Notes (flash cards) from Ch1 Textbk of Pain 8.28.12 Flashcards by Shaness Grenald

Peripheral mechanisms of cutaneous nociception

what are nociceptors?

specialilzed class of primary afferents that respond to intense, noxious stimuli

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Peripheral mechanisms of nociception

what are nociceptors?

specialized class of primary afferents that respond to intense, noxious stimuli

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Peripheral mechanisms of cutaneous nociception

what do unmyelinated nociceptors do?

signal BURNING pain from intense heat applied to glabrous skin of hand as well as pain from sustained PRESSURE

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Peripheral mechanisms of nociception

what do unmyelinated nociceptors do?

signal BURNING pain from intense heat applied to glabrous skin of hand as well as pain from sustained PRESSURE

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Peripheral mechanisms of cutaneous nociception

what do myelinated nociceptors do?

signal SHARP pain from heat stimuli applied to hairy skin & from sharp mechanical stimuli

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Peripheral mechanisms of nociception

what do myelinated nociceptors do?

signal SHARP pain from heat stimuli applied to hairy skin & from sharp mechanical stimuli

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Peripheral mechanisms of cutaneous nociception

which type of nociceptor signals pain from mechanical stimuli?

both unmyelinated and myelinated nociceptors

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Peripheral mechanisms of nociception

which type of nociceptor signals pain from mechanical stimuli?

both unmyelinated and myelinated nociceptors

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Peripheral mechanisms of cutaneous nociception

what is hyperalgesia?

enhanced pain in response to cutaneous injury

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Peripheral mechanisms of nociception

what is hyperalgesia?

enhanced pain in response to cutaneous injury

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Peripheral mechanisms of cutaneous nociception

where does primary hyperalgesia occur?

site of injury

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Peripheral mechanisms of nociception

where does primary hyperalgesia occur?

site of injury

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Peripheral mechanisms of cutaneous nociception

where does secondary hyperalgesia occur?

surrounding uninjured skin

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Peripheral mechanisms of nociception

where does secondary hyperalgesia occur?

surrounding uninjured skin

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Peripheral mechanisms of cutaneous nociception

what is sensitization?

enhanced responsiveness of nociceptors

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Peripheral mechanisms of nociception

what is sensitization?

enhanced responsiveness of nociceptors

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Peripheral mechanisms of cutaneous nociception

what does sensitization account for?

primary hyperalgesia

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Peripheral mechanisms of nociception

what does sensitization account for?

primary hyperalgesia

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Peripheral mechanisms of cutaneous nociception

sensitization is due to what?

local release of inflammatory mediators

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Peripheral mechanisms of nociception

sensitization is due to what?

local release of inflammatory mediators

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Peripheral mechanisms of cutaneous nociception

secondary hyperalgesia is due to what?

sensitization of neurons in the CNS

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Peripheral mechanisms of nociception

secondary hyperalgesia is due to what?

sensitization of neurons in the CNS

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Peripheral mechanisms of cutaneous nociception

when nerves are severed, what do injured nociceptors develop?

spontaneous activity and ectoopic (abnormal) mechanical, thermal & chemical sensitivity

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Peripheral mechanisms of nociception

when nerves are severed, what do injured nociceptors develop?

spontaneous activity and ectopic (abnormal) mechanical, thermal & chemical sensitivity

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# Peripheral mechanisms of cutaneous nociception when nerves are severed, are the properties of uninjured nociceptors changed?

yes.

# Peripheral mechanisms of nociception when nerves are severed, are the properties of uninjured nociceptors changed?

yes.

# Peripheral mechanisms of cutaneous nociception both injured and uninjured nociceptors develop responsiveness to what agents, which may account for the involvement of the sympathetic nervous system in certain forms of neuropathic pain?

adrenergic agents

# Peripheral mechanisms of nociception both injured and uninjured nociceptors develop responsiveness to what agents, which may account for the involvement of the sympathetic nervous system in certain forms of neuropathic pain?

adrenergic agents

# Peripheral mechanisms of nociception name a vital function of the nervous system in regards to the sensation of pain.

to provide info about the occurrence or threat of injury

# Peripheral mechanisms of nociception how can one study cutaneous sensibility?

record from single nerve fibers in a receptive field

# Peripheral mechanisms of nociception warm fibers that signal the quality and intensity of warmth sensation are predominantly what type of fibers?

unmyelinated

# Peripheral mechanisms of nociception what type of fibers respond selectively to gentle cooling stimuli and encode the sense of cooling?

subpopulation of thinly myelinated A_ fibers

# Peripheral mechanisms of nociception what type of fibers signal the sense of touch (deformation of skin)?

mechanoreceptive afferent fibers

# Peripheral mechanisms of nociception what encodes for touch features such as texture and shape?

low-threshold mechanoreceptors

# Peripheral mechanisms of nociception what do nociceptors respond to?

the multiple energy forms that produce injury i.e. thermal, mechanical, & chemical stimuli

# Peripheral mechanisms of nociception what are the 4 criteria used to subclassify nociceptors?

1. unmyelinated, c-fiber afferents vs. myelinated, a-fiber afferents; 2. modalities of stimulation that evoke a response; 3. response characteristics; 4. distinctive chemical markers i.e. receptors expressed on membrane

# Peripheral mechanisms of nociception what are polymodal nociceptors?

nociceptors that respond to multiple stimulus modalities i.e. c-fiber mechano-heat-sensitive (CMH) or a-fiber mechano-heat- sensitive (AMH)

# Peripheral mechanisms of nociception how do you find a nociceptor for electrophysiological study?

squeeze (mechanical) stimuli to skin to identify receptive field (mechanically sensitive afferents (MSA))

# Peripheral mechanisms of nociception what are silent nociceptors?

mechanically insensitive afferents (MIA) with high mechanical thresholds (or are unresponsive to mechanical stimuli)

# Peripheral mechanisms of nociception about how many nociceptors are MIA?

about 50% of A_ fibers and 30% of c-fibers

# Peripheral mechanisms of nociception c-fiber mechano-heat-sensitive (CMH) nociceptors evoke what kind of pain sensation?

BURNING

# Peripheral mechanisms of nociception can CMHs respond to chemical stimuli?

yes, but not as well as a-fiber nociceptors

# Peripheral mechanisms of nociception T/FÉ. CMH response to heat stimuli increases monotonically with stimulus intensity.

TRUE

# Peripheral mechanisms of nociception like CMH, activation of what receptor with a heat stimulus increases with increasing temperature?

vanilloid receptor 1 (TRPV1)

# Peripheral mechanisms of nociception what does TRPV1 receptors respond to?

noxious heat, capsaicin, and protons

# Peripheral mechanisms of nociception disparity in the surface temperature compared with the temperature at the level of the CMH receptor varies directly with_____ and indirectly with _____.

depth; time

# Peripheral mechanisms of nociception c-fiber nociceptors exhibit what 2 things in response to repeated heat stimulation?

fatigue and sensitization

# Peripheral mechanisms of nociception some c-fiber MIAs are vigorously excited when exposed to what?

histamine or capsaicin

# Peripheral mechanisms of nociception c-fiber MIAs are thought to act as what type of sensors?

chemosensors

# Peripheral mechanisms of nociception c-fiber MIAs can account for what type of pain?

pain from tonic PRESSURE stimuli or the neurogenic flare response

# Peripheral mechanisms of nociception which fiber mediates the sensation of pleasant touch (affiliative behavior)?

low-threshold c-fiber mechanoreceptors

# Peripheral mechanisms of nociception what happens to the conduction latency of unmyelinated c-fiber afferents when they are activated repetitively by electrical stimuli?

conduction latency increases gradually (velocity slows)

# Peripheral mechanisms of nociception what kind of pain does a-fiber nociceptors evoke?

pricking, sharpness, aching

# Peripheral mechanisms of nociception a-fiber nociceptors respond with (higher/lower) discharge frequencies when compared to c-fiber nociceptors?

higher

# Peripheral mechanisms of nociception what are type I a-fiber nociceptors?

responds to heat, mechanical, chemical stimuli (polymodal); high-threshold mechanoreceptors; heat sensitivity mediated by TRPV2 receptors; seen in glabrous & hairy skin; nearly all are MSAs

# Peripheral mechanisms of nociception what are type II a-fiber nociceptors?

most are MIAs; mean conduction velocity is lower than type I; responses mediated by TRPV1

# Peripheral mechanisms of nociception which type of a-fiber nociceptor is thought to play a role in the development of hyperalgesia?

type I

# Peripheral mechanisms of nociception which type of a-fiber nociceptor is thought to signal 1st pain sensation from heat and may also contribute to pain from application of capsaicin to the skin?

type II

# Peripheral mechanisms of nociception T/FÉ the conduction velocity of small myelinated A_ fibers is slower than that of unmyelinated c-fibers?

FALSE.

# Peripheral mechanisms of nociception what are nociceptor molecules?

molecules expressed on the cell surface (e.g. receptors and glycoconjugates), molec's stored and released from nociceptive afferents (e.g. peptides), and enzymes

# Peripheral mechanisms of nociception cell bodies of nociceptive somatic and visceral afferents are located where?

dorsal root ganglia

# Peripheral mechanisms of nociception small dorsal root ganglion cells can be subdivided into what two types of neurons?

peptidergic and non-peptidergic neurons

# Peripheral mechanisms of nociception what are peptidergic neurons?

neurons containing peptides such as substance P, calcitonin gene-related peptide (CGRP), & somatostatin

# Peripheral mechanisms of nociception what do non-peptidergic neurons contain?

fluoride-resistant acid phosphotase (FRAP); stain positive for plant lectin IB4

# Peripheral mechanisms of nociception peptidergic fibers mainly project where?

lamina I and lamina II outer

# Peripheral mechanisms of nociception IB4 binding afferents preferably project where?

lamina II inner

# Peripheral mechanisms of nociception most peptidergic neurons express what receptor?

tyrosine kinase receptor A (TrkA) -> dependent on nerve growth factor (NGF)

# Peripheral mechanisms of nociception most IB4-positive dorsal root ganglion cells express what receptor?

glial cell line-derived neurotropic factor (GFRalpha 1-4) & receptor tyrosine kinase Ret

# Peripheral mechanisms of nociception tetrodotoxin-sensitive sodium channels expressed on nociceptive afferents are important for what?

conduction of nociceptive signals

# Peripheral mechanisms of nociception tetrodotoxin-resistant sodium channels expressed on nociceptive afferents are important for what?

modulatory role on peripheral nociceptors & in the generation of ectopic activity

# Peripheral mechanisms of nociception what is coupling?

activation of one fiber from action potential activity in another; involves conventional CMHs; is near the receptor; is bidirectional; coupling btwn peripheral nerve fibers is one pathological change associated with nerve injury

# Peripheral mechanisms of nociception T/F...c-fibers function is necessary for thermal pain perception?

TRUE

# Peripheral mechanisms of nociception in patients with congenital insensitivity to pain, which fibers are absent?

c-fibers

# Peripheral mechanisms of nociception the absence of a first pain sensation from heat stimuli applied to the glabrous skin of the hand would likely correlate with the absence of which nociceptor?

type II a-fiber nociceptors

# Peripheral mechanisms of nociception __-fiber nociceptors recover faster from fatigue than ___-fiber nociceptors.

a; c

# Peripheral mechanisms of nociception ____nociceptors appear to be responsible for sharp pain reported in response to punctate (sharp) mechanical stimuli

a-fiber

# Peripheral mechanisms of nociception ____ MIAs signal the pain associated with tonic pressure

c-fiber

# Peripheral mechanisms of nociception cold fibers are predominantly what type of nociceptor?

# Peripheral mechanisms of nociception ___ nociceptors respond to cold stimuli below 0 C; ___ nociceptors play a role in signaling cold pain sensation. Both of which are mediated through ____ (non-selective cation channel).

a-fiber; c-fiber; TRPA1

# Peripheral mechanisms of nociception when capsaicin is injected into the receptive field of ____, the response is weak and of short duration. In contrast, ___ and ___ exhibit long-lasting vigorous response to capsaicin which is mediated by the ___ receptor which is expressed on nociceptive fibers.

c-fiber MSAs; a-fiber and c-fiber MIAs; TRPV1

# Peripheral mechanisms of nociception injection of histamine into the receptive field of ___ leads to a weak, short lasting response. In contrast, administration of histamine into the receptive field of a subpopulation of ___ produces a vigorous, long-lasting response that is mediated through the ____ receptor located on peripheral terminals.

c-fiber MSAs; c-fiber MIAs; H1

# Peripheral mechanisms of nociception hyperalgesia is defined as the (leftward; rightward) shift of the stimulus response function that relates magnitude of pain to stimulus intensity.

leftward

# Peripheral mechanisms of nociception when the injury and the test site coincide, the study has provided basis by which to consider the mechanism for (primary/secondary hyperalgesia), whereas when the test site and injury site diverge, the study has provided a basis by which to account for (primary/secondary hyperalgesia).

primary hyperalgesia; secondary hyperalgesia

# Peripheral mechanisms of nociception ___ is characterized by a decrease in threshold, an augmented response to suprathreshold stimuli, ongoing spontaneous activity, and a leftward shift of the stimulus-response function.

sensitization

# Peripheral mechanisms of nociception it is likely that, for thermal injuries of to the glabrous skin, ___ and not ___ code for the heat hyperalgesia.

AMHs; CMHs

# Peripheral mechanisms of nociception hyperalgesia to heat stimuli that occurs at the site of an injury is due to _____ of primary afferent nociceptors.

sensitization

# Peripheral mechanisms of nociception T/FÉ inflammation results in a reduction in mechanical threshold of AMHs and CMHs.

FALSE.

# Peripheral mechanisms of nociception name some chemicals that mediate or facilitate the inflammatory process.

bradykinin, prostaglandins, leukotrienes, serotonin, histamine, substance P, thromboxanes, platelet-activating factor, adenosine and ATP, protons, free radicals, cytokines (i.e. interleukins (IL), tumor necrosis factor (TNF), and neurotrophins (i.e. NGF))

# Peripheral mechanisms of nociception bradykinin-induced nociceptor sensitization may result from activation of what?

phospholipase C, protein kinase C, the production of arachidonic acids & the modulation of the TRPV1 channel

# Peripheral mechanisms of nociception in inflamed tissues, the sensitivity of c-fiber nociceptors to bradykinin is mediated through which receptors?

# Peripheral mechanisms of nociception protons selectively activate nociceptors and produce sensitization of nociceptors to _____ stimuli.

mechanical

# Peripheral mechanisms of nociception mast cells, on degranulation, release platelet-activating factor, which in turn leads to ____ release from platelets. This substance can potentiate the pain induced by bradykinin.

serotonin

# Peripheral mechanisms of nociception substance P released from nociceptor terminals can cause the release of ____ from mast cells.

histamine

# Peripheral mechanisms of nociception the prostaglandins, thromboxanes, and leukotrienes are a large family of arachidonic acid metabolites collectively known as what?

eicosanoids

# Peripheral mechanisms of nociception which prostaglandins are most likely to have a role in inflammatory pain and hyperalgesia?

PGI2, PGE1, PGE2, PGD2

# Peripheral mechanisms of nociception how do PGs work?

decrease the threshold for activation of voltage-sensitive tetrodotoxin resistant Na+ current specific for nociceptors, increase cAMP levels, and increase the excitability of the sensory neuron

# Peripheral mechanisms of nociception which leukotrienes (metabolites of the lipooxygenase pathway) play a role in hyperalgesia?

leukotriene D4 & B4

# Peripheral mechanisms of nociception adenosine enhances the response to formalin presumably via the ____ receptor.

# Peripheral mechanisms of nociception ATP-induced pain is dependent on _____-sensitive neurons.

capsaicin

# Peripheral mechanisms of nociception ATP presumably activates nociceptive neurons in normal skin via the ____ and the heterometric _____ receptor.

P2X3; P2X2-P2X3

# Peripheral mechanisms of nociception aggregation of platelets or lysis of cells can lead to release of what?

ATP

# Peripheral mechanisms of nociception during inflammation, which cytokines are released from macrophages and regulate the inflammatory response?

IL1_, TNF_, and IL6

# Peripheral mechanisms of nociception a number of excitatory amino acid and peptide receptors are present where?

post-synaptic sites in the dorsal horn

# Peripheral mechanisms of nociception excitatory amino acid glutamate can act through which 2 types of receptors?

ligand-gated ion ch (ionotropic glutamate receptors) or G protein coupled metabotropic (mGlu) receptors

# Peripheral mechanisms of nociception what are the endogenous sources of glutamate in the periphery?

plasma, macrophages, epithelial and dendritic cells in the epidermis and dermis, and Schwann cells

# Peripheral mechanisms of nociception what roles does NGF play in inflammation?

stimulates mast cells to release serotonin and histamine, sensitizes nociceptors, may alter the distribution of A_ fibers so that more have nociceptive properties

# Peripheral mechanisms of nociception T/FÉ inflammatory cells such as macrophages, monocytes and lymphocytes contain opioid peptides.

TRUE

# Peripheral mechanisms of nociception release of endogenous opioids and antinociception can be induced by ____ and _____ originating from the inflamed tissue.

IL1_ and corticotrophin-releasing hormone

# Peripheral mechanisms of nociception There is an up-regulation of ___ after inflammation which contributes to the sensitization of nociceptors to heat.

TRPV1

# Peripheral mechanisms of nociception following inflammation, axonal transport of ____ mRNA is induced, the proportion of _____ (same answer)- labeled unmyelinated axons in the periphery is increased by almost 100%, and the sensitivity of DRG neurons and primary afferent fibers to capsaicin increases.

TRPV1

# Peripheral mechanisms of nociception nicotinic and muscarinic receptors have (similar/opposite) effects on cutaneous nociceptors.

opposite

# Peripheral mechanisms of nociception behavioral and electrophysiological studies with somatostatin antagonists (i.e. octreotide) suggests that somatostatin receptors maintain a tonic (excitatory/inhibitory) control on cutaneous nociceptors

inhibitory

# Peripheral mechanisms of nociception (central/peripheral) sensitization can be the result of changes in the transducer molecule i.e. TRPV1 receptor, or in the voltage-gated ion channels (i.e. sodium channels), that result from phosphorylation of membrane-bound proteins.

peripheral

# Peripheral mechanisms of nociception inflammatory mediators such as PGE2, serotonin, & adenosine activate protein kinase ___, while NGF, bradykinin and adrenaline induce hyperalgesia, in part, by activating protein kinase ___ and an E isozyme of protein kinase ___

A; A; C

# Peripheral mechanisms of nociception release of ___ from injured cells is considered to play an important role in the induction of mechanical allodynia after a skin incision.

ATP

# Peripheral mechanisms of nociception nociceptors normally (do/do not) respond to sympathetic stimulation.

do not

# Peripheral mechanisms of nociception (primary/secondary) hyperalgesia is characterized by the presence of enhanced pain from heat and mechanical stimuli, whereas (primary/secondary) hyperalgesia is characterized by enhanced pain from only mechanical stimuli

primary; secondary

# Peripheral mechanisms of nociception spreading sensitization of nociceptors (does/does not) occur.

does not

# Peripheral mechanisms of nociception what is central sensitization?

augmentation of responsiveness of central pain-signaling neurons to input from low-threshold mechanoreceptors

# Peripheral mechanisms of nociception when the central nervous system is spared (by a proximal nerve block) the input of nociceptors at the time of the acute insult, hyperalgesia (does/does not) develop.

does not

# Peripheral mechanisms of nociception plasticity in the response of (first/second) order neurons in the dorsal horn appears to be a major factor to account for central sensitization.

second

# Peripheral mechanisms of nociception punctate hyperalgesia disappears when ___ fibers are blocked.

# Peripheral mechanisms of nociception what 2 efferent cutaneous phenomena have been considered to be dependent on the integrity of afferent nociceptive fibers and are part of neurogenic inflammation?

vasodilation (visible as a flare around injury site) and plasma extravasation

# Peripheral mechanisms of nociception ____ is thought to be due to a peripheral axon reflex.

flare

# Peripheral mechanisms of nociception what 2 key concepts are involved in the understanding of neuropathic pain?

1. inappropriate activity in nociceptive fibers (injured and uninjured), 2. central changes in sensory processing that arise from these abnormalities

# Peripheral mechanisms of nociception T/FÉ when a nerve is severed, the nociceptors are also severed.

TRUE

# Peripheral mechanisms of nociception activity in nociceptors induces an increase in sympathetic discharge that is associated with a rise in ____ that may be seen in circumstances of acute pain.

blood pressure

# Peripheral mechanisms of nociception animal work strongly suggests that sympathetically maintained pain arises from expression of _____ receptors on the terminals of nociceptors.

_-adrenergic

# Peripheral mechanisms of nociception release of ____ from the sympathetic terminals activates the nociceptors that express _1-adrenergic receptors. The spontaneous activity and excitation that results lead to _____.

noradrenaline; central sensitization

Notes (flash cards) from Ch1 Textbk of Pain 8.28.12

(129 cards)