The effect of intra-locus coeruleus injection of 17β-estradiol on inflammatory pain modulation in male rat

Abstract

Estradiol is a neuroactive steroid found in several brain areas such as locus coeruleus (LC). It modulates nociception by binding to its receptors and also by allosteric interaction with other membrane-bound receptors like glutamate and GABA A receptors. LC is involved in noradrenergic descending pain modulation. In order to study the effect of 17β-estradiol on both acute and persistent pain modulation and its mechanisms, formalin was injected into the male rat's hind paw. Formalin-induced responses including licking, flexing duration and paw jerking frequency were recorded for 60 min after injection of 50 μl of 2% formalin. 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). AMPA receptor antagonists CNQX had no effect on pain-modulatory effect of 17β-estradiol. Estrogen and GABA A receptor antagonists (ICI 182,780 and bicuculline, respectively) could not reverse the antinociceptive effect of 17β-estradiol. However, NMDA receptor antagonist APV significantly antagonized the analgesic effect of 17β-estradiol on flexing behaviour ( P < 0.05). It may be concluded that the analgesic effect of 17β-estradiol in formalin-induced inflammatory pain is mediated through interaction with membrane-bound receptors, probably the NMDA receptors.