Pii: S0304-3959(99)00049-4

Response properties of peripheral afferent ®bers supplying the vagina and uterus of the rat vary with estrous stage (Robbins A, Berkley KJ, Sato Y. Estrous cycle variation of afferent ®bers supplying reproductive organs in the female rat. Brain Res 1992;596:353±356), suggesting that behavioral sensitivity to vaginal and uterine stimulation might similarly vary. To test this hypothesis, detection and escape responses of 12 rats to different volumes of distention of the vaginal canal or uterine horn (six rats each) were compared during each of the four estrous stages, proestrus (P), estrus (E), metestrus (M), and diestrus (D), using previously-published behavioral techniques (Berkley KJ, Wood E, Sco®eld SL, Little M. Behavioral responses to uterine or vaginal distention in the rat. Pain 1995;61:121±131). Estrous variations in vaginal or uterine tone (pressure-volume functions) were also measured in the same rats. Vaginal canal: escape response percentages increased signi®cantly as vaginal distention volume increased, but neither escape nor detection responses varied with estrous stage. Vaginal tone, however, was greater in P and E than in M and D, with the greatest tone in E and the least in D. When escape responses to different pressures were analyzed, it was found that escape response percentages to the same vaginal pressure were lower during P and E than during M and D. One outcome of these estrous in ̄uences would be that a vaginal stimulus of a given volume (such as an erect penis) would exert higher pressures during P and E (i.e. the penis would be held within the vaginal canal more ®rmly) than during M and D, but would be less likely during P and E to provoke escape responses. This modi®cation of nociceptive sensitivity has obvious reproductive advantages, because P and E constitute the rat's fertile period. Uterine horn: escape response percentages increased signi®cantly as uterine distention volume increased only during M and D, with no differences between them. Detection responses also occurred only during M and D. Similarly, uterine tone was signi®cantly greater in M and D than in P and E, with the greatest tone occurring during M and the least during P. Although these changes in uterine tone were opposite to those of the vaginal canal, escape response percentages to the same uterine pressures were, in a manner similar to vaginal pressures, lower during P and E than during M and D. The functional signi®cance of these variations for the uterus is unclear, but does suggest that, under pathophysiological conditions, stimulation of the uterine horn, as well as the vaginal canal, would be more likely to provoke escape behaviors in M and D than in P and E. A similar increased sensitivity in rats during M and D to noxious stimulation of other pelvic organs has been observed by others. This situation resembles that in women, for whom many visceral pain conditions are exacerbated during a comparable part of their ovarian cycle, i.e. perimenstrually. q 1999 International Association for the Study of Pain. Published by Elsevier Science B.V.