Animal models for the study of uterine pain have focused on either distension or inflammatory protocols, although there appear to be significantly fewer studies in the current literature compared to, for example, the colon or bladder. Uterine inflammation in the anesthetized rat can be achieved by the introduction of 10% mustard oil into one uterine horn through an implanted catheter (97). A modification of this model enabled its behavioral characterization, and involved the tight ligation of one uterine horn followed by the injection of mustard oil into the lumen, with the rats subsequently allowed to recover (98). Observation of the rats over the following seven days revealed abnormal behavior similar to that reported for the ureteral calculosis model (among others) described above, in the majority (11 of 14) of rats. No sham-operated controls showed these behaviors. Muscle hypersensitivity of the lower back and flanks (a referred pain perhaps comparable to pelvic pain seen in patients) that remained after the extinction of abnormal behavior was recorded in two-thirds (six of nine) of animals studied with abnormal behavior following mustard oil instillation.
As with a number of the organ systems discussed in this chapter, distension is also used as a method to invoke uterine pain. This can be achieved by implanting, under anesthesia, a balloon (approximately 5 mm long and 1.5 mm wide) and its attached catheter into the right uterine horn of a rat. The catheter is then secured in place, and the end exteriorized (99). The balloon can be filled with water to various volumes, calibrated for each animal individually while under anesthesia. Berkley et al. used an operant response, the escape response to a noxious tail pinch, to assess the behavioral responses to uterine distensions, and found that, similar to the uterine inflammation model above, only about three-quarters (17 of 23) of the animals responded to distension (99). However, for these 17 animals, their probability of presenting an escape response increased with the distension volume. The authors point out that the magnitude of uterine distension required to elicit responses is beyond the range of any natural event, at least in nonpregnant or parturient animals; thus it is not clear how appropriate this model may be as a clinical correlate of uterine pain.
Endometriosis, while not exclusively an uterine phenomenon, is a common clinical disorder that is often accompanied by severe dysmenorrhea (painful menstruation), painful defecation, chronic pelvic pain, and dyspareunia (pain during sexual intercourse), and thus is relevant to this discussion. It is characterized by the growth of uterine tissue outside of the uterus and has been modeled in both the rat (100) and the mouse (101), although behavioral data is only currently available in the rat (102). One uterine horn is removed surgically from animals and placed in culture medium at 37°C, where it is cut into equal-sized fragments (three to six, depending upon species and laboratory), each of which is then sutured to a blood vessel in the mesentery of the small intestine, lower abdominal wall, ovary, or all three (note that autotransplants to the abdominal wall rarely produce cysts, and only small ones when they do). Following wound closure, the animal is allowed to recover. In all (five) rats that developed cysts resulting from this procedure, escape responses to vaginal distension were significantly increased postsurgery versus presurgery (102). This indication of the development of vaginal hypersensitivity was not seen in sham controls that received autotransplantation of fat, not uterine horn tissue.
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