Chronic pain

Question 1

Superficial sharp pain

Answer 1

sensed with a little delay
usually short in duration
mediated by myelinated pain fibers (Adelta fibers)
Conduct AP btw 5-30 m/sec (medium speed)
Responds to either mechanical or temperature stimuli

Question 2

Superficial dull, burning pain

Answer 2

Longer lasting - often “sore”
mediated through small, slowly conducting unmyelinated pain fibers (C fibers)
broad range of painful stimuli: mechanical, thermal, chemical

Question 3

Deep/visceral pain

Answer 3

joints, muscles, bones, CT
aching sensation;difficult to localize
contraction of nearby skeletal muscle –> vicious cycle of increasing pain
unmyelinated C-fibers

Question 4

Referred pain

Answer 4

pain perceived at a site adjacent to/at a distance from site of an injury’s origin
Unmyelinated C-fibers
mechanism unclear

Question 5

Adelta fiber

Answer 5

synapse on laminae I or V in dorsal horn

can be localized more exactly

Question 6

C-fiber

Answer 6

terminate in laminae II/III of dorsal

more difficult to localize

Question 7

Pain receptor stimulation +/- tactile stimulation

Answer 7

very poorly localized without tactile stimulation

Question 8

Adaptive pain

Answer 8

coupled with a noxious stimulus / healing tissue

Nociceptive/inflammatory

Question 9

Nociceptive pain

Answer 9

acute pain caused by a noxious stimulus
can be produced by direct mechanical deformation of nocicepter
OR activation of specific channels such as TRPV (cold/heat)

Question 10

Inflammatory pain

Answer 10

increased sensitivity to prevent contact with/movement of injured part until repair is complete

Question 11

Hyperalgesia

Answer 11

increased response to a normally painful stimuli

Question 12

Allodynia

Answer 12

painful response to a normally benign stimulus

Question 13

Maladaptive pain

Answer 13

uncoupled from a noxious stimulus/healing tissue

neuropathic/functional

Question 14

Neuropathic pain

Answer 14

pain occurring in response to damage to nervous system

Question 15

Shingles

Answer 15

VZV dormant following chicken pox
Reactivated virus migrates from DRG along nerves to spinal cord and skin
Painful blisters (crust over, heal in 4-6 weeks)

Question 16

Post-herpetic neuralgia

Answer 16

continuation of pain long after the rash and blisters heal
Occur from nerve damage caused by virus
Burning, stabbing, gnawing
20% of patients with shingles

Question 17

FUnctional pain

Answer 17

pain occurring in response to abnormal operation of nervous system

Question 18

Fibromyalgia

Answer 18

medicall unexplained
no cure
chronic widespread pain, allodynia
muscle/CT pain with many systemic problems

Question 19

Peripheral sensitization

Answer 19

reduction in threshold/increase in responsiveness of nociceptors
e.g. heat sensitivity after a sunburn
Inflammatory chemicals/mediators released around site of tissue damage –> alter nociceptive receptors/ion channels, increase excitability
1) post-translational processing
2) altered transcription

Question 20

Kinins

Answer 20

e.g. bradykinin produced by proteolytic breakdown of kininogen in area of wound
most potent pain producing substance

Question 21

Inflammatory chemicals involved in peripheral sensitization

Answer 21

Kinin
Substance P
Substance used elsewhere as synaptic transmitters: ACh, 5-HT

Question 22

Substance P

Answer 22

can be released from peripheral terminals of sensory nerve fibers –> skin, muscle and joints
local inflammatory response

Question 23

Post-translational processing of nociceptors

Answer 23

typically involve addition of phosphate groups
lower threshold/longer duration of opening
signals act locally
–> peripheral sensitization/early stages of primary hyperalgesia

takes minutes

Question 24

Altered transcription of proteins made by nociceptors

Answer 24

Signals transported back to cell body of sensory neurons in DRG
–> change txn or tln
Increased protein shipped back to terminal –> increased responsiveness of terminal to stimuli
–> peripheral sensitization/ early stages of primary hyperalgesia

Happens in ~1 day

Question 25

Central sensitization

Answer 25

increase in excitability of neurons within CNS
–> normal inputs produce abnormal responses

Hyperresponsive conditions of: post-op pain, migraine, neuropathic pain, fibromyalgia, GI tract pain

Question 26

Acute phase of normal response to pain

Answer 26

Normal synaptic transmission via activation of AMPA receptors by glutamate
NMDA receptors are typically blocked by Mg

Question 27

Acute phase of central sensitization

Answer 27

1) Summation of synaptic inputs from activation of nociceptors
2) removal of Mg block of NMDA receptors –> increased sensitivity to glutamate
3) postsynaptic receptors are phosphorylated
- increased recruitment to synaptic membrane
- increased receptor kinetics (longer opening)
- decreased opening threshold

get WINDUP

Question 28

Windup

Answer 28

progressive increase in discharge of dorsal horn neurons in response to repeated low-frequency activation of nociceptors

can be decreased by using ketamine (competitive NMDA blocker) at a low dose

Question 29

Persistent phase of central sensitization - gene regulation

Answer 29

Upregulation of genes encoding receptors locally
Upregulation of genes globally:
- COX-2
- initiated by a circulating factor released by inflammatory cells –> increase of PGE2 –> facilitate synaptic transmission and excitability

Widespread induction of COX-2: generalized aches/pains, loss of appetite, changes in mood and sleep cycle (features of inflammatory diseases)

Question 30

Persistent phase of central sensitization - disinhibition

Answer 30

Inhibitory interneurons in spinal cord normally act to produce a limited, appropriate and brief response to any input
Disinhibition increases excitability and pain
Tx aimed at preventing loss of these interneurons

Question 31

Persistent phase of central sensitization - structural reorganization

Answer 31

Following nerve injury vacant synapse sites
A/beta fibers sprout and form novel synapses in lamina II –> inappropriate functional connections –> persistent hypersensitivity and phenotype conversion

Question 32

Gate theory

Answer 32

Transmission of pain from peripheral nerve through spinal cord can be modulated by:

• other afferent neurons
• controls emanating from brain

effect of transcutaneous electrical stimulation thought to be due to this effect (stimulate Abeta fibers, reduce flow of pain info to the brain)