UTERINE PAIN--MECHANISMS AND MODULATION

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DESCRIPTION: The long range objective of this research is to elucidate the pathophysiological mechanisms of pelvic pain in order to develop better strategies for alleviating pelvic pain syndromes in female and male patients. Chronic non-malignant and malignant pelvic pain syndromes are a major challenge to the clinician, and treatment strategies, including medical and surgical approaches, are often unsuccessful. The neuroanatomical and neurophysiological mechanisms underlying pelvic pain are poorly understood. The use of animal models is a necessary step in understanding the underlying neurophysiological and neuropharmacological mechanisms of pelvic pain. Our goals in the present studies are to develop an animal model of uterine pain using the rat, (1) to obtain detailed information about the spinal pathways that process nociceptive afferent input from the uterus, (2) to assess the effects of peripheral opioid application on the spinal processing of nociceptive input from the uterus, (3) to determine the influence of the estrous cycle on the spinal cord processing of noxious uterine stimulation and its pharmacological manipulation. Specific aim 1 is to characterize the behavioral manifestations of uterine pain induced by noxious distension, inflammation or ischemia. Specific aim 2 is to identify the spinal segments and laminae within these segments which process nociceptive afferent input from the uterus. These data, important in themselves, will also provide the anatomical basis for part of the pharmacological studies. Specific aim 3 is to examine the neurophysiological characteristics of dorsal horn neurons that respond to noxious uterine stimulation. The understanding of these characteristics will be the basis for future pharmacological interventions to alleviate pain from the uterus. Specific aim 4 is to answer the question, what are the peripheral effects of opioids on the spinal cord processing of noxious uterine stimulation? Recent, exogenous opioid agonists have been shown to have analgesic effects when administered in the vicinity of peripheral nerve terminals. This has been demonstrated in animal models as well as in patients with somatic pain; however, no data are available regarding uterine pain. These studies should fundamental new information concerning the neuroanatomical and neurophysiological mechanisms of uterine pain. They are the first studies attempting to examine whether peripherally applied opioids modulate the processing of uterine pain. The results of these experiments may rapidly contribute to the development of new pharmacological approaches to treat uterine pain syndromes.