Prostaglandins inhibit endogenous pain control mechanisms by blocking transmission at spinal noradrenergic synapses.
Spinal intrathecal injections of the nonsteroidal antiinflammatory analgesics (NSAIAs) indomethacin and acetylsalicylic acid, which inhibit prostaglandin synthesis, cause dose-dependent hypoalgesia in the rat. Intrathecal injections of prostaglandin-E2 (PGE2) produce dose-dependent hyperalgesia. To determine whether this action of prostaglandins on the central nervous system is mediated through pain-generating or analgesia pathways, we studied the effect of intrathecal PGE2 on endogenous opioid-induced analgesia. Intrathecal PGE2 antagonized the analgesia produced by both brain stimulation and intracerebroventricular morphine. In contrast, the NSAIAs synergized with brain stimulation and morphine-induced analgesia. The alpha-adrenergic antagonist phentolamine and the catecholaminergic selective neurotoxin 6-hydroxydopamine, used to block tonic catecholamine activity in endogenous opioid-mediated analgesia systems, prevented the hyperalgesia induced by intrathecal PGE2. Phentolamine did not, however, block the hyperalgesia caused by intradermal PGE2. These findings suggest that prostaglandins can block endogenous opioid-mediated analgesia systems by inhibiting the bulbospinal noradrenergic component of this analgesia pathway.
Taiwo
Y O
YO
Department of Medicine, University of California, San Francisco 94143.
Levine
J D
JD
D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology*; D010646:Phentolamine / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000166:cytology*; D013569:Synapses / Q000166:cytology*; D009435:Synaptic Transmission / Q000187:drug effects*
D011453:Prostaglandins; D011458:Prostaglandins E; D009020:Morphine; D015232:Dinoprostone; D001241:Aspirin; D007213:Indomethacin; D010646:Phentolamine