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，甚至对吗啡也有抵抗力。我们以前的研究已经确定，疼痛的癌症患者涉及盆腔内脏器官是缓解神经外科病变局限于脊髓背柱中线。我们确定，从胰腺的感觉输入主要传输到更高的大脑感觉处理中心作为中线组件的突触后背柱通路使用解剖，电生理和行为的方法。在我们的实验室最近，我们已经开发了一个模型的持续内脏疼痛的刘易斯近交系大鼠，类似于人类胰腺炎的血液值和组织学。该项目的目的是研究胰腺疼痛信号到达高级大脑中心的神经元通路，以及该通路的敏化如何导致持续性疼痛状态。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。 设计了以下假设和具体目标，以提高我们对慢性内脏疼痛处理的理解，从而实现改善治疗的长期目标： 假设：由发炎的胰腺产生的伤害性信息在脊髓中传递，通过内侧上行通路传递到更高的中枢，并在位于内侧的脑结构中产生中枢致敏。 具体目标1是确定持续性胰腺炎中激活的伤害性通路。具体目标2是在刘易斯近交系大鼠的持续性胰腺炎模型中减少维持中枢敏化的内脏伤害感受通路的激活。 预期的长期结果是，有关内脏伤害性通路的信息将有助于未来确定这些涉及胰腺的疼痛性疾病的治疗靶点。

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.