Peripheral mechanisms of pain Flashcards
“normal” pain is mediated by
A-delta & C fibers
pathological pain “hyperalgesia” is mediated by
peripheral and central sensitization
which fiber type makes up majority of cutaneous nociceptors?
C fibers (87%)
this nociceptor type is unmyelinated and very small
C fibers
this nociceptor type contains a limited neuropeptide content
A-delta fibers
nociceptive specific to noxious mechanical stimuli with limited response to thermal and heat
A-delta fibers
nociceptive specific to mechanical, chemical, thermal stimuli
C-fibers
nociceptor for “first pain” - fast, sharp, well localized
A-delta fibers
nociceptor for “second pain” - dull, burning, poorly localized
C fibers
this type of pain receptor can be found on odontoblasts and therefore has a possible role in tooth pain
TRP receptor
Trigeminal nerve branches with prominent chemesthesis
nasal - ethmoid
oral - nasopalatine
posterior palatine
lingual nerve
chemesthesis is mediated by:
TRP receptors
tooth pain fibers
A-delta & C fibers
dentinal tubules have what kinds of fibers?
A-delta fibers
Pulp chamber has what kind of fibers?
C fibers
A-delta fibers of dentinal tubules
extend a little into dentin tubules
contain CGRP
mechanical & thermal sensitivity
sharp pain
C-fibers of pulp chamber
dull, throbbing apin
contain Substance P
thermal sensitivity
chemosensitivity to inflammatory mediators
fiber type responds to algesic stimuli such as Bradykinin (BK)
pulp chamber C-fibers
A-delta fibers respond to which types of chemical stimuli?
NH4Cl and NaCl
C-fibers respond to which types of chemical stimuli?
Bradykinin (BK) and Histamine
Fibers respond mainly to inflammatory mediators
Pulpal C-fibers
theories of sharp pain
- neuron theory
- hydrodynamic theory
- odontoblast theory
smear layer for pain transduction
necessary to avoid pain when high pressure applied to dentinal tubules
used in root canal walls
EDTA does what?
dissolve smear layer = pain
odontoblast TRP thermoreceptors
TRPV1, 2, 3
TRPM8
TRPA1
odontoblast TRP mechanoreceptors
TRPV4
TRPM3
TRPP1, 2
purinergic signaling
part of odontoblast transducer theory
extracellular signaling mediated by purine nucleotides (adenosine, ATP)
Steps in odontoblast signaling
- depolarization by TRP receptors
- initiation of AP
- release of ATP via membrane channels
- afferent nerve response via P2X3 channels
P2X3
a type of nerve fiber found in pulp
present in both myelinated and unmyelinated pulpal nerve fibers
P2X3 receptors
nociceptive afferent nerve fiber
odontoblasts have what kinds of channels?
voltage gated Na+ channels
variety of TRP receptors can be found where?
odontoblasts
dentinal tubule innervating fibers
hyperalgesia
greater responsiveness to stimuli, allodynia
pain is prolonged and spontaneous
allodynia
response to non-painful stimuli produces pain
CGRP leads to
vasodilation and swelling
mechanical stimulus to C-fiber
Substance P leads to
mast cell > release histamine > stimulate C fiber
events after thermal or mechanical injury:
C-fiber releases substance P or CGRP > SP releases mast cells > histamine release > C fiber stimulated > CGRP leads to swelling > mechanical stimulus to C fiber
sensitize C-fibers rather than direct excitation
prostaglandins
cytokines
protons released from inflamed tissue that stim. vanilloid receptors
cytokines that sensitize C-fibers
interleukins, TNF
role of NGF in peripheral sensitization
induces local receptor trafficking
retrograde transport of signaling endosomes to promote gene expression
bind to high affinity TrkA receptor forming complex that sensitizes nociceptor
T/F? Prostaglandins directly depolarize neuron
false
TTX
fish substance that blocks sodium channels
A-fiber sodium channels are TTX _____ and potassium channels are ________
TTX sensitive ; Bradykinin
C-fiber sodium channels are TTX _______ and potassium channels are __________
TTX resistant ; Bradykinin and SK
prostaglandins block what channel
SK
Vanilloid receptor (TRPV1 or V1) lower threshold by:
- inflammatory mediators (BK and protons)
- Ca++ activated phosphorylation of VR1 receptor
- increase in # of receptors
neurogenic inflammation
substance P > histamine release
CGRP > swelling, vasodilation
direct stimulation of nociceptors
histamine (mast cells)
bradykinin (blood clotting)
5HT (platelets)
sensitization of nociceptors
prostaglandins (affect K+ channels)
proton release from inflamed tissue (TRPV1 vanilloid)
NGF (increases receptor trafficking)
mechanisms of hyperalgesia - allodynia
TRPV1 sensitization = lower temperature threshold
Prostaglandin sensitization= lower mechanical threshold
inflammatory mediators do what to peripheral stimulus
augment (add to) = greater response to painful stimuli, makes it prolonged and spontaneous
causalgia
burning pain
sympathetic nerve dystrophy
temperature induced pain
NGF secreted by
Schwann cells
promotes sprouting and regulates gene expression
NGF
NGF transported to
ganglion cell body
Schwann cells produce _______ for regenerating axons
laminin
ectopic discharge
- spontaneous activity
- prolonged response to known stimulus
- initiation of response from atypical site (ganglion)
- injury > increase in # Na+ channels
response to catecholamines
- activity evoked locally, not by normal receptor ending
ephaptic transmission is the mechanism for:
allodynia (pain response to nonpainful stimulus)
referred pain
sprouting
increased fiber density
induced by NGF
contain CGRP
dentinal tubule fibers
contain Substance P
pulpal fibers