peripheral mechanisms of pain Flashcards

1
Q

sensation of pain is

A

the localization and intensity of the stimuli

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2
Q

the affective component of pain is

A

the emotional response to pain

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3
Q

acute pain is

A

short term and has an identifiable source (pricking a finger)

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4
Q

chronic pain is

A

long term and has a frequently non-identified source

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5
Q

normal pain is mediated by what type of fibers

A

a-delta and c-fiber

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6
Q

are a-delta fibers myelinated

A

yes, lightly

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7
Q

conduction velocity of a-delta vs c-fibers

A

a-delta fastest

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8
Q

size difference b/w a-delta and c-fibers

A

a-delta is larger

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9
Q

are c-fibers myelinated

A

nope

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10
Q

neuropeptide content of a-delta vs. c-fibers

A

a-delta has limited neuropeptide content whereas many c-fibers have neuropeptides. there are multiple types of c-fibers (peptidergic vs nonpeptidergic)

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11
Q

what type of channels do the a-delta fibers use

A

TTX sensitive, Na channels

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12
Q

what type of channels do the c-fibers use

A

TTX sensitive and TTX-resistant fibers

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13
Q

what types of pain/nociceptive specifity do a-delta fibers have

A

specific to MECHANICAL STIMULI (limited responses to heat and chemical stimuli)

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14
Q

what types of pain/nociceptive specificity does a c-fiber have

A

specific to mechanical, chemical, thermal. some are even polymodal (respond to several of these!).

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15
Q

pain sensed by a-delta vs. c-fibers

A

a-delta is “1st pain”: fast, sharp, well localized

c-fiber is “2nd pain”: slow, dull, burning pain that is poorly localized

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16
Q

pain transduction uses what types of receptors/channels

A

ENaCs (may play a role in mechanical nociception) and TRP receptors

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17
Q

TRP receptors role in pain transduction

A

transduce chemical/thermal nociception (maybe mechanical too) and non-noxious thermal transduction and mediate chemesthesis (chemical sensation like the spiciness of food)

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18
Q

TRP receptors play what role in tooth pain

A

they are located on odontoblasts

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19
Q

Chemesthesis is the detected by what type of fiber

A

c-fibers..and maybe a-delta

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20
Q

what is the vanilloid receptor

A

a subclass of TRP receptor called TRPV1

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21
Q

vanilloid receptor responds to what stimuli

A
  1. capsaicin (in chili peppers)
  2. heat
  3. protons
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22
Q

stimulation of the TRPV1 receptor results in what

A

influx of cations into the nerve fiber (Na and Ca)…which leads to the detection of the stimuli

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23
Q

what branches of the trigeminal nerve play a prominent role in chemesthesis (4)

A
  1. ethmoid (within the nose)
  2. poterior palatine (oral)
  3. nasopalatine (oral)
  4. lingual (oral)
    here, chemical stimuli have good access to the mucosal tissue and can easily stimulate TRP receptors here
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24
Q

the ethmoid nerve is sensitive to what

A

smelling salts/ammonia (it is located in the nose)….not through olfactory nerves!

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25
Q

TRP receptors are ____

A

chemosensitive….different classes of TRP receptors detect different chemicals and have different pain thresholds

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26
Q

chemesthesis has ___ threshold sensitivity

A

high threshold (compared to taste and olfaction)

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27
Q

can dental compounds activate chemesthesis

A

yes

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28
Q

can chemesthesis be treatment for certain pains

A

yes. drugs that contain capsaicin compounds can be used to treat pain…via desensitization

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29
Q

desensitization

A

intense of repeated stimuli on primary afferent nociceptors can make a nerve less responsive to those stimuli via: inactivation of voltage gated ion channels and depletion of neuropeptides

30
Q

tooth pain in the dentinal tubules is mediated by what fibers

A

a-delta…fibers extend into tubules

31
Q

what molecule is responsible for pain in dentin tubules

A

calcitonin gene related peptide CGRP

32
Q

what type of sensitivity is detected in the dentinal tubules

A

mechanical and thermal and chemical stimuli….SHARP pain

33
Q

tooth pain in the pulp chamber is mediated by what fibers

A

c-fibers

34
Q

what molecule is responsible for pain in the pulp chamber

A

substance p

35
Q

what type of sensitivity is detected in the pulp chamber

A

thermal and chemosensitivity to inflammatory mediators ….DULL THROBBING pain

36
Q

neuron theory of sharp pain in dentin tubule

A

a-delta fiber that contains TRP receptors on it extends up into the dentin tubule and is directly acted upon/stimulated by stimuli

37
Q

hydrodynamic theory of sharp pain in dentin tubule

A

stimuli cause/influence fluid movement within the dentin tubule which stimulates the a-delta fiber that is also within the dentin tubule

38
Q

odontoblast theory of sharp pain in dentin tubule

A

the odontoblast process extends all the way to the DEJ and acts as a sensory cell (contains TRP receptors on it) and then kinda “synapse” on an a-delta fiber outside of the dentin tubule

39
Q

what does the smear layer have to do with pain transduction

A

high pressure on a dentinal tubule will not cause pain unless the smear layer is removed

40
Q

what is a possible mechanism for how the odontoblast might activate an a-delta fiber (in the odontoblastic theory)

A
  1. depolarization by various TRP receptors on the odontoblast
  2. a.p is initiated (because the odontoblasts have voltage gated Na channels that allow this to occur!)
  3. ATP is released via membrane channels
  4. ATP activates the a-delta fiber via P2X3 receptors
41
Q

what is hyperalgesia

A

greater responsiveness to stimuli (causing pain)….includes allodynia (response to non-painful stimuli produces pain) and response to painful stimuli is greater than normal. pain is SPONTANEOUS and PROLONGED

42
Q

C-fiber response to thermal or mechanical injury

A

injury occurs and then c-fiber releases neuropeptides…Substance p or CGRP….this causes secondary event to occur

43
Q

substance p released from a c-fiber causes…

A

stimulation of mast cells…then mast cells can release histamine…which in turn can further activate c-fibers to increase the activity of the c-fiber to the CNS

44
Q

CGRP released from a c-fiber causes…

A

vasodilation and swelling in that area…this acts as a mechanical stimulus to activate the c-fiber more and increase its activity

45
Q

injury that causes bleeding causes what to happen

A

(same as mechanical/thermal injury events…andddd) clot formation to occur releasing bradykinin and platelet products/ 5HT aka serotonin to be present

46
Q

bleeding injuries, bradykinin causes

A

the c-fiber to be stimulated more

47
Q

5HT/serotonin released from a bleeding injury causes

A

stimulation of the c-fiber

48
Q

damage that causes infection/immune response causes what to occur

A

prostaglandins and cytokines to be released which make the c-fiber more sensitive to other chemicals (sensitization). protons are released here as well and stimulate the vanilloid receptor (TRPV1) which increases the sensitivity as well

49
Q

what releases nerve growth factor

A

mast cells in response to inflammation

50
Q

what is the role of nerve growth factor

A

peripheral sensitization (making the c-fiber more sensitive to other chemicals). NGF induces local receptor trafficking/increases their gene expression (makes more receptors on the c-fiber to make it more sensitive)

51
Q

in what direction is NGF transported

A

NGF is released by mast cells and transported RETROGRADE to the cell body to promote gene expression of receptors there

52
Q

what 3 things lead to sensitization of the V1 receptor during inflammation

A
  1. presence of inflammatory mediators
  2. Ca activated phosphorylation of V1 receptor
  3. increase in the receptor number
53
Q

how do prostaglandins sensitize a c-fiber

A

block SK (K+) channels in c-fibers. NORMALLY, these channels work by prolonging the refractory period (by causing hyperpolarization) to which c-fibers cannot respond to another stimulus. Prostaglandins block these channels and bring the c-fiber back to resting membrane potential faster so that c-fibers can respond to stimuli faster than normal…thus, sensitizing the c-fiber (making it more sensitive)

54
Q

sensitization of the TRPV1 receptor lowers the ___ threshold

A

temperature

55
Q

sensitization by prostaglandins decreases the ____ threshold

A

mechanical

56
Q

causalgia

A

burning pain

57
Q

allodynia

A

light touch leading to pain

58
Q

sympathetic nerve dystrophy

A

temperature induced pain

59
Q

phantom sensations

A

sensation in denervated tissue

60
Q

neuroma

A

tangled web of regenerating fibers in an area of nerve transection/breakage….collateral nerve sprouting that is sometimes painful

61
Q

schwann cells role in regeneration

A
  • they produce LAMNIN which acts as a substrate for regenerating axons
  • schwann cells secrete NGF also to regulate gene expression to promote sprouting of axons
62
Q

how is NGF transported from the schwann cell to the nerve

A

retrograde to the ganglion cell body

63
Q

what does NGF regulate the gene expression of (in the nerve)

A
  • structural components
  • n.t production
  • ion channels
  • receptors
64
Q

in nerve injury, what would the sympathetic response be

A

sympathetic fibers sprout and release noradrenaline to interact with the c-fiber

65
Q

what are the effects of noradrenaline (from sympathetic fibers) on a damaged c-fiber

A
  1. increases the Na channels on the c-fiber that are both TTX sensitive and resistant (which lowers the threshold to which the c-fiber is stimulated)
  2. creates new noradrenergic receptors on the c-fibers (so now the c-fiber can be stimulated by the sympathetic release of noradrenaline)
  3. channel placement is irregular (in regards to Na channels) and so now a response in the c-fiber to stimuli can be at an atypical site (like the ganglion)
66
Q

how does c-fiber microneurography (method of recording nerve impulses) change in response to injury

A

start to have ectopic/abnormal discharge of a.p (after injury)

67
Q

what events occur during c-fiber ectopic discharge (brought on by injury)

A
  1. spontaneous activity
  2. prolonged responses to known stimulus
  3. initiation of response from atypical site (brought on by sympathetics)
  4. injury induced increase in Na channels on the c-fiber (brought on by sympathetics)
68
Q

what is ephaptic transmission

A

abnormal signals/communication from the CNS. a-beta fiber communicates with a c-fiber…this is abnormal. since a-beta normally detects touch, a non-noxious touch will now cause communication/stimulation of a c-fiber (through the a-beta fiber) and now cause pain.

69
Q

what is ephaptic transmission the mechanism for

A

it is the mechanism for ALLOYDYNIA and REFERRED PAIN

70
Q

what are the 3 general responses to nerve injury that cause pain

A
  1. sprouting/increased fiber density (i think this probably includes the neuromas that can occur)
  2. ectopic discharge/activity
  3. ephaptic transmission