Mediation of primary afferent peripheral hyperalgesia by the cAMP second messenger system.
Cyclooxygenase (prostaglandin E2 and prostaglandin I2) and lipoxygenase [8(R), 15(S)-dihydroxyicosa-(5E-9,11,13Z)-tetraenoic acid] products of arachidonic acid metabolism are thought to produce peripheral hyperalgesia by a direct action on the primary afferent nociceptor. In this study we investigated the possibility that these eicosanoids generate hyperalgesia through a common second messenger in the rat. We report that 8-bromo cAMP, a membrane permeable analogue of cAMP, produces a dose-dependent hyperalgesia that is not affected by treatments that interrupt indirect routes of hyperalgesia production including sympathectomy with 6-hydroxydopamine, depletion of polymorphonuclear leukocytes (a source of hyperalgesic eicosanoids) with hydroxyurea, or blockade of the cyclooxygenase pathway of arachidonic acid metabolism with indomethacin. The phosphodiesterase inhibitor isobutyl-methylxanthine markedly prolongs the hyperalgesic effect of 8-bromo cAMP as well as those of the directly acting hyperalgesic agents prostaglandin E2, prostaglandin I2 and 8(R),15(S)-dihydroxyicosa-(5E-9,11,13Z)-tetraenoic acid. We conclude that the effect of all known hyperalgesic eicosanoids is mediated by the cAMP second messenger system and suggest, therefore, that cAMP mediates peripheral hyperalgesia in primary afferent nociceptors.
Taiwo
Y O
YO
Department of Medicine, University of California 94143-0724.
Bjerknes
L K
LK
Goetzl
E J
EJ
Levine
J D
JD
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology*; D006930:Hyperalgesia / Q000139:chemically induced* / Q000378:metabolism; D006941:Hyperesthesia / Q000139:chemically induced*; D008297:Male; D010525:Peripheral Nerves / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D015290:Second Messenger Systems
D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP