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

• Published in: Brain research bulletin Vol. 54; no. 2; pp. 213 - 218
• Main Authors: Boyle, Theodore J, Masuda, Takeshi, Cunningham, S.Tiffany
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 15-01-2001; Elsevier Science
• Subjects: Analgesics - pharmacology; Animals; Antinociception; Biological and medical sciences; Cervix Uteri - drug effects; Cervix Uteri - physiology; Dose-Response Relationship, Drug; Exploratory Behavior - drug effects; Exploratory Behavior - physiology; Female; Fundamental and applied biological sciences. Psychology; Mechanostimulation; Opiates; Opioid receptors (type ^K); Ovariectomy; Pain Threshold - drug effects; Pain Threshold - physiology; Physical Stimulation; Pyrrolidines - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Opioid, kappa - agonists; Receptors, Opioid, kappa - physiology; Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors; spiradoline; Tail flick latency; Vagina - drug effects; Vagina - physiology; Vertebrates: nervous system and sense organs; κ-Receptor; Mechanostimulation; Opiates; Antinociception; Tail flick latency; κ-Receptor; Nociception; Noxious stimulus; Agonist; Rat; Rodentia; κ Opioid receptor; Uterine cervix; Analgesia; Vertebrata; Mammalia; Spiradoline; Female genital system; Mechanical stimulus
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/S0361-9230(00)00453-6

Previous research has demonstrated increased pain threshold during copulation, gestation, and parturition in animals. In the laboratory, mechanostimulation of the vaginocervical region in many animals, as well as humans, can increase responsiveness to noxious but not to innocuous stimuli. This increased pain inhibition to vaginocervical stimulation, which mimics natural parturition, is mediated by spinal and supraspinal neuropeptides, including the opiates. The present research was designed to ascertain the possible effects of a kappa opioid agonist on vaginocervical-stimulated analgesia in rats. Initially, the novel kappa-selective agonist, spiradoline mesylate (U62,066E; 0, 0.1, 1.0, 10.0 mg/kg, i.p.), was injected intraperitoneally and general behavioral arousal in an open field apparatus was recorded. Results from this experiment indicate that stimulation with the kappa-selective drug caused significant decreases in behavioral activity at the high dose as compared to saline and the medium and low doses. Next, the effects of U62,066E (0, 0.1, 1.0, 10.0 mg/kg, i.p.) on the analgesia associated with vaginocervical stimulation were determined in a tail flick apparatus. The kappa drug significantly increased antinociceptive thresholds prior to and during vaginocervical 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-produced analgesia. Results are discussed in terms of the potential of nonaddictive kappa-selective opioid compounds being utilized in reproductive pain.