitization is a modulation of functional properties of the primary afferent nociceptor leading to a hyperexcitable state, which could result from modulation of cellular proteins leading to changes in ion channel activity with a subsequent increase in excitability.

What are the three demensions of pain and describe the differences between them.

Sensory-discriminative - What are the features of pain that the patient is receiving (quality of pain, how long it lasts, the intensity, location, etc.) Cognitive-evaluative - To the individual, what is meaning of pain of patient? Affective-motivational - How do you feel about the pain? Does it cause anxiety? Fear? Upsets us? Bothers us?

What are the two components of the experience of pain?

Sensory-discriminative and Affective-motivational They can be dissociated.

T/F Human judgments of pain to stimuli over the range of 41-49C correlate well with activity of CMH fibers in monkeys.

Shown in this graph is stimulus temperature and pain responses on one axis and monkey fiber responses on other axis. As temperature increases, human perception of pain increases; remarkable correlation of c-fiber activity recorded from monkey fibers that correlated really highly of perception of human pain, indirect evidence that c-fiber activity contribute to perception of pain. But we can argue, we cant compare that, were getting response form human subjects and comparing that to monkey fiber activity. CMH = C-fibers, mechano, heat

If a patient presents with an abscess, how do you determine if it is a periodontal or endodontic abscess?

Simplest way is to do a pulp test. You want to know if the dental pulp in any of these teeth is responsible for this abscess. If that's the case, its an endodontic abscess. If all teeth respond normally to pulp testing, and patient has attachment loss, more likely to be periodontal abscess and treatment will be periodontic not endodontic.

What are the two types of receptors based on response characteristics?

Slowly adapting nociceptors that exhibit sustained responses to a noxious stimulus. Rapidly adapting nociceptors that respond only at the onset of stimulation. These functionally different types of responses allow nociceptors to provide information about static and dynamic qualities of a stimulus.

T/F All nociceptors terminate in free nerve endings regardless of their myelination.

TRUE. Professor repeats the point, so read it again.

Sensitization can be described as a leftward shift in the stimulus response function that relates magnitude of neural responses to?

Stimulus intensity.

Give me an example of an indirect mechanical transduction.

Stretching and filling of the urinary bladder promotes release of ATP from epithelial cells and this ATP is known to activate nocioceptors that are embedded within epithelial tissue; ATP binds to P2X receptors which are also non-selective cationic channels; ATP binds to the channel and allows and influx of sodium and calcium, driving the depolarization of terminals.

What's the relationship between hyperalgesia and peripheral sensitization?

Studies show hyperalgesia results from sensitization.

How does this PKA cause sensitization of neurons?

Studies show that PKA can phosphorylate very interesting molecules called TTX resistant voltage-gated sodium-channels (important for generation of action potentials in ALL cells).Most cells are affected by TTX (toxin that blocks voltage-gated channel activities). There are a particular type called TTX-Resistant. They are NOT affected by TTX and these types can generate action potentials. When these channels are phosphorylated by PKA, they become easier to get excited and generate activation potentials much easier. PKA can cause sensitization in this way.

What is the area that can seconday hyperalgesia from central sensitization

Subliminal fringe

What is substance P and what does it do to the neurons response to stimuli?

Substance P Is an analgesic agent. Substance P produces an increase in background discharge; Substance P activates the cell, BUT it doesn't enhance the cell to subsequent mechanical stimulus. This is nocioception activation WITHOUT sensitization.

Where are NS neurons most numberous?

Superficial dorsal horn (1,2,) and laminae 5,6

TRPV1 is found in what kind of fibers, and is activated by what temperature and other stimuli?

TRPV1 (VR1) is found in C and A-delta fibers and is activated by moderate heat (~45 C) and by capsaicin.

What about TRPV2? What temperature stimulates it, and how does it compare to TRPV1? Where is it found?

TRPV2 (VRL1) has a higher threshold response to heat (52C), not sensitive to capsaicin, and found mainly in A-delta fibers.

Which doesn't cross the spinothalamic tract or the dorsal column?

The Spinothalamic does cross but the dorsal is ipsilateral.

Which spinal nucleus of the trigeminal nerve does nocicpetion usually go to?

The Vc of the Caudalis

What ability does somatotpy contriute to?

The ability to localize pain (this is poor in visceral nerves)

What are some important attributes for health care providers because these attributes contribute to health maintenance, including mental health, and career development?

The ability to perceive emotions in self and others, manage emotions, and handle relationships.

How do you assess the affective component of pain?

The amount of pain Unpleasantness.

How is the amygdala related to emotions?

The amygdala decodes the affective relevance of sensory inputs and initiates adaptive behaviors via its connections to the motor systems.

What are the dermatomes?

The area of the body innervated by afferents from a given segment.

So whats the main difference between axon reflex and dorsal root reflex?

The difference is that the depolarizing potential is not initiated at peripheral but at the central terminal. Whatever is happening here, if the depolarizing potential at the dorsal root is sufficient enough, it will conduct backward, antidromically to peripheral terminals and initiate the process that releases substances.

Wait, what is Antidromic invasion?

The direction of an Action Potential travelling towards the CNS is called orthodromic conduction because its going in the right way; as the AP is going along, it can invade nearby terminals; its not going into CNS but going back out into terminal so its called antidromic propagation. Antidromic invasion of an AP to nearby terminals causes some things to happen. When AP invades a nerve terminal, it depolarizes the nerve terminal, which opens voltage gated calcium channels and it flows in; calcium is required for the vesicular release of some substances that are stored within the terminal such as the release of calcium before the release of a NT in the CNS. When the depolarizing potential invasion of nerve terminal calcium ions flow in and cause release of CGRP(vasodilatory agent) or substance P (produce plasma extravasion) this leads to neurogenic inflammation.

What is Nocioception?

The neural processes of encoding and processing noxious stimuli. It is important to note that you can have nociception but still no pain. You may process a noxious stimulus but never reach the level of perception. Thus, not pain. You have to differentiate between nociception and pain.

What is the nomenclature that is used to describe deep tissue nerves such as joint/muscle nerves and what is it based on?

The nomenclature uses roman numerals like group I, II, III, IV fibers. This categorization is based on axon diameter.

What are the three division of the spinal nucleus of the trigeminal nerve (name them from superior-inferior)?

The oralis, interpolaris, and caudalis.

Tell me everything you know about the summation theory proposed by Goldscheider.

The summation theory in its most general form proposed that pain is not a separate modality but results from overstimulation of other sensations: very bright lights, very loud sounds, etc. Goldscheider proposed that excessive skin stimulation activated all types of receptors and pain resulted when activity exceeded a critical level. Its emphasis on convergence and summation was a valuable contribution to our understanding of pain mechanisms. IMAGE FIGURE B

Which two areas of the dorsal horn are important for nociceptive processing?

The superficial and deep dorsal horn laminae.

What happens to human reports of pain to a heat stimuli before and after a burn?

The threshold for pain is lowered and pain response to suprathreshold stimuli is enhanced.

Where is pain from the orofacial region processed?

The trigeminal nuclear complex

Where do the two branches of the DRG neurons terminate?

The two processes first branch out into peripheral tissues like joint, cutaneous, or muscle tissue and the second process is extended towards CNS (central processing) terminating in 2nd order neurons located in dorsal horn of spinal cord or spinal nucleus of trigeminal nerve in brain stem in the case of trigeminal system.

If people know that a noxious stimulus coming in, what do patients do?

Their degree of pain unpleasantness can be affected and influenced by their anxiety.

What are polymodal nocioceptors?

There are distinct classes of nociceptors that are exclusively responsive to each of those three specific stimulus modalities previously named. The vast majority of nocioceptors are responsive to two or more modalities, and many are responsive to all three. Those that are responsive to many modalities are called polymodal nocicepors (~70% of all nociceptors).

How do nociceptors transduce various physical and chemical stimuli into electrical events?

There are molecular transducers that transduce noxious thermal stimuli into electrical events; also ones that transduce noxious cold stimuli into electrical events; but we don't know so much about molecular transducers that transduce mechanical stimuli into electrical events; there are chemical receptors that respond to chemical mediators that activate nocioceptors.

Do nociceptors really signal pain in human?

There are multiple lines of evidence that support the role of nociceptors in human pain sensation.

What is the role of Intact Nociceptors when discussing hyperalgesia?

There is much evidence that nearby uninjured nerve fibers also contribute to neuropathic pain and hyperalgesia.

What was the pattern found when studying the electrical conductivity of skin between a therapist and patient?

There may not be any physical touching but the physiological levels seem to match up, showing there is an emotional link to the body.

What are the three modalities and types of receptors that nocioceptors are classified as?

Thermal - thermo-nociceptors Mechanical - mechano-nociceptors Chemical - chemo-nociceptors

Where are acid sensing ion channels expressed?

They are also expressed in small-diameter nociceptors. The mediated the actions of protons in nociceptor endings.

What are projection neurons?

They are different from interneurons because they will convey information into supraspinal sites.

What do feelings do to our bodies?

They motivate behavior and generate autonomic responses.

Nociceptors serve an efferent role, in addition to the afferent role. What do they do?

They release chemical mediators from their peripheral endings.

What does an inflammatory mixture do to neurons in a test of mechanical stimuli?

This nociceptor was originally unresponsive to a 5 bar (500kpa-50g/mm sq.) mechanical stimulus; Then,the inflammatory mixture vigorously activated the cell after its application; Then the cell was intensely activated by 5 bar stimulus 30 minutes after the application of inflammatory mediators.

Allodynia and hyperalgesia, usually to mechanical stimuli, are major characteristics of persistent pain following what?

Tissue or nerve injury. Normally, increases in noxious stimulation lead to increases in pain sensation in the range of tissue damage. It characterizes our behavioral response to transient pain. However, after persistent injury, this relationship often shifts to the left.

So, if the professor shows you a graph differentiating between type I and type II AMH receptors, can you interpret it?

Top 4 = type I Bottom 4 = type II Each response is 1 neuron, each tick is when stimulus fired. Top 4 traces (with differ in latency or onset of activity) show continued responses by firing action potentials when stimulus is maintained. In contrast, type II AMH shown in bottom 4 fires vigorously only at onset of stimulus and quiet out (rapidly adapting).

Geoff touched his hot plate in lab and quickly withdrew his hand. Explain how glutamate played a roll in this.

Touching the hot plate evoked a release of glutamate from the central terminal of primary afferent. Glutamate binds to AMPA/kainate receptors on dorsal horn neurons evoking a flexion reflex and bring sensation of pain. This fast synaptic processing provides the onset, duration, intensity and location of the noxious stimulus in the periphery.

A delta nociceptors can be classified into two types based on their responses to sustained stimuli. What are these two types and describe them, please.

Type I AMH - are slowly adapting, and they are "tuned" to detect the continued presence of noxious stimuli Type II AMH - are rapidly adapting, and they are "tuned" to detect changes in stimuli A = a-delta M = mechanical H = heat Responds to both mechanical and heat stimuli = polymodal receptor

What is the difference between transient and persistent pain?

Transient (acute) pain = protective (hand on hot pot) Persistent = lasts days to months (forces you to rest) Can become chronic and no longer protective when the injury has healed but the pain continues. Pain that lasts more than 3-6 months is considered chronic pain.

Where are the primary afferent neurons that innervated the craniofacial structures located?

Trigeminal Ganglion or Gasserian ganglia.

T/F Hyper algesia is an increase in pain from a mildy noxious stimulus; allodynia is the perception of pain from an innocuous stimulus.

True True

T/F Both warm-receptors and sympathetic efferents also have unmyelinated axons.

True.

T/F Carotid artery blockage can lead to oral pain

True.

T/F Nociceptors are able to convert energy from the environment into electrical signal; the energy can be thermal, mechanical or chemical.

True.

T/F Selective A-fiber (ischemic) or C-fiber (local anesthetic) block indicates C-fiber function is necessary for thermal pain sensation

True.

T/F The prevalences of pain in depressed cohorts and depression in pain cohorts are higher than when these conditions are individually examined.

True.

T/F Human perception of heat pain is shaped by composite responses from these nocioceptors.

True. Human perception of heat pain is shaped by composite responses of all different receptors. When a stimulus is applied, we appreciate the dynamic and static qualities of stimulus. And we have a composite pain reception response as combination of different types of nocioceptors.

T/F Nociceptor sensitization can be observed at multiple steps in afferent signaling process.

True. Nociception can happen at the transduction level (chemical and mechanical stimuli) and can also occur at initiation, propagation and release levels (see numbers in picture).

T/F Thermosensitive TRP channels respond to a wide range of temperatures.

True. TRP channels have been found to respond to temperature in different ranges, according to their temperature response profiles from noxious cold below 17 degrees to noxious heat. Together these TRP channels theoretically account for the detection of all the range of temperature we encounter in our daily lives. Importantly, each channels has been reported to be found in DRG or TG neurons, implicating their role in sensory function.

T/F Several inflammatory mediators sensitize nociceptors by activating PLC-coupled receptors.

True. These are G-protein coupled receptors (GPCR).

Can you describe the difference between hyperalgesia and analgesia based on a chart?

Under normal condition (black line), noxious stimulus produces certain level of pain response. Following insult to the system, there is a LEFT-ward shift of the curve, meaning that there is a greater level of pain. Previously innocuous stimulus is now producing pain (allodynia). Analgesia can be explained by the RIGHT-ward shift; a greater level of intensity is required to produce the expected pain response.

What is responsible for disciminative aspects of temperature and pain ( Less so for touch )

VPI -> S2 cortex ( Less so to S1 cortex)

Ascending visceral pathway

Visceral information (nociceptive or otherwise) ascends principally by way of the dorsal column post-synaptic neurons, whose axons run in the deep dorsal columns. The rest of the dorsal columns (you should remember from Neuroscience class) contain axons of low threshold mechanoreceptive afferents. A lesion placed as indicated in C selectively (midline dorsal column myelotomy) eliminates, or at least reduces, visceral pain (e.g., from visceral cancer), but would have no effect upon somatic pain.

Which pain is commonly experienced as more unpleasant, cutaneous or visceral?

Visceral. The localization of pain matters.

What is resposiple for some perceptual aspects of temperature and pain, autonomic / visceral responses to pain, emotional respoonses to pain?

Vmpo --> posterior insula

Which recieves both non-nociceptive and nociceptive, LT, NS, or WDR?

WDR has both. NS is nociceptive, LT is non-nociceptive.

What is the second stage of the Affective component of pain?

When Pain is of Longer Duration and is associated with complex emotions such as depression, anger, frustration. Or, Chronic Pain.

What is the the role of Injured Nociceptors when discussing hyperalgesia?

When a nerve is severed, a nociceptor is also severed. The damaged nerve generates neuroma and it tries to re-innervate the target tissue. The A-delta and C fibers create an ectopic discharge (spontaneous activity); this can contribute to development of hyperalgesia; for example, if you inject the local nerve with anesthetic, it significantly helps with the pain.

How a noxious thermal stimulus is transduced into electrical events and by a specific receptor called what?

When a noxious heat is applied to the skin, the noxious heat some how changes the gating properties of this TRP channel to undergo conformational changes to open the channel and is permeable; since this is a non-selective cationic channel, when they open, positively charged ions like sodium or calcium will flow in thru the channel. This influx of positively charged ions will bring depolarization of nerve terminal to cause a generated potential. If its sufficient in magnitude, when it reaches the threshold it will generate an AP. The receptor is a TRPV1

And when another inflammatory mediator, like PGE2 in injected, what happens?

When another inflammatory mediator, like PGE2, is injected in, it does not generate ongoing spontaneous activity or increase background discharge.

Why does a cracked tooth hurt only sometimes? And what happens if you don't treat it?

When hit a certain way, the crack is opened and fluids enter the tubules and stimulate the nerve endings. If untreated, tooth could end in total fracture.

What are a few examples of these chemical mediators and where do they come from?

When mast cells are degranulated, histamine is released; substance p can be released directly from nerve terminals; CGRP neuropeptide is directly released from nerve terminals; 5ht4 from platelets; bradykinin from blood plasma; ATP from damages cells.

What is propagation?

When the action potentials are conducted along the axon. Sensitization can involve changes in conductance of nerve impulses- e.g. injury or inflammation can change passive properties, such as membrane resistance or internal resistance of a nociceptor.

What is release?

When the action potentials invading central or peripheral terminals cause the vesicular release of transmitters. Sensitization can result from excessive release of neuromodulators or neurotransmitters- e.g. injury or inflammation can enhance the peripheral release of sensitizing agents.

What is initiation?

When the generator potential is converted into an action potential. Sensitization can involve the spike initiation zone- e.g. injury or inflammation can alter the expression and functional properties of voltage gated Na+ channels They can alter the function of the channels in such a way that it becomes easier to initiate an action potential.

What does PGE2 do to a neuronal response to stimuli in conjunction with bradykinin?

When you reintroduce bradykinin again after introduction of PGE2, bradykinin has an even GREATER response. PGE2 didn't activate the cell, but it DID enhance the subsequent bradykinin response. This is nociceptor sensitization WITHOUT nociceptor activation. PGE2 didn't activate cell, but it did enhance the bradykinin response.

How do we overcome the issue that human pain recordings cannot be compared to monkey recordings?

With Human microneurographic recordings, where the responses of CMHs recorded in awake humans and ratings of pain over the temperature range of 39-51C are highly correlated. Percutaneous electrodes are inserted directly into the neurofascicles of human subjects so you can record from human fascicles following application of noxious stimuli the receptive field of the nerve and obtain psychophysical data from the same human subjects. This provides strong evidence that c-fiber activity contribute to perception of pain in this temperature range.

Who seeks care for pain more, women or men?

Women.

Is wind-up NMDA receptor dependent?

Yes

Are the two different schemes equivalent?

Yes, these two different schemes are roughly equivalent in that a-alpha fibers are similar to group I in axon diameter; a-beta: group II; a-delta: group III, c-fibers;group IV

Does the endoneurium terminate before the end of axon and before the axon projects out into the peripheral tissue and terminate as free-nerve ending?

Yes. Both myelination and endoneurium terminate before this in a-delta fibers, and just the endoneurium in c-fibers that lack myelination.

Are emotions and facial contagious? If so, how do we know this?

Yes. In facial electromyographical (EMG) studies, viewing smiling and frowning faces implicitly activate corresponding ''zygomaticus major muscle'' and ''corrugator muscle,'' respectively, in the viewer. Also, in fMRI studies, similar parts of the brain are activated when studying emotions.

Are periapical lesions painless?

Yes. Patients don't all go through same conditions when it comes to pain. This same radiograph could be of a patient with severe swelling and life threatening infection.

Does pain influence mood?

Yes. There is a pain related state of mood, when ever a person is in pain they are in a certain mood and they have certain mannerisms and also pain reduces range of motion. Results in some form of disability.

Have we scientifically determined which fibers carry first and second pain?

Yes. We can demonstrate that a-delta fibers are responsible for first pain under ischemic conditions where a-delta fibers are blocked. When we stimulate nerves in a noxious range, you do not evoke first pain any longer while second pain or slow pain is still in tact (mediated by c-fibers). Conversely you can selectively eliminate c-fibers with local anesthetic by titrating a dose of local anesthetic to selectively block c-fiber input while leaving a-delta fiber input alone; if you stimulate the nerve you will evoke first pain while eliminating second pain. These experimental studies have confirmed that first pain is carried by a-delta and second pain is carried by c-fibers.

More on Central Sensitization

You have an acute stimulus ( Pinch of the cheek) that causes a series of AP's to come down to primary afferent that projects into the spinal cord. They synapes on dorsal horn neurons to produce a response. Central sensitization: an increase in excitability of dorsal horn neurons in addition to peripheral sensitization. Key to this is the understanding that synaptic processing in the spinal cord is not hard-wired, but can become modified, it exhibits plasticity ranging from broad increases in membrane potential to changes in protein phosphorylation and gene expression to loss of neurons and formation of new synapses. Central sensitization underlies secondary hyperalgesia: an increases perception of pain from noninjured tissue; and likely contributes to primary hyperalgesia.

The dorsal root reflex has been implicated in what conditions?

asthma, migraines, and rheumatoid arthritis.

Neurogenic inflammation is mediated by ?

axon-reflex or dorsal root reflex.

Both a-delta and c-fibers are surrounded by a layer of connective tissue called what?

endoneurium.

What are excitatory neurotransmitters for interneurons?

glutamine, substance P...

Is there more white or grey matter at L5 of the spinal cord compared to C5?

grey mater (This is because the there are less ascending fibers at the bottom)

TRPV1 channels are non-selective cationic channels that are activated by three things. What are those three thermal stimuli?

heat, capsaicin and protons

Neurogenic inflammation is an inflammatory condition produced by substances released directly from nerve terminals. Nociceptors, therefore, can serve regulatory and trophic functions like what?

microcirculation, metabolism, niociceptor excitability.

Hyperalgesia is a prominent symptom in clinical conditions such as?

postherpetic neuralgia, diabetic or HIV-associated neuropathy, and traumatic nerve injury.

Which area in the thoracic spinal cord houses the neurons of the parasympathetic system?

sacral parasympathetic nucleus

Each cell is wrapped around completely by a single layer of?

satellite or supportive cells.

When describing visceral/cutaneous nerves, what kind of terminology is used and what is it based on?

terminology like a delta, beta, gamma, alpha or c fibers are used; this is based on conduction velocities.

Sensitization can be observed in response to what kind of stimuli?

thermal, mechanical and/or chemical stimuli.

In the animal model of neuropathic pain, what does a ligated or cut spinal nerve result in?

this kind of experimental injury leads to mechanical and heat hyperalgesia in the affected body region.

The efferent function of nociceptors results in what?

vasodilatation(by CGRP) and plasma extravasation(by Substance p, released directly from nerve terminals) leading to neurogenic inflammation.

Peripheral neuropathic pain occurs when?

when the lesion or dysfunction affects the peripheral nervous system.