Neurogeneic Amplification of Pancreatitis Pain

描述（由申请人提供）：许多胰腺炎或胰腺癌患者主诉腹痛，甚至对吗啡也有抗药性。我们之前的研究已经确定，通过神经外科病变限制在脊髓背柱中线，盆腔脏器癌患者的疼痛得到缓解。我们使用解剖学、电生理学和行为学方法确定，来自胰腺的感觉输入主要作为突触后背柱通路的中线组成部分传递到更高的大脑感觉处理中心。在我们的实验室里，我们最近开发了一种刘易斯近交系大鼠持续内脏疼痛的模型，在血液值和组织学上类似于人类胰腺炎。该项目的目的是研究胰腺疼痛信号到达大脑高级中枢的神经元通路，以及该通路的敏化如何导致持续的疼痛状态。采用多学科方法，包括行为、电生理和功能磁共振成像（fMRI）方法。

DESCRIPTION (provided by applicant): Many patients with pancreatitis or pancreatic cancer complain of abdominal pain that is 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. We determined that sensory input from the pancreas is primarily transmitted to higher brain sensory processing centers as a midline component of the postsynaptic dorsal column pathway using anatomical, electrophysiological and behavioral methods. In our laboratory recently we have developed a model of persistent visceral pain in Lewis inbred rats that resembles human pancreatitis in blood values and histology. The purpose of the proposed project is to study the neuronal pathway by which pain signals from the pancreas reach higher brain centers and how sensitization of this pathway can lead to persistent pain states. A multidisciplinary approach is used including behavioral, electrophysiological, and functional magnetic resonance imaging (fMRI) methods. The following hypothesis and specific aims were devised to improve our understanding of chronic visceral pain processing toward the long term goal of improved therapy: HYPOTHESIS: Nociceptive information arising from the inflamed pancreas is relayed in the spinal cord, transmitted through medially ascending pathways to higher centers, and produces central sensitization in medially located brain structures. Specific Aim 1 is to determine the nociceptive pathways activated in persistent pancreatitis. Specific Aim 2 is to reduce activation in the visceral nociceptive pathways maintaining central sensitization in a persistent pancreatitis model in Lewis inbred rats. The long-term outcome expected is that information about the visceral nociceptive pathway will contribute to future identification of therapeutic targets for these devastatingly painful conditions involving the pancreas.