NEUROGENIC AMPLIFICATION OF PANCREATITIS PAIN

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Visceral pain is of great concern since it constitutes a large part of the pain treated by the medical community. Pain is a major complaint in particular of patients with pancreatis or pancreatic cancer. The pain can be severe and intractable, resistant even to morphine. Our previous studies have determined that pain in patients with cancer involving the pelvic visceral organs is relieved by a neurosurgical lesion limited to the midline of the dorsal column of the spinal cord. In rats we determined that sensory input from the colon is primarily transmitted to higher brain sensory processing centers as a midline component of the dorsal column pathways. This raises the possibility of a major visceral pain pathway in the dorsal column which we will consider as an overall hypothesis. We propose further study of this previously unrecognized visceral pain pathway relevant to transmission of pancreatic inputs from thoracic levels. Our preliminary data support the following hypothesis for transmission of pancreatic nociceptive information: Nociceptive information from the pancreas is transmitted to cells located medially in the spinal cord. These cells send their axons up the dorsal columns in a previously undescribed pathway between the gracile and cuneate fasciculi to innervate the edges of the dorsal column nuclei in the medulla. The information is then relayed to the thalamus. One aim of the proposed studies will define the central neuronal pathway responsible for transmission of noxious information evoked by electrical and chemical stimulation of pancreatic afferent fibers in rats. The route of the pathway to sensory processing centers will be mapped. One aim will assess pathway disruption as a means of abrogating pancreatic nociceptive transmission. Another aim will examine pharmacological intervention with glutamate receptor antagonists in pancreatitis models. This project using a multidisciplinary approach including electrophysiological, behavioral and anatomical methods should provide information fundamental to the understanding of nociceptive processing in these devastatingly painful conditions involving the pancreas.