analgesic effect of 17β-estradiol on nucleus paragigantocellularis lateralis of male rats mediated via gabaa receptors

Introduction: beside its autonomic functions, the nucleus paragigantocellularis lateralis (lpgi) is involved in the descending pain modulation. 17β-estradiol is a neuroactive steroid found in several brain areas such as lpgi. intra-lpgi microinjection of 17β-estradiol can elicit the analgesic responses. 17β-estradiol modulates nociception by binding to estrogenic receptors as well as allosteric interaction with other membrane-bound receptors like gabaa receptors. this study aimed to examine the role of gabaa receptors in the pain modulating effect of intra-lpgi injection of 17β-estradiol. methods: to study the antinociceptive effects of 17β-estradiol, cannulation into the lpgi nucleus of male wistar rats was performed. about 500 nl of drug was administered 15 minutes prior to formalin injection (50 μl of 4%). then, formalin-induced flexing and licking behaviors were recorded for 60 minutes. for evaluating the role of gabaa receptors in the estradiol-induced pain modulation, 17β-estradiol was administered into the lpgi nucleus 15 minutes after the injection of 25 ng/μl bicuculline (the gabaa receptor antagonist). then, the formalin-induced responses were recorded. results: the results of the current study showed that intra-lpgi injection of 17β-estradiol decreased the flexing duration in both phases of formalin test (p<0.001); but it only attenuated the second phase of licking behavior (p<0.001). 17β-estradiol attenuated the second phase of formalin test of both behaviors (p<0.001). bicuculline prevented the antinociceptive effect of intra-lpgi 17β-estradiol in both first and second phases of formalin-induced responses (p<0.001). conclusion: according to the results of this study, the analgesic effect of intra-lpgi 17β-estradiol on the formalin-induced inflammatory pain might be mediated via gabaa receptors.