The sensory mechanisms underlying visceral pain are poorly understood. One consequence of visceral disease is pain referred to somatic tissue. In patients with colonic disorders, pain is referred to pelvic and abdominal dermatomes. Based on our understanding of referred pain and the innervation of the colon it appears that inflammation alters colonic sensory processing in the spinal cord. We will test this hypothesis in a model of acute and colonic inflammatory pain in the rat. We will further test the hypothesis that alterations in descending modulation (inhibition, facilitation) contribute to the plasticity and that neonatal injury permanently alters the normal pattern of descending modulation contributing to visceral hypersensitivity. These hypotheses will be tested in the following specific aims: 1: Determine the contribution of the lumbosacral and will be tested in the following specific aims: 1: Determine the contribution of the lumbosacral and thoracolumbar spinal cord segments to spinal processing of acute and inflammatory colonic pain. Parallel methods measuring pseudoaffective reflexes (visceromotor reflex, vmr and pressor reflex, PR) and Fos expression in the spinal cord will be used to examine the role of the pelvic nerve-lumbosacral spinal cord circuitry and hypogastric/lumbar colonic nerve-thoracolumbar spinal cord circuitry in processing acute noxious CRD in the absence and presence of colonic inflammation; 2: Determine if descending inhibition can account for the inactivity in the thoracolumbar spinal cord to acute noxious CRD and if alterations in descending inhibition can account for the inactivity in the thoracolumbar spinal cord to acute noxious CRD and if alterations in descending modulation contribute to the observed plasticity following colonic inflammation. Intrathecal administration of NE/5-HT receptor antagonists and selective spinal (DLF) and brainstem lesions will be used to examine the role of descending inhibition in visceral sensory processing in the presence and absence of colonic inflammation; 3. Determine if neonatal injury (somatic or visceral) alters visceral sensory processing in the adult. We will determine if the pattern of descending modulation revealed by selective brainstem and spinal cord lesions demonstrated in Aim 2 has been altered and if these alterations care modality specific or affect sensory processing in the spinal cord in general.
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