title: The effect of intra-locus coeruleus injection of 17beta-estradiol on inflammatory pain modulation in male rat.
abstract: Estradiol is a neuroactive steroid found in several brain areas such as locus coeruleus (LC). It modulates nociception by binding to its receptors and also by allosteric interaction with other membrane-bound receptors like glutamate and GABA(A) receptors. LC is involved in noradrenergic descending pain modulation. In order to study the effect of 17beta-estradiol on both acute and persistent pain modulation and its mechanisms, formalin was injected into the male rat's hind paw. Formalin-induced responses including licking, flexing duration and paw jerking frequency were recorded for 60 min after injection of 50 microl of 2% formalin. The results of the current study showed that intra-locus coeruleus injection of 17beta-estradiol attenuated the second phase, but not the acute phase of formalin-induced pain (P<0.05). AMPA receptor antagonists CNQX had no effect on pain-modulatory effect of 17beta-estradiol. Estrogen and GABA(A) receptor antagonists (ICI 182,780 and bicuculline, respectively) could not reverse the antinociceptive effect of 17beta-estradiol. However, NMDA receptor antagonist APV significantly antagonized the analgesic effect of 17beta-estradiol on flexing behaviour (P<0.05). It may be concluded that the analgesic effect of 17beta-estradiol in formalin-induced inflammatory pain is mediated through interaction with membrane-bound receptors, probably the NMDA receptors.
authors.affiliation: Department of Physiology, Tarbiat Modares University, P.O. Box: 14115-116, Tehran, Iran.
authors.forename: Roghaieh
authors.initials: R
authors.lastname: Khakpay
authors.forename: Saeed
authors.initials: S
authors.lastname: Semnanian
authors.forename: Mohammad
authors.initials: M
authors.lastname: Javan
authors.forename: Mahyar
authors.initials: M
authors.lastname: Janahmadi
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004195:Disease Models, Animal; D004958:Estradiol / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005557:Formaldehyde; D000077267:Fulvestrant; D007249:Inflammation / Q000188:drug therapy*; D008125:Locus Coeruleus / Q000187:drug effects*; D008297:Male; D008845:Microinjections; D010146:Pain / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D004965:Estrogen Antagonists; D004967:Estrogens; D005557:Formaldehyde; D000077267:Fulvestrant; D004958:Estradiol; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine; D001640:Bicuculline