title: Prostaglandins inhibit endogenous pain control mechanisms by blocking transmission at spinal noradrenergic synapses.
abstract: 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.
authors.affiliation: Department of Medicine, University of California, San Francisco 94143.
authors.forename: Y O
authors.initials: YO
authors.lastname: Taiwo
authors.forename: J D
authors.initials: JD
authors.lastname: Levine
mesh_terms: 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*
chemical_list: D011453:Prostaglandins; D011458:Prostaglandins E; D009020:Morphine; D015232:Dinoprostone; D001241:Aspirin; D007213:Indomethacin; D010646:Phentolamine