Alpha 1-adrenoceptor-mediated sympathetically dependent mechanical hyperalgesia in the rat.
The model of rolipram (a type IV phosphodiesterase inhibitor) induced prolongation (> 3 days) of the mechanical hyperalgesia produced by the intradermal injection of prostaglandin E2 in the hairy skin of the hindpaw of the rat, measured by the Randall-Selitto paw-withdrawal test, was employed to study mechanisms involved in the contribution of the sympathetic postganglionic neuron to mechanical hyperalgesia. Lumbar surgical sympathectomy prevented rolipram-induced prolongation of prostaglandin E2 hyperalgesia. Decentralization of sympathetic postganglionic neurons innervating the hindpaw did not, however, effect rolipram-induced prolongation of prostaglandin E2 hyperalgesia. Phentolamine, an alpha-adrenoceptor antagonist, and prazosin, an alpha 1-selective adrenoceptor antagonist, when given systemically or intradermally at the site of injection of prostaglandin E2 and rolipram, blocked rolipram-induced prolongation of prostaglandin E2 hyperalgesia. Intrathecal administration of phentolamine and prazosin were, however, without effect on rolipram-induced prolongation of prostaglandin E2 hyperalgesia. Yohimbine, an alpha 2-adrenoceptor antagonist given systemically, intradermally or intrathecally also did not produce any alteration in rolipram-induced prolongation of prostaglandin E2 hyperalgesia. We propose that sympathetic postganglionic neurons are involved in rolipram-induced prolongation of prostaglandin E2 hyperalgesia and that this form of sympathetically dependent hyperalgesia, which is independent of activity in preganglionic sympathetic neurons, is mediated by a peripheral alpha 1-adrenergic mechanism.
Ouseph
A K
AK
Department of Anatomy, University of California, San Francisco 94143-0452, USA.
Levine
J D
JD
D058646:Adrenergic alpha-1 Receptor Agonists; D000818:Animals; D001338:Autonomic Fibers, Postganglionic / Q000187:drug effects; D001339:Autonomic Fibers, Preganglionic / Q000187:drug effects; D015232:Dinoprostone / Q000494:pharmacology; D006930:Hyperalgesia / Q000503:physiopathology*; D007278:Injections, Spinal; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010147:Pain Measurement / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010812:Physical Stimulation; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects*; D020889:Rolipram; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000166:cytology / Q000503:physiopathology*
D058646:Adrenergic alpha-1 Receptor Agonists; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D018340:Receptors, Adrenergic, alpha-1; D020889:Rolipram; D015232:Dinoprostone