Gender and gonadal hormone effects on vagal modulation of tonic nociception

We studied the influence of gender and gonadal hormones on modulation of to nic nociception exerted by vagal activity. In male rats, subdiaphragmatic v agotomy resulted in significantly reduced nociceptive behavior during phase 2 of the formalin test. Whereas gonadectomy alone had no effect, it comple tely eliminated the suppressive effect of subdiaphragmatic vagotomy; howeve r, sex hormone replacement with either testosterone or dihydrotestosterone did not restore the ability of subdiaphragmatic vagotomy to suppress nocice ptive behavior. These results suggest that, in males, a gonad-dependent but androgenic gonadal hormone-independent mechanism contributes to pronocicep tive effects of vagal afferent activity. Although neither gonadectomy nor s ubdiaphragmatic vagotomy alone affected the response to formalin in females , gonadectomy plus vagotomy resulted in significantly reduced nociceptive b ehavior during phase 2. Reconstitution with 17 beta -estradiol implants in gonadectomized females not only prevented suppression of nociceptive behavi or seen with gonadectomy plus vagotomy, but also led to increased nocicepti ve behavior in the interphase between phases 1 and 2. However, placement of 17 beta -estradiol implants in gonad-intact females had no effect on forma lin-induced nociceptive behavior. The finding that estrogen produced an inc rease in nociceptive behavior in gonadectomized female rats after vagotomy but not in normal female rats (with intact gonads and subdiaphragmatic vagu s) suggests that the interaction between estrogen and nociceptive afferent activity is suppressed by vagal function. In conclusion, a nonandrogenic ac tion of testicular function in male rats and estrogen in females seems to i nfluence the effect of vagal activity on formalin-induced nociceptive behav ior.