title: Sex hormones regulate the contribution of PKCepsilon and PKA signalling in inflammatory pain in the rat.
abstract: We have evaluated the contribution of differences in second messenger signalling to sex differences in inflammatory pain and its control by sex hormones. In normal male but not female rats, epinephrine-induced mechanical hyperalgesia was antagonized by inhibitors of protein kinase Cepsilon (PKCepsilon), protein kinase A (PKA) and nitric oxide synthetase (NOS). Similarly, in PKCepsilon knockout mice, a contribution of PKCepsilon to epinephrine-dependent mechanical hyperalgesia occurred in males only. In contrast, hyperalgesia induced by prostaglandin E2, in both females and males, was dependent on PKA and NO. In both sexes, inhibitors of mitogen-activated protein kinase/extracellular-signal related kinase kinase (MEK) inhibited epinephrine hyperalgesia. In gonadectomized females, the second messenger contributions to epinephrine hyperalgesia demonstrated the pattern seen in males. Administration of oestrogen to gonadectomized females fully reconstituted the phenotype of the normal female. These data demonstrate gender differences in PKCepsilon, PKA and NO signalling in epinephrine-induced hyperalgesia which are oestrogen dependent and appear to be exerted at the level of the beta-adrenergic receptor or the G-protein to which it is coupled.
authors.affiliation: Departments of Medicine and Oral and Maxillofacial Surgery, Division of Neuroscience and Biomedical Sciences Program, NIH Pain Center, University of California at San, Francisco, San Francisco, CA 94143-0440, USA.
authors.forename: O A
authors.initials: OA
authors.lastname: Dina
authors.forename: K O
authors.initials: KO
authors.lastname: Aley
authors.forename: W
authors.initials: W
authors.lastname: Isenberg
authors.forename: R O
authors.initials: RO
authors.lastname: Messing
authors.forename: J D
authors.initials: JD
authors.lastname: Levine
mesh_terms: D000322:Adrenergic Agonists / Q000494:pharmacology; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D036341:Intercellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D048369:MAP Kinase Kinase 1; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020929:Mitogen-Activated Protein Kinase Kinases / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism*; D010146:Pain / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D010455:Peptides / Q000494:pharmacology; D011493:Protein Kinase C / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D051744:Protein Kinase C-epsilon; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D000322:Adrenergic Agonists; D004791:Enzyme Inhibitors; D012739:Gonadal Steroid Hormones; D036341:Intercellular Signaling Peptides and Proteins; D007527:Isoenzymes; D010455:Peptides; C085074:Walsh peptide; D019323:omega-N-Methylarginine; D004958:Estradiol; D019001:Nitric Oxide Synthase; C497256:Prkce protein, mouse; C497257:Prkce protein, rat; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon; D048369:MAP Kinase Kinase 1; C482127:Map2k1 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases; D015232:Dinoprostone