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. 17&beta;-Estradiol is a neuroactive steroid found in several brain areas such as LPGi. Intra-LPGi microinjection of 17&beta;-estradiol can elicit the analgesic responses. 17&beta;-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 17&beta;-estradiol. Methods: To study the antinociceptive effects of 17&beta;-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 &mu;L 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, 17&beta;-estradiol was administered into the LPGi nucleus 15 minutes after the injection of 25 ng/&mu;L 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 17&beta;-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). 17&beta;-estradiol attenuated the second phase of formalin test of both behaviors (P<0.001). Bicuculline prevented the antinociceptive effect of intra-LPGi 17&beta;-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 17&beta;-estradiol on the formalin-induced inflammatory pain might be mediated via GABAA receptors.&nbsp;