Chronic pain Flashcards
Superficial sharp pain
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
Superficial dull, burning pain
Longer lasting - often “sore”
mediated through small, slowly conducting unmyelinated pain fibers (C fibers)
broad range of painful stimuli: mechanical, thermal, chemical
Deep/visceral pain
joints, muscles, bones, CT
aching sensation;difficult to localize
contraction of nearby skeletal muscle –> vicious cycle of increasing pain
unmyelinated C-fibers
Referred pain
pain perceived at a site adjacent to/at a distance from site of an injury’s origin
Unmyelinated C-fibers
mechanism unclear
Adelta fiber
synapse on laminae I or V in dorsal horn
can be localized more exactly
C-fiber
terminate in laminae II/III of dorsal
more difficult to localize
Pain receptor stimulation +/- tactile stimulation
very poorly localized without tactile stimulation
Adaptive pain
coupled with a noxious stimulus / healing tissue
Nociceptive/inflammatory
Nociceptive pain
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)
Inflammatory pain
increased sensitivity to prevent contact with/movement of injured part until repair is complete
Hyperalgesia
increased response to a normally painful stimuli
Allodynia
painful response to a normally benign stimulus
Maladaptive pain
uncoupled from a noxious stimulus/healing tissue
neuropathic/functional
Neuropathic pain
pain occurring in response to damage to nervous system
Shingles
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)
Post-herpetic neuralgia
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
FUnctional pain
pain occurring in response to abnormal operation of nervous system
Fibromyalgia
medicall unexplained
no cure
chronic widespread pain, allodynia
muscle/CT pain with many systemic problems
Peripheral sensitization
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
Kinins
e.g. bradykinin produced by proteolytic breakdown of kininogen in area of wound
most potent pain producing substance
Inflammatory chemicals involved in peripheral sensitization
Kinin
Substance P
Substance used elsewhere as synaptic transmitters: ACh, 5-HT
Substance P
can be released from peripheral terminals of sensory nerve fibers –> skin, muscle and joints
local inflammatory response
Post-translational processing of nociceptors
typically involve addition of phosphate groups
lower threshold/longer duration of opening
signals act locally
–> peripheral sensitization/early stages of primary hyperalgesia
takes minutes
Altered transcription of proteins made by nociceptors
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
Central sensitization
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
Acute phase of normal response to pain
Normal synaptic transmission via activation of AMPA receptors by glutamate
NMDA receptors are typically blocked by Mg
Acute phase of central sensitization
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
Windup
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
Persistent phase of central sensitization - gene regulation
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)
Persistent phase of central sensitization - disinhibition
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
Persistent phase of central sensitization - structural reorganization
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
Gate theory
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)
