PAIN III: Neuropathic Flashcards
First pain is carried by
A-delta fibres
Second pain is carried by
C fibres
Neuropathic pain involves
Central sensitization
General characteristics of neuropathic pain
- Slow onset, long-lasting
- Hyperalgesia, Allodynia, Causalgia, Spontaneous Shooting Pain
- Sometimes involves sympathetic nervous system
- Often resistant to opioid analgesia
Why is neuropathic pain opioid resistant
downregulation of MORs
Neuropathic state and opioid-tolerant state have many similarities
Slow onset in Neuropathic pain
maybe months after initial injury
persists past healing
Alternate name for neuropathic pain
Disease of pain
Etiology of neuropathic pain–neuropathic pain induced by…
• Traumatic nerve, brain or spinal cord injury
• Amputation (Phantom Limb)
• Diabetic Neuropathy, Post Herpetic Neuropathy
(Shingles), HIV-AIDs or other infection, fibromyalgia
• Multiple Sclerosis
• Stroke (central pain)
How stroke can lead to neuropathic pain by
decreased blood supply in the pain pathway causing pain
Study of neuropathic pain–injury involve
damage to some but not all axons of a peripheral nerve
Central sensitzation
areas (of partial nerve injury) can become spontaneously active and drive further activity in higher centres
Pertubations at site of nerve injury leading to neuropathic pain
• Crushed axons degenerate and Schwann cells proliferate • Inflammatory mediators (interleukins, TNF-α, prostaglandins etc.) are released (exictes surviving sensory nerves and increase their excitability)
How inflammatory mediators at site of injury activate pain
crushed axons release inflam mediators –> these mediators directly excite surviving sensory nerves –> increased expression and function of Na channels decrease expression and function of K+ channels (increase excitability)
AND Promote de novo expression of CSF -1 (Colony stimulating factor 1)
Perturbations w/in the SC
- Activated primary afferents release glutamate, substance P, ATP and other mediators such as colony stimulating factor 1 (CSF-1)
- Increases activation of microglial cells (CNS macrophages)
- Microglia release further mediators (mainly BDNF)
Pertubations w/in SC (simple)
injury –> CSF-1 (etc.) release –> activate microglia –> BDNF release
Effects of Mediators from the microglia (released due to pertubations in the SC)
- Reduce inhibitory synaptic transmission (by GABAand glycine)
- Increase excitatory synaptic transmission (by glutamate on AMPARs and NMDARs)
- High concentrations of glutamate released during central sensitization favor the activation of NMDA receptors
Normal vs post-injury peripheral nerve
Normal: inhibitory neurons keep tactile info out of superficial lamina (where pain in signalling occurs)
Injured: loss of inhibit circuits –> tactile fibres leak into superficial lamina –> tactile stim will be interpreted as pain in brain –> allodynia
____ is responsible for initiation of central sensitization BUT ____ maintains it
microglia intitate; astrocyte proliferations maintains it
Why it’s hard to treat central sensitization
there are early and late mediators BUT doctors won’t see patients until it is well established with adtrocytic mediators
Would be easier to treat at start but you don’t have the pain then