Behavioral and autonomic correlates of the tactile evoked allodynia produced by spinal glycine inhibition: effects of modulatory receptor systems and excitatory amino acid antagonists.
Intrathecal administration of glycine (strychnine) or GABA (bicuculline) but not opioid (naloxone), adrenergic (phentolamine) or serotonin (methysergide) receptor antagonists resulted in a dose-dependent organized agitation response to light tactile stimulation. This effect was maximally evoked by oscillating but not continuous stimulation applied to a dermatome corresponding to the levels of spinal cord acted upon by the intrathecal antagonist. Similar results were observed in chloralose-urethane anesthetized rats in which tactile stimulation evoked hypertensive responses following local tactile stimuli. The effects were only mildly depressed by even high doses of spinal morphine or DADL and not at all by ST-91 or baclofen. In contrast, intrathecal injections of glutamate receptor antagonists resulted in a dose-dependent depression of the strychnine evoked hyperesthesia with the ordering of activity being MK-801, AP-5, kynurenic acid, SKF10047 and ketamine. At doses below those which produced motor dysfunction, however, these agents had no effects on the hot-plate response latency. These data emphasize that low threshold afferent input is likely subject to an ongoing modulation, the loss of which results in a miscoding of the afferent stimulus yielding a pain relevant message. The lack of effect of agents having a powerful effect on somatic pain stimuli and the converse effects of glutamate receptor antagonists on the strychnine hyperesthesia at doses which do not affect the somatic pain response indicate discriminable processing systems, the characteristics of which resemble the clinical phenomenon observed in patients suffering from sensory dysesthesia following central and peripheral horn injury.
Yaksh
Tony L
TL
Department of Pharmacology and Laboratory of Neurosurgical Research, Mayo Clinic, Rochester, MN 55905 U.S.A.
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D001640:Bicuculline / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D013331:Strychnine / Q000494:pharmacology*
D000700:Analgesics; D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter; D013331:Strychnine; D001640:Bicuculline