Pain Management Part II Flashcards
chemical senses on neurons are sent via which type of receptors? (ion? G-coupled?)
ion channels or G coupled
mechanical and thermal senses on neurons are sent via which type of receptors? (ion? G-coupled?)
ion channels
initiation of a pain signal is conducted by what type of neurons?
primary afferent sensory neurons
what are the 3 primary pain NTs?
substance P, glutamate, and CGRP
primary afferent sensory neurons are:
a. Unipolar
b. Multipolar
c. Pseudo-unipolar
d. Bipolar
c
A alpha fibers:
Myelinated?
function?
sensitivity to block?
yes
motor and proprioception
low
A beta fibers:
Myelinated?
function?
sensitivity to block?
yes
touch
moderate
A delta fibers:
Myelinated?
function?
sensitivity to block?
yes
pain and temperature
high
C dorsal root fibers:
Myelinated?
function?
sensitivity to block?
no
pain, temp., and touch
very high
how does myelin affect a drug’s ability to block the sensory neuron?
makes it harder for drug to get into neuron
the activation of what receptor can block nociceptive receptors?
which 2 chemicals are agonists at this receptor?
TRPV1
capsaicin and resiniferatoxin
what do capsaicin and resiniferatoxin do?
they deplete substance P to disrupt neuronal function
what is strontium used for and how does it work?
it treats bone pain by entering in place of calcium to potentially reduce pain and inflammation
what class of drugs can we use for bone pain that are also primarily used for osteoporosis?
bisphosphonates
can we use calcitonin for bone pain management?
yes, but it is not efficacious
what is the channel target for local anesthetics?
to block voltage-gated sodium channels
local anesthetics have a high affinity for _____ channels, and thus ____ nerves are more affected by blockade
open, active
describe the use dependent blockade of local anesthetics (LA)
-LAs increase the refractory period of sodium channel
-they incr. threshold for depolarization
-each depolarization leads to more channel blockade
-eventual loss of excitability
which local anesthetics have a short duration of action?
procaine
chloroprocaine
lidocaine
mepivacaine
prilocaine
which local anesthetics have a medium duration of action?
benzocaine
cocaine
bupivacaine
which local anesthetics have a long duration of action?
etidocaine
ropivacaine
which two LAs are the only two without parental use?
benzocaine
cocaine
which LAs have topical usage?
benzocaine
cocaine
lidocaine
prilocaine
what CNS effects may occur with LA toxicity?
anxiety, nervousness, convulsions, drowsiness, and depressed breathing
what cardiovascular effects may occur with LA toxicity?
ventricular arrhythmia and collapse
how does increasing sensitization occur? (hyperalgesia)
-sensitizing chemicals are released from surrounding cells which lower the threshold for depolarization
- pain NTs are released with lower stimuli
-substance P activates the immune cells to release sensitizers creating a feedback loop
NSAIDs inhibit pain initiation by inhibiting synthesis of sensitizing _______
prostoglandins
what are potential neurologic SEs of NSAIDs?
dizziness and tinnitus
what effect does glutamate have when released by primary sensory afferents?
rapid depolarization
what effect does substance P/ CGRP have when released by primary sensory afferents?
sustained depolarization
transmission via primary afferent neurons is ______-dependent
calcium
A beta fibers synapse in which layers of the substantia gelatinoasa?
3,4,5
A delta fibers synapse in which layers of the substantia gelatinoasa?
1 and 2
C fibers synapse in which layers of the substantia gelatinoasa?
1,2,5
C fibers and A delta fibers in substantia gelatinoasa activate non-specific (NS) _______ neurons and ________
ascending, interneurons
what do NS ascending neurons do?
tell body where pain is located
C and A delta fibers also influence the activity of _____ secondary neurons
wide dynamic range (WDR)
what is the function of WDR axons?
transmit an intensity of pain message
paleospinothalmic polysynaptic neurons terminate in the _________ others reach the _______
brainstem, thalamus
neospinothalamic pathways mostly ascend directly to the ______ with a focused message of _____ _____________
thalamus, pain localization
A beta and A alpha fibers synapse in which layers of the substantia gelatinoasa?
3-5
T/F non-specific neurons only respond to pain
true
T/F wide dynamic range neurons respond to all sensations including pain
true
NE and 5-HT from descending reaction paths inhibit _____ or activate inhibitory __________ __________ to inhibit pain transmitter release and 2nd order pain transmission
WDRs, enkephalin interneurons
GABA/glycine send _______ signals to the WDR neuron
inhibitory
cytokines and PGs send ______ signals to the WDR neuron
activating
what is the “wind-up” theory causing chronic pain?
overtime there is increased glutamate release which leads to repeated depolarization leading to activation of NMDA Receptors
NMDA receptor activation makes the post-synaptic neurons more easy to depolarize
what is the theory of loss of inhibitory neurons causing chronic pain?
overstimulation of too much calcium activation can kill inhibitory neurons which will increase excitability/sensitization of relay neurons
what is the theory of spinal/central sensitization causing chronic pain?
immune cells released enhance NT release and lower depolarization threshold
what is allodynia?
touch or proprioception turns to pain sensation
REVIEW SLIDE 33!!!!
.
what drug class has synergistic effects with opioids which mediate spinal analgesic actions?
name the 2 we use
a2 agonists
clonidine, dexmedetomidine
why can SNRIs/TCAs be useful for pain?
NE activates a2 receptors
note: tramadol and tapentadol are reuptake inhibitors with some opioid agonism
.
CGRP receptor antagonists are used to treat?
migraines/headaches
GABA agents inhibit pain NT release and should inhibit pain transmission. What is the issue that makes them not effective at inhibiting pain?
they also inhibit inhibitory descending pathway
what drug is used for trigeminal neuralgia
carbamazepine
what drug is used off label for diabetic neuropathy?
Mexiletine
what is the mechanism of action of ketamine which is an NMDA receptor blocker?
blocking NMDA receptors will block wind up and treat chronic pain
what portion of the brain is the primary distributor of pain signals?
thalamus
