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Introduction: Estradiol is a neuroactive steroid, which is found in several brain areas such as locus coeruleus (LC). Estradiol modulates nociception by binding to its receptors and also by allosteric interaction with other membranebound receptors like glutamate and GABAA receptors. LC is involved in noradrenergic descending pain modulation. Methods: In order to study the effect of 17β-estradiol on both acute and persistent pain modulation and its mechanisms, formalin was injected into the hind paw of male rats. Formalin-induced responses including licking and flexing duration and paw jerking frequency were recorded for 60 min after injection of 50 μl of 2% formalin. Also, the expression of α2 and γ1 subunits of GABAA receptor genes were examined by RT-PCR technique. Results: The results of the current study showed that intra-locus coeruleus injection of 17β-estradiol attenuated the second phase, but not the acute phase of formalin induced pain (P< 0.05). GABAA receptor antagonist (bicuculline) reversed the antinociceptive effect of 17β-estradiol, but the expression level of α2 and γ1 subunits of GABAA receptor genes were not significantly changed. Conclusion: It may be concluded that the analgesic effect of 17β-estradiol in formalin induced inflammatory pain is possibly mediated through the interaction with membrane-bound GABAA receptors, however this effect is not exerted at the gene expression level.

Keywords: locus coeruleus nucleus, 17-β-estradiol, bicuculline, pain modulation, rat

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