B7.004 Mechanisms of Pain and Analgesia

Question 1

definition of pain

Answer 1

an unpleasant sensory and emotional experience which we primarily associate with tissue damage or describe in terms of such damage, or both

Question 2

classification of nociceptive pain

Answer 2

proportional to intensity of stimulation of the nociceptor (stimulus dependent)
when acute:
-physiologic pain
-serves a protective function
-"normal pain"

Question 3

classification of inflammatory pain

Answer 3

lowered threshold for stimulation of the nociceptor

• peripheral pathology / sensitization
• adaptive / protective mechanism
• healing / repair - pathological

Question 4

classification of neuropathic pain

Answer 4

sustained by aberrant processes or damage in PNS or CNS
disproportional to intensity of nociceptor stimulation
serves no protective/adaptive function
pathologic pain

Question 5

classification of nociplastic pain

Answer 5

stimulus independent
no inflammation
no structural neuronal damage
produced as a result of central plasticity/sensitization
serves no protective / adaptive function
pathologic pain (often body wide)

Question 6

classification of mixed pain

Answer 6

nociceptive and neuropathic components

ex: failed low back surgery syndrome, complex regional pain syndrome

Question 7

classification of idiopathic pain

Answer 7

no underlying lesion
pain disproportionate to degree of clinically discernable tissue injury
largely replacement by “nociplastic” terminology

Question 8

2 components of nociceptive stimulus

Answer 8

sensory / discriminative component
emotional component
-affective: motivational
-cognitive: evaluative

Question 9

characteristics of the sensory/ discriminative component of nociceptive pain

Answer 9

location
intensity
modality
transmitted via the neospinothalamic tract (VPL)

Question 10

characteristics of the emotional component of nociceptive pain

Answer 10

negative impact on affect/mood
chronic pain can lead to depression
transmitted by paleospinothlamic tract (limbic/brainstem)

Question 11

hyperalgesia

Answer 11

stimulus that usually produces a mild pain will now produce much more pain

Question 12

allodynia

Answer 12

formerly innocuous stimulus will now produce pain

Question 13

peripheral events associate with pain

Answer 13

tissue injury
inflammation
recruitment of immune mediators

Question 14

activation of nociceptors

Answer 14

direct activation (K+, ATP)
recurrent activation of terminal branches (SP, CGRP)
indirect activation (bradykinin, histamine)

Question 15

describe how nociceptors can be both afferent and efferent in function

Answer 15

when stimulated, nociceptors send out a signal in all directions
a portion of the signal travels to the CNS (afferent)
additionally, a portion of the signal will cause recurrent activation of adjacent neuron branches
recurrent activation stimulates release of vesicular contents of these nerve terminals (peptides like SP and CGRP and glutamate), this is efferent action
5-7x more neurotransmitters released in periphery as in CNS after nociceptive stimulus

Question 16

triple response of Lewis

Answer 16

redness at injury (vasodilation)
edema (increased vascular permeability)
spreading redness around injury (axonally mediated reflex vasodilation)
work together to produce pain and heat

Question 17

how do peripheral changes sensitize nociceptors

Answer 17

nociceptors:
-increased neurotransmitter / peptide / GF production
-stimulation of nerve terminal growth
lowered threshold for activation
unmasking of "silent" nociceptors

Question 18

phenomenon of peripheral sensitization

Answer 18

primary hyperalgesia

Question 19

process of central sensitization

Answer 19

prolonged activation of nociceptors and projection pathways
recruitment of adjacent neurons
changes in central pharmacology

Question 20

phenomenon of central sensitization

Answer 20

secondary hyperalgesia
includes peripheral and central events
represents plasticity of neuronal systems
can produce long term pathophysiology

Question 21

discuss the changes in central pharmacology that result in central sensitization

Answer 21

NMPA receptors for glutamate are always open
initial depolarization leads to short term sensitization and the opening of NMDA channels
eventually excess kinase activation leads to phosphorylation of regulatory proteins and altered gene expression which lead to long term sensitization

Question 22

mechanisms of pathologic pain

Answer 22

pain processing mechanisms function abnormally (nociplastic)
nociception is sustained by chronic injury (inflammatory)
peripheral processes:
-injured or diseased neurons (neuropathic)
-growth of axonal sprouts
-formation of ectopic foci

Question 23

common persistent pain syndromes

Answer 23

chronic inflammatory pain
neuropathic pain (cancer, PHN)
central pain (CVA, plasticity)
radicular pain (nerve branch)
phantom limb pain (amputation)
complex regional pain syndrome
referred pain (visceral-cutaneous)

Question 24

categories of analgesic drugs

Answer 24

nonopioid analgesics
opioid analgesics
adjuvant analgesics (neuropathic pain)
drugs for headache (triptans)

Question 25

how do adjuvant analgesics work

Answer 25

decrease unwanted electrical activity in injured neurons

Question 26

most common inhibitory neurotransmitter

Answer 26

GABA

Question 27

peptides and receptors that modulate endogenous analgesia

Answer 27

opioid peptides
-enkephalin
-endorphin
-dynorphin
opioid receptors
-mu, delta, kappa

Question 28

when does the endogenous analgesic system function

Answer 28

stress or stimulus produces

Question 29

sites of action of opioid analgesics

Answer 29

primary: brainstem / medullary centers
-periaqueductal gray matter
-nucleus raphe magnus
limbic system
spinal cord
periphery