The antinociceptive effect of 17β-estradiol in the paragigantocellularis lateralis of male rats is mediated by estrogenic receptors

17β-Estradiol is a neuroactive steroid and its pain modulatory role has been well studied previously. 17β-Estradiol modulates nociception by binding to its receptors and also by allosteric interaction with other membrane - bound receptors such as glutamate and GABAA receptors. Paragigantocellularis lateralis (LPGi) is also involved in pain modulation and perception, in addition to its well-known autonomic functions such as regulation of circulation. In order to study the effect of intra-LPGi injection of 17β-estradiol on both acute and persistent pain, 50 μl of 4% formalin was injected into the male rats’ hind paw, then fo rmalin-induced paw jerking behaviour was recorded for 60 min. The results of this study indicated that intra-LPGi injection of 17β-estradiol attenuated the second phase, but not the acute phase of formalin induced pain (P< 0.001). The estrogen receptor antagonist (ICI182,780) counteracted 17β-estradiol’s effect, but could not reverse the antinociceptive effect of 17β -estradiol to its basic level. It may be concluded that a part of the analgesic effect of 17β-estradiol in formalin induced inflammatory pain is mediated by intracellular estrogen receptors; the other part of this effect is possibly mediated through allosteric interactions with other membrane-bound receptors such as glutamate and GABAA receptors.