peripheral mechanisms of pain Flashcards
what does the sensation of pain sense
Localization and intensity
what is the affective component of pain
Emotional response (psychological component)
what is acute pain
Short term pain witha n identifiable source
what is chronic pain
Long term pain with a frequently non-identified source
what nerves do Normal Pain
A-delta
C-fibers
what is pathological pain(hyperallgesia)
Peripheral and cental sensitization
- increased perception of pain
A-delta fibers make up what percent of cutaneous nociceptors
13%
size of A-delta fibers
Small and lightly myelinated
conduction veolcity of A-delta fibers
12-36m/s
Contenet of A-delta fibers
Limited neuropeptide contents
what type of channels are found on A -delta fibers
Na+ channels that are mainly TTX-sensitive
what are A-delta fibers nociceptive specific to
noxious mechaical stimuli
limited response to noxious heat, chemcial stimuli
what type of pain does A-delta fibers experience
1st pain
fast
sharp
well-localized
C fibers make up what percent of cutaneous nocicpetors
87%
size of C fibers
tiny .2-1.5 micrometers
unmyelinated
conduction velocity of C fibers
.5-1.2m/s
what is found within C fibers
many contain neuropeptides
channels of C fibers
Na+ channels both TTX-Sensitive (typical) and TTX-Resistance
Nocicetpive response of C fibers
Nociceptive specific to mechanical, chemical, thermal many polymodal (but not all noxious)
what type of Pain do C fibers sense
slow, dull, or burning, poorly localized pain
what kind of mechanoreceptors are fuond on A-delta fibers
High threshold mechanoreceptors: ENaCS (epithelial sodium channels) to play a role in mechanical nocicption
what receptors are found on Polymodal C-fibers
TRP receptors
what do TRP receptors respond for within pain
Polymodal characteristics that respond to thermal, chem, and mechanical stimuli
what does the Vanilloid receptor (TRPV1) respond to
capsaicin
heat (42 degrees Celsius)
protens
Stimulation of Vanilloid receptors (TRPV1) leads to
results in the influx of cations (Na and Ca)
how do Polymodal TRP receptors respond to different types of food
chemesthesis (extremes give Pain) middle give burning, tingling, astringency, pungency
what is chemesthesis
response of C-fibers (a few A delta) to chemical stimuli
is chemesthesis the same as taste/olfaction
NO
what did chemesthesis develop as
Part of a chemical defensive mechanism
- initiates expulsive reflexes such as coughing or sneezing
what kind of sensation is chemesthesis
produce both painful and non-painful sensations (burning, tingling (carbonation), astringency, pungency
nasal brnach of the trigeminal with chemesthesi
Ethmoid (ophthalmic)
oral branch of the trigeminal with chemesthesis
Posterior palatine
Nasopalatine (maxillary)
Lingual (Mandibular)
do polymodal nociceptors in the trigeminal system give the same response to different stimuli
No
what is the chemesthetic sensation of the ethmoid
sensitive to smell salts (ammonia)
what does Nociceptive specific mean
responds to 1 stimuli
how can olfaction and chemesthesia be activated
ORtho or restronaally
how is olfaction done
Olfactory receptors
what does Nasal chemesthesis
TRP receptors on ethmoid fibers
taste receptors on specialized olfactory epithelium cells
what are the taste receptsr on specialized olfactory epthelium cells
Single Chemosensory cells
where are single chemosensory cells found in the nose
scattered throughout nasal epithelium
what innervates single chemosensory cells
innervated by Vth nerve
what activates single chemosensory cells
Nasal
what does activation of single chemosensory cells lead to
initiates respiratory reflexes (apnea)
what is the transduction mechanism for single chemosensory cells
Via taste receptor mechansms
what receptors also are found on Vth fibers for chemesthesis
TRP receptors
relation between ethmoid nerve response and human perception
directly related
what primarily mediates Chemesthesi
TRP (some taste receptors in nasal peithelium)
threshold for chemesthesis
High threshold
sensations for chemesthesis
adversive sensations
what reflexes are activatd by chemesthsis
Removal reflexes (salivation, coughing, tearing, sneezing, apnea)
dental compounds and chemesthsis
can activated chemesthesis
possitive use of chemesthesis
Treatment for certain types of pain (postherpetic neuralgia, arthris)
how can capsaicin be used as a drug
exhibit desensitization since primary afferent nociceptors can become less reponsive following intense of repeated stimulation
how does capsaicin desnsitize primary affferent nocicptor mechanisms
Inactivation of voltage-gated ion channels
depletion of neuropeptides
where is eugenol found in nature
Cloves
uses of eugenol
Antiseptic, anti-inflammatory, analgesic effects
where is eugenol used in dental products
Zinc oxide eugenol: cement in pulp, capping, root canal filling
mouthwash and toothpaste
potential contraindications to using eugenol
allergic
harmful effect on dentin (cytotxic on pulp fibroblasts preventing collagen growth)
what receptors does Eugenol activate to produce its analgesic effects
TRP receptors (TRPV3) Inhibits voltage-gated Na and Ca channel in other class of C-fiber polymodal nocicpetors
what fibers are in dentinal tubules
A delta fibers extend .1- .2 mm into tubules
what does A delta fibers contain in dentinal tubules
calcitonin gene related peptide (CGRP) mechanical and thermal sensitivity
what does the A-dekta fibers in the Dentinal tubules sense
Mechanical and thermal sensitivity
exposed dentin from abrasion and lesions leads to sharp pain
what fibers are found in the pulp chamber
C-fibers
what is found in the C-fibers of the pulp chamber
Substance P
what does The C fibers in the pulp chamber sense
Thermal sensitivity
chemosensitivity to imflammatory mediators
imflammation leads to a dull throbbing pain
does Dentinal A-delta fibers respond the same to mechanical forces
different response to different mechanical forces
can Dentinal A-fibers respond to temp
yes, and even responds to temp not in the pain range, but will still give a sharp pain
thermal sensitivity of C-fibers (latency, conduction speed, response to cold)
Long latency
Slow conduction
response to cold in the pain range
Pulpal c-fibers responding to inflammatory mediatory Bradykinin leads to waht latency
long latency
what does C-fibers respond to and produce
Respond to inflammatory mediators and thermal stimuli
produces dull/throbbing pain
what does A-delta fibers in dentinal tubules respond to and produce
mechanical, thermal, chemical stimuli applid to cavity
-sharp pain
the three theories of sharp pain
Neuron theory
Hydrodynamic theory
Odontoblast theory
how does the neuron theory for thermal pain work
Thermosensitivie TRP receptors found on A-delta fibers
Could respond to thermal changes via dentinal fluid
how does the hydrodynamic activation of nerve fibers work
Possible low threshold mechanoreceptors are found on A-delta fibers
Could act as a transducer for thermal osmotic mechanical effectors on dentinal fluid
Afferent Mechanoreceptors for Hydrodynamic activation of nerve fibers
TRPV1 (osmoreceptor) TRPV2 TRPA1 Piezo2 ENaC
how could the odnotoblast act as a sensory cell
Odontoblast has process in dentinal tubules
Fluid flow by osmotic, thermal and mechanical stimuli could impact odonotoblast
Odontoblast thermoreceptors
TRPV1 (greater than 43) TRPV2 (greater than 52) TRPV3 (33-39) TRPM8 (less than 25) TRPA1 (less than 17)
what odonotblast TRP receptor may have possible mechanoreceptor activation
TRPV4
Hypothetical steps in Odontoblast signalling to act as a receptor cel
Depolarization by various TRP receptors
Initiation of AP
RElease of ATP (possibly non vesicular) via membrane channels
Afferent nerve response via P2X3 receptors
what channels are found on Odontoblasts
Voltage gated Na+ channels
where are TRP receptors found for sharp dentinal pain
Both odontoblast and fibers innervating dentinal tubules
what explains temperature-induced sharp pain in dentition
Temperature sensitive TRP channels on nerve endings and odontobasts
what exaplins mechanotransduction of pain by dentinal fluid movement (hydrodynamic theory
Piezo2 receptors on nerve endings
What can odontoblast signal
thermal and possibly mechanical stimulation but synapse to afferent nerve not proven
what is hyperalgesia
Greater responsiveness to stimuli
spontaneous pain
prolonged pain
allodynia
response to non-painful stimuli produce pain
what happens when there is thermal or mechanical injury
C-fiber response and release neuropeptides substance P and CGRP
substance P stimulates mast cells
mast cells release hiatmine
stimulate C fiber
CGRP leads to vasodilation and swelling
this gives mechanical stimulus to C-fiber
what happens when there is damages that causes bleeding
same factors as thermal and mechanical stimulation
Clot formation
bradykini
stimulates C fiber
Platet products from blood 5-HT (serotonin)
stimulates C fiber
Damages leading to infection and immune response can cause what senastion
sensitization (increased sensitiive of a neuron to a given stimulus
how does infection and immune response lead to sensitization
Prostaglandins sensitive C fiber rather than cause direct excitation
cytokines (interleukins, tumer necrosis factor) also sensitive C fibers
Protons released in inflamed tissue stimulate vanilloid (TRPV1) receptors and produce sensitization
how does prostaglandins affect a neuron
does not directly depolarize the neuron but instead leads it to more likely respond to a sensation
how does prostaglandins work
Block SK channel
NA+ channels can have a lowered threshold
how did we discover how porstaglandins work
used TEtrodotoxin ( a puffer fish venom that block some Na channels)
effect of Inflammation on the Vanilloid Receptor
inflammation leads to lower threshold (22 degrees instead of 42)
Mechanism of sensitization of Vanilloid receptor
Presence of inflammatory mediators (bradykinin and protons) lower threshold
increased intracellular CA++
CA++ activated phosphorylation of TRPV1 increases sensitivity
how does CA++ enter during the sensitization of the Vanilloid Receptor
CA++ through receptor
GPCR can increase intracellular Ca++
how can peripheral sensitization occur
NEurogenic Inflmmation via release of algesics
Direct stimulation of nocicpetors
Sensitization of nociceptors
how can neurogenic Inflammation occure in peripheral sensitzation
Subatnce P (from nocicptor itself) stimulates hiatmine relase CGRP produces swelling (mech stimulus)
what objects are invovled in direct stimulation of nociceptors
Histamine (mast cells)
Bradykinin (Blood clotting)
5_HT (Blood platelets)
what chemicals can lead to sensitization of nociceptors for peripheral sensization
Prostaglandins (Effect on K+ (SK) channels)
proton relase in inflamed tissue (TRPV1)
How can neurons resppond to non-painful stimuli to produce pain
sensitization of TRPV1 lowered temp threshold
Sensitization by prostaglandins lowered mechanical threshold
how can neurons response to painful stimuli greater
Action of inflammatory mediators augments peripheral stimulus
how can pain become spontaneous and prolonged
action of inflammatory mediators act as peripheral stimulus
Causalgia
Burning pain
allodynia
Light touch leading to pain
Sympathetic nerve dystrophy
Mild temperature induced pain
Phantom sensation
sensation in denervated tissue
nerve damage can lead to what types of pain
Causalgia
Allodynia
Sympathetic nerve dystrophy
Phantom sensations
what causes neuromas
regenerative capacity of nerves leading to an unorganized mass of nerve tissue due to sprouting and collateral sprouting of injured and uninured fibers
effect of neuromas
sometimes but not always painful
can schwann cells devide
Yes
what do schwann cells do to help with regenerating axons
PRoduce laminin for substrate for regenerating axons secrete NGF (nerve growth factor)
where is NGF transported
to ganglion cell body
roll of NGF
regulates gene expression and promotes sprouting
what genes does NGF regulates
Microtubules and microfilaments
neurotransmitter production
ion channels
receptors
Ectopic dischage from a C-fiber response
Spontaneous activity
Prolonged responses to known stimulus
Ectopic dischage from a C-fiber initation
Initiation of resposne from atypical site (ganglion)
Ectopic dischage from a C-fiber result
results from injury-induced increase in Na+ channels
Ephaptic transmission
A beta fiber acts on the C fiber
Ephaptic transmission is a mechanism for what
for allodynia
and referred pain
how is ectopic dischage evoked
Locally, not by normal receptor ending (more Na channels and response to catecholamines)
