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| NEURAL MECHANISMS OF GENITAL STIMULATION-PRODUCED PAIN BLOCKAGE IN FEMALES B.R. Komisaruk1, B. Whipple2, C.A. Gerdes3, S. Chinapen3, G.R. Sansone1, J.R. Bianca1, R.T. O’Bannon III3, M. Caba4 and C. Beyer5. 1Department of Psychology, 2College of Nursing, 3Program in Molecular and Behavioral Neuroscience, Rutgers -The State University of New Jersey, Newark, New Jersey 4Dpto. de Biologia, Univ. Autonoma. Veracruzana, Mexico, and Centro de Investigacion en Reproduccion Animal. CIRA. Universidad de Tlaxcala, Tlaxcala, Mexico Unique to females is the reproductive tract mechanostimulation that occurs during coitus, pregnancy and parturition. The sensory stimulation produces significant and robust analgesia during coital intromissions and ejaculation in rats, the females show a marked, transient (approx. 10 sec) elevation in pain threshold. Deafferentation of the vagina and cervix does not interrupt coitus, but it attenuates the analgesia. The magnitude of the females analgesia during the male's ejaculatory intromissions is equivalent to more than 15 mg/kg morphine sulfate. Vaginocervical mechanostimulation (VS) produces analgesia rather than anesthesia on the basis that: a) VS differentially blocks responses of single neurons in the somatosensory thalamus to noxious (e.g. foot pinch), but not innocuous (e.g. tactile) stimulation in rats, and b) vaginal and cervical self-stimulation in women markedly elevates pain thresholds but not tactile thresholds (both measured on the hands). If the vaginal self-stimulation is applied in a manner that the women report as feeling pleasurable or producing orgasm, the magnitude of induced analgesia is greater than if constant vaginal pressure is maintained. Pain thresholds are elevated during emergence of individual fetuses in rats during parturition, and during labor in women. Bilateral transection of the pelvic and hypogastric nerves, the combined sensory fields of which include the vagina, cervix and uterus, attenuates the analgesia of mating and pregnancy, and other behavioral, autonomic and neuroendocrine effects of VS. The sensory field of the pelvic nerve includes the rectum, mechanical stimulation of which produces a significant, but weaker analgesia in rats, not only in females, but also in males. Recently, we have reported analgesia to vaginal and cervical self-stimulation in women diagnosed with "complete" spinal cord injury at T-10 and higher, which is above the known level of entry into the spinal cord of both these nerves. We hypothesized a genital sensory role for vagus nerves to account for this unexpected finding. Supporting evidence was that brain mediated responses to VS (measured as pain thresholds and pupil dilatation) were reduced but not abolished by pelvic-hypogastric nerve transection bilaterally, or by surgical total transection of the spinal cord at T-7, and subsequent bilateral vagotomy abolished these responses. As further supporting evidence, on the basis of preliminary findings based on P.E.T. M.R.I. methodology in women with complete spinal cord injury above T-10, the region of the medulla oblongata to which the vagal afferents project (Nucleus of the Solitary Tract) is activated during cervical self-stimulation. These findings suggest that the vagus nerves provide a spinal cord bypass pathway mediating genital stimulation-produced analgesia. This is consistent with studies by others that vagal electrical stimulation can produce analgesia. It is likely that VS is a natural endogenous activator of the well-characterized lower brainstem-spinopetal analgesia-producing system. That is, VS significantly elevates serotonin, norepinephrine and glycine release into spinal cord superfusates, and intrathecal administration of the corresponding receptor antagonists attenuates VS-produced analgesia. In addition, VS-produced analgesia is attenuated by transection of the dorsolateral funiculus and by intrathecal administration of naloxone and GABA antagonists. VS blocks footshock-induced substance P release into spinal cord superfusates indicating that a major component of the analgesia is based on nociceptive primary afferent inhibition. VIP (Vasoactive Intestinal Peptide, containing 28 amino acids), a primary afferent peptide of the pelvic nerve, may play a role in initiating VS- produced analgesia. VIP is released into spinal cord superfusates in response to VS, and analgesia is produced by the intrathecal administration of VIP 1-28 and the 11-28, but not the 1-10, fragment. Neonatal capsaicin treatment blocks and even reverses VS-produced analgesia, and estrogen priming potentiates VS-produced analgesia. The occurrence of not only analgesia, but also pain syndromes (e.g. dyspareunia) in response to mechanostimulation of the reproductive tract probably depends on the balance and interaction among these multiple neural pathways and transmitter systems.
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