Neuroscience of Pain

nociceptors that only respond when under conditions of inflammation are called

'sleeping' or 'silent' nociceptors

Describe 3 Mechanisms in which chemical mediators have been shown to sensitize nociceptors in the setting of inflammatory conditions. What part of the signaling pathway does each affect

1. Direct actions on ionotropic receptors: - ATP --> P2X3 receptors and hypersensitizes: Transduction - Protons --> TRPV1 and hypersensitizes: Transduction 2. Gq protein-PKC pathway: - bradykinin --> Gq --> PKC --> lowers the activation threshold for temperature: Transduction 3. Gs protein-PKA pathway -prostanoids --> Gs --> PKA --> easier to initiate an action potential: Initiation

T/F Visceral information travels in the dorsal columns,with the spinothalamic tract (STT).

False ( Visceral information travels in the dorsal columns, separate from the STT, in the Ascending Visceral Pathway it is a ipsilateral pathway )

All nociceptors terminate in Meissner corpuscle Pacinian Corpuscle Ruffini's corpuscles Merkels disks Free nerve ending

Free nerve ending ( While nociceptors can be distinguished based on whether they have myelination or not of their axons all nociceptors terminate in fee nerve endings; meaning they do not have specialized receptors associated with their endings )

a lesion to left medulla would affect pain on the ______ side of the face and the ________ side of the body, and why.

the left side of the face (trigeminal is ipsilateral) the right side of the body (SST is contralateral) ( this is known as Wallenberg syndrome )

What is referred pain?

the perception of pain in one location (usually skin or muscle) when the origin of the pain is elsewhere (usually a visceral organ). This is likely due to viscerosomatic convergence in the dorsal horn

What are the efferent function of nociceptors (in general)

they release chemical mediators from their peripheral endings --> results in vasodilatation and plasma extravasation leading to neurogenic inflammation.

What is the major pathway that is involved in relaying somatic nociceptive and thermoreceptive information to brain from the face

trigemothalamic tract (TTT)

Dorsal Root Ganglia and Trigeminal Ganglia are _____________ neurons that project bifurcated axons to both peripherally and centrally

unipolar ( these neurons essentially have one cell body and one long process The long axon is bifurcated at the T-junction near the cell body giving rise to both central and peripheral processes )

Why can you not localize visceral afferent pain

visceral stimuli are more widespread in the spinal cord compared to cutaneous stimuli Therefore: The somatotopic organization is lost, contributing to the diffuse feeling and poor localization of a visceral stimulus.

Describe the Dorsal Root Reflex efferent function of nociceptors

works similarly to Axon Reflex If depolarization is large enough at the central terminals within the dorsal root, it can then travel backward, antidromically, to peripheral terminals causing the release of inflammatory mediators, which then results in neurogenic inflammation.

Describe the Axon Reflex efferent function of nociceptors

1. A noxious stimulus evokes an action potential in nociceptor fibers 2. Signal not only travels to the CNS but also spreads into nearby branches of the same nociceptor 3. This causes depolarizing of peripheral terminal -->antidromic propagation 4. The depolarization of the peripheral terminals causes their channels to open, causing an influx of Calcium ions 5. This causes the peripheral terminal to activate and release their chemical mediator into the surrounding tissues basically the activation of one axon can cause an efferent response to the surrounding nociceptors

describe the 4 steps in Primary Afferent Nociceptor Signaling

1. Transduction- a conversion of energy from the environment to a generator/graded potential (not all or nothing) 2. Initiation - generator potential is converted into an action potential (all or nothing signal) 3. Propagation - action potentials are conducted along the axon 4. Release - action potentials invading central or peripheral terminals cause the vesicular release of transmitters

How does a Mechanical nociceptors transduce various stimuli into electrical events

2 methods: Direct: strong mechanical pressure or deformation of the tissue can cause conformational changes in the protein and open the channel (this has not been directly proven) Indirect: stretch or tissue deformation evokes a release of chemical substances (E.g. ATP) from the local tissue or nerve terminals, which then excite nearby primary afferent nociceptors --> seen in the bladder with P2X receptors for ATP

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

Analgesia

What is the difference between Type I AMH and Type II AMH

AMH = A-delta mechano-heat nociceptors 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

Which receptors respond to acidic conditions

ASIC (Acid Sensing Ion Channel) and TRPV1 ( P2X receptor is for ATP molecule )

________ is pain due to a stimulus which does not normally provoke pain

Allodynia (think sunburn)

How does Chronic Hyperalgesia & Allodynia occur

Central Sensitization/secondary hyperalgesia can cause so much calcium to enter into the cell during a stimulation that the calcium can alter the gene expression and if it persists beyond the normal healing time of the injury as occurs with nerve injury --> leads to chronic pathophysiological pain

What is subliminal fringe?

Dendritic receptive field that does not normally get invoked

what is the function of the dorsal and ventral horns of the spinal cord

Dorsal --> afferent Ventral --> efferent (motor)

The cell bodies of nociceptors are located where ( Test Q slide )

Dorsal Root Ganglia (Spinal Root Ganglia) --> Body Trigeminal Ganglia (Gasserian ganglia) --> Craniofacial

What lamina make up the Dorsal and Ventral Horn

Dorsal horn = I-V Ventral horn = VIII, IX

What are the 3 layers of the connective tissue that surrounds the spinal cord

Dura matter (outer) -surround the larger blood vessels and venous sinuses Arachnoid (middle) - envelope for the cerebral spinal fluid that cushions the brain and spinal cord Pia Mater (inner) - contains the capillaries that supply nutrients to the brain

What cell in the spinal cord is a major player in hyperalgesia, allodynia and ongoing pain What is their role in pain

Glial/microglial cells increasing release of inflammatory cytokines which increase neuronal excitability causing hyperalgesia and allodynia.

what is the difference between white matter and gray matter

Gray is the cell bodies White is the axons

Greek letters are used to describe Myelination of ________ while Roman numerals are used to describe Myelination of ________

Greek letters --> Cutaneous/Visceral Nerves Roman numerals --> Muscle/Joint Nerves

_________ is an increased response to a stimulus which is normally painful

Hyperalgesia

What is the difference between Hyperalgesia and Sensitization

Hyperalgesia: subject/behavioral response -Decreased pain threshold -Increased pain to suprathreshold stimuli -Spontaneous pain Peripheral Sensitization: nociceptor response -Decreased threshold for response -Increased response to suprathreshold stimuli -Spontaneous activity hyperglycemia is a behavioral manifestation of Peripheral Sensitization

Windup definition

Increased response of dorsal horn neurons due to constant primary afferent input

In primary afferent stimulation, what is windup

Increased response of dorsal horn neurons due to constant primary afferent input constant C-fiber input causes a temporary release of the Mg2+ block of the NMDA receptor which further increases Ca2+ influx into the dorsal horn neuron increasing excitability

Explain how secondary hyperalgesia occurs

It is a Central sensitization stemming form the dorsal horn neuron intense tissue damage evokes a prolonged discharge in the original primary afferent, increasing excitability of the its DHn neuron if it excites it enough, the DHn will be able to activate adjacent DHn that are connected with a Subliminal fringe (a distal synapse but it does not produce enough activity normally to cause the neuron to fire) You can tell it is a DHn problem, because if you stimulated the secondary area in the periphery, it will not produce hyperalgesia

Low threshold (LT) neurons are most numerous in laminae Wide Dynamic Range (WDR) neurons are most numerous in the Nociceptive specific (NS) neurons are most numerous in

LT --> laminae III-V. WDR --> deeper laminae, IV-V. NS--> laminae I and II (superficial dorsal horn) and followed by laminae V-VI

Which spinal cord lamina is the motoneuron pool

Lamina IX

Which spinal cord lamina is involved in viscerosensory processing

Lamina X

A leftward shift in the pain intensity/stimulus intensity curve represents while a rightward shift represents:

Left: Hyperalgesia and Allodynia at the base of the curve Right Analgesia

neurons receive input from nonnociceptive afferents only Low threshold (LT) Wide Dynamic Range (WDR) Nociceptive specific (NS)

Low threshold (LT)

Myelinated Nociceptor are mostly made of __________ fibers Unmyelinated Nociceptor are mostly made of __________ fibers which is more common

Myelinated --> A-delta(Group III) fibers Unmyelinated --> C (Group IV) fibers Unmyelinated makes up ~70% of Nociceptor

What are the chemical nociceptors for Nerve Growth Factor (NGF) Bradykinin Serotonin

NGF --> TrkA Bradykinin --> BK2 Serotonin --> 5-HT3

What receptors is needed for windup

NMDA receptors

Someone had an implant placed in their lower jaw and now feels pain/ tingling

Neuroma in inferior alveolar nerve nerve is severed, the nociceptors are also severed, and the injured nociceptors develop what is called neuroma --> sprouting axons as an attempt for system to re-innervate the tissue

____________ is Pain initiated or caused by a primary lesion or dysfunction in the nervous system, which tends to cause __________

Neuropathic pain --> Hyperalgesia

neurons receive input from nociceptive afferents only Low threshold (LT) Wide Dynamic Range (WDR) Nociceptive specific (NS)

Nociceptive specific (NS)

What is the The role of inhibition in preventing chronic pathophysiological pain

Normally, inhibitory interneurons hyperpolarize the postsynaptic neuron by increasing Cl- influx through GABA A receptors However, inhibitory interneurons are susceptible to glutamate excitotoxicity and cell death (apoptosis) during prolonged afferent input. Loss of this inhibitory control (disinhibition) leads to an increase in neuronal hyperexcitability and hyperalgesia/allodynia Since there is neuronal death, these changes tend to be permanent --> Chronic pain

nociceptors are what type of receptors (think location)

Primary afferent ( So the term nociceptor used in my lectures refers to a primary afferent neuron comprised of a cell body, peripheral process that receives noxious signals central process that transmits this noxious information centrally )

a leftward shift in the stimulus response function that relates the magnitude of neural responses to stimulus intensity.

Sensitization ( it is different than Hyperalgesia because it is related to the neural response not the severity of pain felt Sensitization can cause Hyperalgesia can be observed in peripheral and central neurons can be observed in response to thermal, mechanical and/or chemical stimuli )

what is the difference between Slowly and Rapidly adapting nociceptors

Slowly adapting nociceptors exhibit sustained responses to a noxious stimulus. Rapidly adapting nociceptors respond only at the onset of stimulation.

When looking at cells in the ganglion, how could you potentially identify the nociceptors

Smaller cells are more likely to be nociceptors

What are the three Modalities of nociceptors

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

what receptor responds to a noxious cold stimulus

Thermal nociceptors TRPA1

Which receptor is responsive to high heat at 45 degrees C TRPV1 TRPV2

TRPV1 ( TRPV2 has a higher threshold response to heat (52 degrees Celsius), but not sensitive to capsaicin )

What is the difference between TRPV1 and TRPV2

TRPV1 is found in C and A-delta fibers and is activated by moderate heat (~45° C) and by capsaicin TRPV2 has a higher threshold response to heat (52°), not sensitive to capsaicin, and found mainly in A-delta fibers.

____________ is the psychophysical equivalent of windup; humans report increasing pain sensations to repetitive applications of noxious thermal or mechanical stimuli

Temporal summation ( temporal summation decreases as the interval between stimuli increases. If the interstimulus interval increases to 10 s, there is no temporal summation- each stimulus feels the same. windup is Increased response of dorsal horn neurons due to constant primary afferent input )

What accounts for the localization of cutaneous afferents?

Terminates in spinal cord in a way that creates somatotopic map

What are 2 of the main efferent chemical mediator released by nociceptors

substance P --> induces plasma extravasation calcitonin-gene related peptide (CGRP) --> a vasodilator

_________ is a chronic pain condition that affects the trigeminal nerve. It is a form of neuropathic pain. The typical or "classic" form of the disorder causes extreme, burning or shock-like facial pain that lasts anywhere from a few seconds to as long as few minutes per episode.

Trigeminal Neuralgia (TN)

T/F Intact Nociceptors fibers also contribute to neuropathic pain and hyperalgesia

True

T/F The distribution of the termination of muscle nociceptive afferents is in between cutaneous nociceptors and visceral afferents.

True

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

True ( out of all the unmyelinated axons: only half are sensory the other half are vasomotor of the sensory, only half of those are nociceptors So nociceptors make up about 1/4 of all unmyelinated axons )

Ventroposteriolateral (VPL) nucleus gets its input from Ventroposteriomedial (VPM) nucleus gets its input from

VPL --> spinothalamic tract (STT) VPM --> trigemothalamic tract (TTT)

Describe the The Role of Injured Nociceptors in abnormal activities in nociceptive fibers

When a nerve is severed, the nociceptors are also severed, and the injured nociceptors develop what is called neuroma --> sprouting axons as an attempt for system to re-innervate the tissue This neuroma produces abnormal spontaneous activity from A-delta and C- fibers, known as ectopic discharge ectopic discharge --> hyperalgesia chronic pain in peripheral nerve damage --> Ectopic release

How does the white and gray matter change going from cervical to sacral

White --> decreases Gray --> More in the cervical and the lumbar You need more gray matter in the cervical and lumbar spinal cord because there is more sensory processing (ex the arms/hands --> cervical spinal cord, feet --> lumbar) you have more white matter higher up to accommodate the ascending fibers going to the brain

neurons receive input from nociceptive and nonnociceptive afferents Low threshold (LT) Wide Dynamic Range (WDR) Nociceptive specific (NS)

Wide Dynamic Range (WDR)

Neurogenic inflammation a. Inflammatory products released by nociceptors b. Cytokine products released by microglia

a. Inflammatory products released by nociceptors

Which is true about windup a. It is a electrophysiological phenomenon b. Boys feel it more than girls c. It is not activity dependent

a. It is a psychophysical phenomenon ( as Windup, the electrophysiological response of a WDR neuron to constant C-fiber input: a progressive increase in the output of the dorsal horn neuron to a steady input from the primary afferents. Girls feel it more than boys )

Which is true of nociceptors? a. Respond to only noxious stimuli b. All unmyelinated neurons are nociceptive c. All of the above

a. Respond to only noxious stimuli ( While the majority of nociceptors have unmyelinated axons, not all unmyelinated axons belong to nociceptors )

The first location for processing of orofacial pain is a. Subnucleus Caudalis (Vc) b. Trigeminal ganglion c. Subnucleus interpolaris (Vi) d. Subnucleus oralis (Vo)

a. Subnucleus Caudalis (Vc) ( The Vc has functional and morphological similarities with the spinal cord DH, and has been implicated as the essential area for orofacial nociceptive processing. Nociceptive afferents project mainly to Vc Subnucleus Caudalis (Vc) projects to Subnucleus interpolaris (Vi) for further processing )

TRPV1 receptors deal with a. Transduction b.Initiation c.Propagation d.Release

a. Transduction ( Nociceptors terminate in free nerve endings, that is, there is no morphologically specialized receptor associated with nociceptor terminals. So free nerve endings in nociceptors must contain specialized transduction machineries to detect physical and chemical stimuli and convert them in to electrical signals. There are molecular transducers for noxious heat as well as noxious cold stimuli. Molecules that directly transduce noxious mechanical stimuli are NOT known yet. There are chemical transducers that respond to specific chemical mediators. )

Describe Viscerosomatic and Viscerovisceral Convergence

afferents that innervate different tissues but have their cell bodies in the same dorsal root ganglion can synapse onto the same dorsal horn neuron. This leads to convergence of somatic and visceral input (aka a single dorsal horn neuron can respond to multiple modalities of input) Referred pain results from convergence of visceral and somatic input; think pain in the shoulder during a heart attack.

Which of the following are characteristic sites of secondary hyperalgesia? a. Decreased pain at the original site of injury b. Increased sensitivity to painful stimuli outside of the area of injury c. Pain produced by bright visual stimuli d. Referred pain to distant site e. No response to low threshold mechanical stimuli

b. Increased sensitivity to painful stimuli outside of the area of injury ( d. Referred pain to distant site --> VISCERAL PAIN or referred pain )

Fiber tracts passing from the thalamus to the cerebral cortex are found in which of the following (National Board Question)? a. Corpus callosum b. Internal capsule c. Medial lemniscus d. Lateral lemniscus e. Anterior commissure

b. Internal capsule ( need to look up )

What are 3 ways to classify nociceptive afferents? a. Myelination, internal resistance and membrane resistance b. Myelination, modalities of acting stimuli, response properties c. Afferents mediating first, second and third pain d. Transmitter content, target of innervation and Ca2+ binding proteinse. e. All of the above

b. Myelination, modalities of acting stimuli, response properties ( Response Properties → A-delta nociceptors can be classified into two types based on their response=s to sustained stimuli. Type 1 AMH (Ad mechano-heat nociceptors) - are slowly adapting, and they are "tuned" to detect the continued presence of noxious stimuli. Type 2 AMH - are rapidly adapting, and they are "tuned" to detect changes in stimuli --- @ onset of stimulus )

Persistent nerve injury: a. Produces peripheral sensitization b. Produces central sensitization c. Involves WDR neurons primarily in laminae 4 d. Leads to activation of peripheral nociceptors e. All of the above

b. Produces central sensitization

What is a functional consequence of the fact that some nociceptors are myelinated axons and other have unmyelinated axons? a. It provides a nice way to classify nociceptors b. The phenomena of "first" pain and "second" pain, whereby a single stimulus at a distal site (i.e.: your toe) is able to evoke two distinct pain sensations that are temporally separated c. C-fibers have unmyelinated axons while A-delta fibers have thinly myelinated axons d. One is always rapidly adapting while the other may be rapidly or slowly adapting e. There is no functional consequence of this fact

b. The phenomena of "first" pain and "second" pain, whereby a single stimulus at a distal site (i.e.: your toe) is able to evoke two distinct pain sensations that are temporally separated

What enables high threshold thermoreceptors to respond to noxious thermal stimuli and chemoreceptors to respond to noxious chemical stimuli? a. It is a mysterious processg b. Changes in passive properties such as input resistance and capacitance c. Distinct proteins that undergo conformational changes (changes in shape) in response to specific stimuli (such as changes in temperature or the presence of a chemical) such that the stimulus ultimately leads to membrane depolarization d. Thermoreceptors may respond to either increases in temperature or decreases in temperature e. These receptors to not respond to such stimuli, nociceptors do

c. Distinct proteins that undergo conformational changes (changes in shape) in response to specific stimuli (such as changes in temperature or the presence of a chemical) such that the stimulus ultimately leads to membrane depolarization

In the theoretical pain case, what term best describes the increase pain Mr. P experienced when he jabbed his swollen foot with a pin? a. Allodynia b. Analgesia c. Hyperalgesia d. Guarding e. Imaginary

c. Hyperalgesia

The phenomenon of Central Sensitization: a. Is characteristic of peripheral nociceptors after persistent injury b. Is due to the influx of sodium into dorsal horn low threshold neurons c. Involves excitatory amino acid and neuropeptide receptors d. Occurs in the medullary dorsal horn after touching a hot stove e. Involves the release of serotonin and enkephalin from descending neurons

c. Involves excitatory amino acid and neuropeptide receptors

Nociceptive neurons in the medullary dorsal horn: a. Respond only to noxious thermal and mechanical stimuli b. Include wide dynamic range neurons and nociceptive specific neurons projecting from lamina II to the thalamus c. Respond to all of the following neurochemicals: Glutamate, GABA, Substance P, CGRP, Somatostatin d. Exhibit peripheral sensitization e. Are present in laminae 3 and 4

c. Respond to all of the following neurochemicals: Glutamate, GABA, Substance P, CGRP, Somatostatin ( Nociceptive laminae are 1, 2, and 5 )

How does a chemical nociceptors transduce various stimuli into electrical events ( Test Q slide )

chemical binds directly to the receptor in one of 2 ways: Ionotropic receptors (ligand-gated channels): receptor is an integral part (central pore) of the ion channel that it regulates --> direct Metabotropic receptors: receptor is distinct from the ion channel it regulates. ligand binding activates second messenger (G-protein) cascades that alter channel gating --> Bradykinin, prostaglandin

Which of the following contain the cell bodies of primary afferent nociceptive neurons: a. Nucleus gracillis b. Descending nucleus of V c. Mesencephalic Nucleus of V d. Dorsal Root Ganglion e. All of the above

d. Dorsal Root Ganglion ( Primary afferents, including nociceptive afferents, have their cell bodies in the dorsal (posterior) root ganglion. )

Which of the following are amino acid receptors that respond to glutamate: a. GABA, NE, Gly b. NMDA, Substance P, Metabotropic glutamate c.Serotonin, AMPA CGRP d. Kainate, NMDA, AMPA e. Kainate, NMDA, GABA

d. Kainate, NMDA, AMPA ( Glutamate binds to AMPA/kainate receptors on dorsal horn neurons evoking a flexion reflex and the brief sensation of pain. Another glutamate receptor, the NMDA receptor, is blocked by Mg2+ and not functional at this time )

Can a single nociceptive afferent serve more than 1 function a. No- they exist solely to signal presence of noxious or potential tissue damaging stimuli b. Yes—it can signal first pain and second pain c. It depends on where it terminates in the spinal cord d. Yes-it can subserve both afferent and efferent functions e. None of the above

d. Yes-it can subserve both afferent and efferent functions ( efferent function causes neurogenic inflammation by axon reflex: Dorsal ganglion reflex. efferent → release chemical mediators from their peripheral endings )

Central sensitization is different from peripheral sensitization because: a. decreased threshold of nociceptors b. increased suprathreshold response of nociceptors c. spontaneous activation of nociceptors d. expansion of the receptor field

d. expansion of the receptor field --> secondary hyperalgesia ( The result of peripheral sensitization is primary hyperalgesia: a greater perception of pain from injured tissue. Central sensitization results in secondary hyperalgesia (among other things): an increased perception of pain from noninjured tissue. )

Define dermatome, myotome, viscerotome.

dermatome: is an area of skin that is mainly supplied by afferent nerve fibers from a single dorsal root of spinal nerve myotome: group of muscles that a single spinal nerve innervates viscerotome: The part of an abdominal organ that is supplied with afferent nerves from a single posterior root.

Central sensitization results from an increase in excitability of

dorsal horn neurons

Tissue injury that persists: a. Leads to activation of excitatory amino acids b. Removal of the magnesium block from dorsal horn nociceptive neurons c. The release of calcium from intracellular stores in some dorsal horn neurons d. Enlargement of nociceptive fields of dorsal horn neurons e. All of the above

e. All of the above

What stimulus modalities are most nociceptors responsive to? a. Light touch b. Noxious mechanical c. Noxious thermal d. Noxious chemical e. Noxious mechanical, thermal and chemical

e. Noxious mechanical, thermal and chemical

what structure covers the fibers of both A delta and C nociceptors fibers

endoneurium ( remember that C fibers are unmyelinated also note that all nociceptor fibers are free nerve endings, so there is no endoneurium covering the sensory terminal )

Main molecule for NMDA receptors

glutamate (needed for Windup in primary afferent stimulation)

What is secondary hyperalgesia

hyperalgesia occurring in a region of undamaged tissue, due to an expansion of the receptive field of the DHn

Sensitization of neurons can occur where

in peripheral and central neurons ( can be thermal, mechanical and/or chemical stimuli increase in response of the neurons, it is different than Hyperalgesia because it is related to the neural response not the severity of pain felt Sensitization can cause Hyperalgesia )

Explain the mechanism behind central sensitization

injury induces peripheral sensitization -->increases afferent input to the spinal cord This afferent signal leads to a long lasting depolarization of the postsynaptic membrane, similar to windup, but with the addition of metabotropic and ionotropic receptors leading to kinase (e.g., PKC, PKA, Src, ERK) activation. These receptor become more sensitized due to all the additional excitatory amino acids that are released into the spinal chord. the excitatory amino acids now cause stimuli that would normally not trigger an action potential to trigger --> This causes an increase in the receptive field of the dorsal horn neuron neuron (input to the subliminal fringe now becomes suprathreshold) this causes secondary hyperalgesia,

What lamina are involved in processing nociceptive information

nociceptive --> the superficial dorsal horn (laminae I, II) and lamina V C --> lamina 2 A-delta --> 1, 2 and 5 The superficial dorsal horn and deep dorsal horn laminae are most important for nociceptive processing. ( Laminae III and IV processes innocuous stimuli only A-beta --> III to VI )

a lesion in the lateral medulla would disrupt the nociceptive/thermoreceptive afferent fibers mechanoreceptive afferent fibers All of the above

nociceptive/thermoreceptive afferent fibers ( this is referring to trigeminal input nociceptive/thermoreceptive afferent fibers from the trigeminal travel in the middle medulla while trigeminal mechanoreceptive afferent fibers travel in the caudal medulla )

What receptors are associated with tissue damaging stimuli

nociceptors

the majority of nociceptors are Thermal Mechanical Chemical polymodal

polymodal ( The vast majority (~70%) of them are responsive to two or more modalities and many are responsive to all three these are called polymodal nocicepors )

How does a Thermal nociceptors transduce various stimuli into electrical events

receptors belong to a larger family of transient receptor potential (TRP) channels (most studied is TRPV1) TRPV1 channels are non-selective cationic channels that are activated by heat, capsaicin and protons. This means that when they are acted on by heat (>45C), capsaicin or protons, the TRPV1 channel will open and allow Na+ or Ca2+ into the cell which will trigger a nerve impulse

In a pain stimuli: The first sensation of sharp, shooting pain is carried by _______ fibers While the diffused and longer lasting throbbing pain is carried by _______ fibers Which are more sensitive to local anesthetic

sharp, shooting pain (First pain) --> A-delta (myelinated) (Fast Adapting) longer lasting throbbing pain (second pain) --> C fibers (unmyelinated) (Slow adapting) A-delta are more sensitive to local anesthetic ( you can selectively block the C-fiber input while leaving the input from A-delta fibers intact )

Central sensitization is activity dependent increase in synaptic efficiency in the

spinal cord

What is the major pathway that is involved in relaying somatic nociceptive and thermoreceptive information to brain from the body

spinothalamic tract (STT) ( note: is a crossed pathway, such that information from the left side of the body travels in the right tract, and vice versa. )