Effects of a kappa agonist, spiradoline mesylate (U62,066E), on activationand vaginocervical-stimulation produced analgesia in rats

Previous research has demonstrated increased pain threshold during copulati on, gestation, and parturition in animals. In the laboratory, mechanostimul ation of the vaginocervical region in many animals, as well as humans. can increase responsiveness to noxious but not to innocuous stimuli. This incre ased pain inhibition to vaginocervical stimulation, which mimics natural pa rturition, is mediated by spinal and supraspinal neuropeptides, including t he opiates. The present research was designed to ascertain the possible eff ects of a kappa opioid agonist on vaginocervical-stimulated analgesia in ra ts. Initially. the novel kappa-selective agonist, spiradoline mesylate (Ug2 ,066E; 0, 0.1, 1.0, 10.0 mg/kg, i.p.), was injected intraperitoneally and g eneral behavioral arousal in an open field apparatus was recorded. Results from this experiment indicate that stimulation with the kappa-selective dru g caused significant decreases in behavioral activity at the high dose as c ompared to saline and the medium and low doses. Next, the effects of U62,06 6E (0, 0.1, 1.0, 10.0 mg/kg, i.p.) on the analgesia associated with vaginoc ervical stimulation were determined in a tail flick apparatus. The kappa dr ug significantly increased antinociceptive thresholds prior to and during v aginocervical stimulation at the 0.1 and 1.0 mg/kg doses. By contrast, the high dose (10.0 mg/kg) of U62,066E decreased vaginocervical stimulation-pro duced analgesia. Results are discussed in terms of the potential of nonaddi ctive kappa-selective opioid compounds being utilized in reproductive pain. (C) 2001 Elsevier Science Inc.