Sex-differential modulation of visceral pain by brain derived neurotrophic factor (BDNF) in rats

In spite of the fact that brain derived neurotrophic factor (BDNF) has been reported to be implicated in the development of visceral pain, it remains to be determined whether the role of BDNF in pain is gender dependent. The present study investigated the effect of BDNF on visceral pain in different gender rats. A model for visceral pain was established by intraperitoneal (i.p.) injection of acetic acid (AA) into Sprague-Dawley rats: males, females and females with an ovariectomy (OVX). The pain behavior index was assessed by counting the number of abdominal contractions for 60min after i.p. injection of AA. Anti-BDNF antibody, or BDNF, was administered 1h before the AA injection to examine the role of BDNF in visceral pain. After the AA injection, the number of abdominal contraction was dramatically increased in all rats but females showed more severe pain behavior than males. The higher sensitivity to AA-induced nocifensive response was attenuated by OVX. Pretreatment with anti-BDNF antibody significantly exacerbated the nocifensive response in males but attenuated it in females. While exogenous BDNF administration did not alter AA injection-induced nocifensive response in females, BDNF pretreatment attenuated the nocifensive response in males but exacerbated it in females with OVX. The present study suggests there is a gender dichotomy in visceral pain induced by AA injection. In addition, the modulation of visceral pain by BDNF is also sex dependent, i.e., BDNF facilitates the visceral pain in female rats but displays an opposite effect in male rats. Our results may have important implications in the management of clinical pain.