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

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 GABAA 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 GABAA 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.

Research highlights▶ Intra-LC injection of 17β-estradiol is sufficient to produce moderate analgesia. ▶ ICI 182,780, bicuculline and CNQX could not completely block the antinociceptive effect of 17β-estradiol in the LC. ▶ APV antagonized the analgesic effect of 17β-estradiol in the LC. ▶ The antinociceptive effect of 17β-estradiol in the LC is mostly mediated by non-estrogen receptors. ▶ NMDA receptor seems to be involved in 17β.