title: Activation of the trigeminal α2-adrenoceptor produces sex-specific, estrogen dependent thermal antinociception and antihyperalgesia using an operant pain assay in the rat.
abstract: Higher prevalence of several pain disorders in women and sexual dimorphism in G-protein coupled receptor-induced analgesia has been reported. We have previously shown that α2-adrenoceptor-induced antinociception is sex-specific and attenuated by estrogen in the female rat. However, this evidence was obtained using reflexive withdrawal-based nociceptive assays conducted on restrained animals that may not involve cerebral processing. Hence, we evaluated whether activation of the trigeminal α2-adrenoceptor produces sex-specific antinociceptive and antihyperalgesic effects in the orofacial region of the rat using a reward conflict-based operant paradigm in which animals must tolerate nociceptive thermal stimulation to be rewarded. Male and ovariectomized (OVX) Sprague-Dawley rats were implanted intracisternally with a PE10 cannula for drug injections. A group of OVX rats (OVX+E) was administered subcutaneously with estradiol 48h before the test. Effect of clonidine, an α2-adrenoceptor agonist, was determined on the operant pain assay using a fully automated Orofacial Pain Assessment Device. Number of spout licks, thermode contacts, and amount of reward intake were automatically recorded by the ANY-maze software. Using acute pain modeling, clonidine produced a dose-dependent increase in all three parameters in male and OVX groups, however, it was ineffective in the OVX+E group. Similarly, using inflammatory pain modeling, clonidine significantly increased these parameters in carrageenan-treated male and OVX groups but not in the OVX+E group. Thus, α2-adrenoceptor activation produces sex-specific antinociception and antihyperalgesia and estrogen attenuates these effects in female rats using an operant pain assay. These findings may help the discovery of effective analgesics for each sex.
authors: Department of Neuroscience and Pharmacology, Meharry Medical College, Nashville, TN 37208, United States. Electronic address: snag@mmc.edu.
authors: Subodh
authors: S
authors: Nag
authors: Department of Neuroscience and Pharmacology, Meharry Medical College, Nashville, TN 37208, United States.
authors: Sukhbir S
authors: SS
authors: Mokha
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006930:Hyperalgesia / Q000378:metabolism*; D008297:Male; D010052:Ovariectomy / Q000379:methods; D010146:Pain / Q000188:drug therapy / Q000378:metabolism*; D010147:Pain Measurement / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000502:physiology; D012727:Sex Characteristics; D013739:Testosterone / Q000494:pharmacology
chemical_list: D000700:Analgesics; D004967:Estrogens; D018341:Receptors, Adrenergic, alpha-2; D013739:Testosterone; D003000:Clonidine
keywords: Clonidine; Estrogen; Operant; Pain; Sex-differences; α(2)-Adrenoceptor