peripheral mechanisms of pain Flashcards
sensation of pain is
the localization and intensity of the stimuli
the affective component of pain is
the emotional response to pain
acute pain is
short term and has an identifiable source (pricking a finger)
chronic pain is
long term and has a frequently non-identified source
normal pain is mediated by what type of fibers
a-delta and c-fiber
are a-delta fibers myelinated
yes, lightly
conduction velocity of a-delta vs c-fibers
a-delta fastest
size difference b/w a-delta and c-fibers
a-delta is larger
are c-fibers myelinated
nope
neuropeptide content of a-delta vs. c-fibers
a-delta has limited neuropeptide content whereas many c-fibers have neuropeptides. there are multiple types of c-fibers (peptidergic vs nonpeptidergic)
what type of channels do the a-delta fibers use
TTX sensitive, Na channels
what type of channels do the c-fibers use
TTX sensitive and TTX-resistant fibers
what types of pain/nociceptive specifity do a-delta fibers have
specific to MECHANICAL STIMULI (limited responses to heat and chemical stimuli)
what types of pain/nociceptive specificity does a c-fiber have
specific to mechanical, chemical, thermal. some are even polymodal (respond to several of these!).
pain sensed by a-delta vs. c-fibers
a-delta is “1st pain”: fast, sharp, well localized
c-fiber is “2nd pain”: slow, dull, burning pain that is poorly localized
pain transduction uses what types of receptors/channels
ENaCs (may play a role in mechanical nociception) and TRP receptors
TRP receptors role in pain transduction
transduce chemical/thermal nociception (maybe mechanical too) and non-noxious thermal transduction and mediate chemesthesis (chemical sensation like the spiciness of food)
TRP receptors play what role in tooth pain
they are located on odontoblasts
Chemesthesis is the detected by what type of fiber
c-fibers..and maybe a-delta
what is the vanilloid receptor
a subclass of TRP receptor called TRPV1
vanilloid receptor responds to what stimuli
- capsaicin (in chili peppers)
- heat
- protons
stimulation of the TRPV1 receptor results in what
influx of cations into the nerve fiber (Na and Ca)…which leads to the detection of the stimuli
what branches of the trigeminal nerve play a prominent role in chemesthesis (4)
- ethmoid (within the nose)
- poterior palatine (oral)
- nasopalatine (oral)
- lingual (oral)
here, chemical stimuli have good access to the mucosal tissue and can easily stimulate TRP receptors here
the ethmoid nerve is sensitive to what
smelling salts/ammonia (it is located in the nose)….not through olfactory nerves!
TRP receptors are ____
chemosensitive….different classes of TRP receptors detect different chemicals and have different pain thresholds
chemesthesis has ___ threshold sensitivity
high threshold (compared to taste and olfaction)
can dental compounds activate chemesthesis
yes
can chemesthesis be treatment for certain pains
yes. drugs that contain capsaicin compounds can be used to treat pain…via desensitization
desensitization
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
tooth pain in the dentinal tubules is mediated by what fibers
a-delta…fibers extend into tubules
what molecule is responsible for pain in dentin tubules
calcitonin gene related peptide CGRP
what type of sensitivity is detected in the dentinal tubules
mechanical and thermal and chemical stimuli….SHARP pain
tooth pain in the pulp chamber is mediated by what fibers
c-fibers
what molecule is responsible for pain in the pulp chamber
substance p
what type of sensitivity is detected in the pulp chamber
thermal and chemosensitivity to inflammatory mediators ….DULL THROBBING pain
neuron theory of sharp pain in dentin tubule
a-delta fiber that contains TRP receptors on it extends up into the dentin tubule and is directly acted upon/stimulated by stimuli
hydrodynamic theory of sharp pain in dentin tubule
stimuli cause/influence fluid movement within the dentin tubule which stimulates the a-delta fiber that is also within the dentin tubule
odontoblast theory of sharp pain in dentin tubule
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
what does the smear layer have to do with pain transduction
high pressure on a dentinal tubule will not cause pain unless the smear layer is removed
what is a possible mechanism for how the odontoblast might activate an a-delta fiber (in the odontoblastic theory)
- depolarization by various TRP receptors on the odontoblast
- a.p is initiated (because the odontoblasts have voltage gated Na channels that allow this to occur!)
- ATP is released via membrane channels
- ATP activates the a-delta fiber via P2X3 receptors
what is hyperalgesia
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
C-fiber response to thermal or mechanical injury
injury occurs and then c-fiber releases neuropeptides…Substance p or CGRP….this causes secondary event to occur
substance p released from a c-fiber causes…
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
CGRP released from a c-fiber causes…
vasodilation and swelling in that area…this acts as a mechanical stimulus to activate the c-fiber more and increase its activity
injury that causes bleeding causes what to happen
(same as mechanical/thermal injury events…andddd) clot formation to occur releasing bradykinin and platelet products/ 5HT aka serotonin to be present
bleeding injuries, bradykinin causes
the c-fiber to be stimulated more
5HT/serotonin released from a bleeding injury causes
stimulation of the c-fiber
damage that causes infection/immune response causes what to occur
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
what releases nerve growth factor
mast cells in response to inflammation
what is the role of nerve growth factor
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)
in what direction is NGF transported
NGF is released by mast cells and transported RETROGRADE to the cell body to promote gene expression of receptors there
what 3 things lead to sensitization of the V1 receptor during inflammation
- presence of inflammatory mediators
- Ca activated phosphorylation of V1 receptor
- increase in the receptor number
how do prostaglandins sensitize a c-fiber
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)
sensitization of the TRPV1 receptor lowers the ___ threshold
temperature
sensitization by prostaglandins decreases the ____ threshold
mechanical
causalgia
burning pain
allodynia
light touch leading to pain
sympathetic nerve dystrophy
temperature induced pain
phantom sensations
sensation in denervated tissue
neuroma
tangled web of regenerating fibers in an area of nerve transection/breakage….collateral nerve sprouting that is sometimes painful
schwann cells role in regeneration
- 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
how is NGF transported from the schwann cell to the nerve
retrograde to the ganglion cell body
what does NGF regulate the gene expression of (in the nerve)
- structural components
- n.t production
- ion channels
- receptors
in nerve injury, what would the sympathetic response be
sympathetic fibers sprout and release noradrenaline to interact with the c-fiber
what are the effects of noradrenaline (from sympathetic fibers) on a damaged c-fiber
- 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)
- creates new noradrenergic receptors on the c-fibers (so now the c-fiber can be stimulated by the sympathetic release of noradrenaline)
- 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)
how does c-fiber microneurography (method of recording nerve impulses) change in response to injury
start to have ectopic/abnormal discharge of a.p (after injury)
what events occur during c-fiber ectopic discharge (brought on by injury)
- spontaneous activity
- prolonged responses to known stimulus
- initiation of response from atypical site (brought on by sympathetics)
- injury induced increase in Na channels on the c-fiber (brought on by sympathetics)
what is ephaptic transmission
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.
what is ephaptic transmission the mechanism for
it is the mechanism for ALLOYDYNIA and REFERRED PAIN
what are the 3 general responses to nerve injury that cause pain
- sprouting/increased fiber density (i think this probably includes the neuromas that can occur)
- ectopic discharge/activity
- ephaptic transmission
