Pain factors/suppressors

1. Damage to tissue releases proteolytic enzymes which liberate substances that excite peripheral nociceptors; these include histamine, prostaglandins, serotonin, potassium, kinins
2. Nociceptors release substances that enhance pain perception; the most studied of these is substance P which is released from nerve ending of C fibers in the skin during peripheral nerve stimulation; substance P causes release of histamine from cells
3. Stimulation of the periaqueductal gray produces a profound analgesia without altering behavior or motor activity; same observation is made with stimulation of the raphe magnus and paragigantocellularis
   1. these areas act by inhibiting neurons of laminae I, II and V of the dorsal horn
   2. periaqueductal gray has cell bodies containing substance P as do the spinal and cranial sensory ganglia, basal ganglia, and nucleus of the spinal trigeminal tract
4. opiates act pre and postsynaptically on neurons in laminae I and V suppressing afferent pain impulses from both A-delta and C fibers and can be reversed by naloxone
   1. injured nerves sprout A-delta and C fibers which are capable of spontaneous ectopic excitation and discharge and are also sensitive to locally applied or intravenous catecholamines; this may be the underlying cause of reflex sympathetic dystrophy
   2. naloxone can also reverse other forms of analgesia including stimulation of periaqueductal gray matter, acupuncture and placebo
5. endorphins (the morphine within)
   1. most studied are beta-endorphins (from the pituitary hormone beta-lipotropin), enkephalin and dynorphin
   2. found in greatest concentration in the midbrain
6. neuropathic pain
   1. pain arising from direct stimulation of nervous tissue exclusive of pain due to sensitization of C fibers (e.g. trigeminal neuralgia, herpes zoster, diabetes, trauma, arachnoiditis, spinal cord injuries, Dejerine-Roussy (thalamic pain – most commonly in the posterior thalamus))