what are the dimensions of pain?
1) Acute vs. Chronic
2) Sensation of pain vs affective component
3) “Normal” vs Pathological Pain
what is the difference between pain sensation and the affective component?
sensation= Localization and intensity
affective component= Emotional response (psychological component)
how is “normal” pain mediated? how is pathological pain mediated?
“normal” pain- A-delta and c-fiber mediated
pathological pain- Peripheral & central sensitization
basic characteristics of A-delta fibers:
makes up 13% of cutaneous nociceptors
Small & lightly myelinated
responds to noxious mechanical stimuli
its the “1st pain- sharp and localized”
basic characteristics of C fibers
makes up 87% of cutaneous nociceptors
tiny & unmyelinated
responds to varied stimuli, many POLYMODAL (but all noxious)
its the “2nd pain- slow, dull or burning, poorly localized”
Both ______ channels and _____ receptors play a role in Pain transduction
ENaCS :(epithelial sodium channels)
TRP (transient receptor potential) receptors
T/F: Some “Pain”/nociceptor TRP channels also have Chemosensitivity
true
Chemesthesis is the response of _______ to chemical stimuli
c-fibers
what sensations are associated with chemesthesis
Burning & tingling
e.g.
salt water on an open wound
Chili peppers in food (capsaicin)
what does the Vanilloid Receptor (TRPV1 or V1) respond to? what does it trigger?
Responds to:
1. capsaicin 2. heat (42 degrees C) 3. protons
stimulation results in influx of cations (Na+ and Ca2+)
which branches of the Trigeminal nerve contains prominent chemesthesis sensation?
Nasal branch:
1) ethmoid
Oral branch:
1) Posterior palatine
2) Nasopalatine nerve
3) LINGUAL NERVE
Chemesthesis is Mediated by ______ receptors
TRP
Chemesthesis predominately transmits ______ sensations
aversive
e.g. burning, tingling
probably not “banana” or “salty”
dentinal tubules are occupied by which type of nerve fibers? What type of sensation are they responsible for?
A-delta fibers
- contain calcitonin gene related peptide (CGRP)
- mechanical & thermal sensitivity
- sharp pain
the pulp chamber is filled with which type of nerve fiber? what sensation is it responsible for?
C fibers
contain Substance P (SP)
thermal sensitivity
chemosensitivity to inflammatory mediators
dull throbbing pain
within the tooth, _______ fibers respond to algesic stimuli such as bradykinins
C fibers
-has a long latency
which dentinal fibers respond to temperature?
Dentinal A-fibers AND C-fibers can Respond to Temperature
The sensation from this stimulation is sharp pain in the dentin tubules, throbbing pain in the C-fibers
high pressure applied to dentinal tubules does not cause pain, unless what happens?
EDTA dissolves smear layer
THEN pressure causes pain
T/F: there is communication between odontoblasts
and nerve terminals
False
Communication has not been demonstrated
what is the physiological evidence that supports the hydrodynamic theory?
A-delta fibers respond to mechanical, thermal,osmotic stimuli
Odontoblast may act as mechanoreceptor cell
what are the characteristics of Hyperalgesia?
- greater responsiveness to stimuli
- pain is spontaneous
- pain is prolonged
what is allodynia?
response to non-painful stimuli produce pain
___________ Mediators Affect Nociceptive Neurons
Inflammatory Mediators
which inflammatory mediators directly stimulate nocioceptors?
histamine
bradykinin
5-HT
which inflammatory mediators stimulate other cells to release algesics?
substance P: (from the nociceptor itself) stimulates histamine release
bradykinin: increases histamine release (mast cells)
_________ are inflammatory mediators involved in sensitization
prostaglandins
how does inflammation increase the sensitivity of the Vanilloid Receptor (TRPV1 or V1)
- Ca++ activated
phosphorylation of VR1 receptor (TRPV1) - Increase in receptor number
- Presence of inflammatory mediators (e.g.bradykinin & protons)
Sensitization of TRPV1 lowers the ___________ threshold
temperature
Sensitization by prostaglandins lowers the ___________ threshold
mechanical
Pain Pathophysiology associated with Nerve Damage:
1) Causalgia
2) Allodynia
3) Sympathetic nerve dystrophy - temperature induced pain
4) Phantom sensations - sensation in denervated tissue
Neuromas are caused by what?
collateral sprouting of nerve branches
can be painful
what are the characteristics of C-fiber ectopic discharge?
A) Spontaneous activity
B) Prolonged responses to known stimulus
C) Initiation of response from atypical site
**Results from injury-induced increase in Na+ channels
Ephaptic Transmission is a mechanism for which 2 conditions?
mechanism for allodynia and referred pain
what are the mechanisms for peripheral sensitization?
- Decreased threshold
- Pain is spontaneous & prolonged
- Ectopic discharge – (abnormal activation)
what is the mechanism for ectopic discharge?
more Na+ channels following nerve injury
response to catecholamines following nerve injury
Ephaptic response due to increased Na+ expression
_________ will increased number and type of receptors after nerve damage
demyelination
T/F: Chemesthesis has a higher threshold for chemosensitivity than our sense of smell
true
what is chemesthesis mediated by?
TRPV1 (V1) receptors
Pain Perception Varies with ___________ Density
innervation
what is TRPV1 sensitive to? What about TRPA1?
TRPV1:
- capsaicin
- noxious heat (above 42 degrees C)
- protons
TRPA1: mustard oil, wasabi, garlic, noxious cold
Lingual Chemesthesis (common chemical taste) is sensed by what type of fibers?
Trigeminal polymodal nociceptors (c-fibers)
TRP receptors found on trigeminal sensory fibers respond to chemicals by mediate _________
chemesthesis
what types of ion channels are found in the odontoblast?
1.TRP channels (TRPM3 and TRPV4)
sensitive to mechanical stimulation
- Voltage-gated Na+ channels
(odontoblasts can generate action potentials)
what neuropeptides do c-fibers release during thermal or mechanical injury?
releases neuropeptides substance P (SP) or CGRP
T/F: Prostaglandins can stimulate a neuron
FALSE- Prostaglandins do not stimulate neuron
they lower its threshold to stimuli- sensitize the neuron
what is the effect of CGRP being released from c-fibers?
vasodilation and swelling (mast cell activation)
from a mechanical activation of C-fibers
_______ will stimulate c-fibers after an injury that causes bleeding
Bradykinin
there is a upregulation of Na+ channels following what?
nerve damage sprouting
how can the threshold limit for a nerve cell be lowered?
TRPV1- temperature threshold lowered by inflammation
Prostaglandins lower mechanical threshold via SK K+ channels
which type of C-fiber will respond to only 1 type of nociceptive stimuli:
e.g. chemical, or thermal or mechanical only
non-polymodal
what are trigeminal polymodal nocioceptors (c-fibers) sensitive to?
- different spices
- high concentrations of salt