NEUROGENIC AMPLIFICATION OF PANCREATITIS PAIN

内脏疼痛是非常值得关注的，因为它构成了很大一部分的疼痛治疗的医学界。疼痛是胰腺或胰腺癌患者的主要主诉。这种疼痛可能很严重且难以治愈，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。在大鼠中，我们确定来自结肠的感觉输入主要作为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。这提出了一个主要内脏疼痛途径的可能性在背柱，我们将考虑作为一个整体的假设。我们建议进一步研究这一先前未被认识到的内脏疼痛途径，该途径与胰腺输入从胸椎水平传递有关。我们的初步数据支持以下关于胰腺伤害性信息传递的假设：来自胰腺的伤害性信息被传递到位于脊髓内侧的细胞。这些细胞将它们的轴突沿细筋束和楔形筋束之间的一条先前未描述的通路向上传递，支配髓质背束核的边缘。这些信息随后被传递到丘脑。该研究的目的之一是确定大鼠胰腺传入纤维的电和化学刺激引起的有害信息传递的中枢神经元通路。通往感觉处理中心的路径将被绘制出来。一个目的是评估通路中断作为废除胰腺伤害性传递的手段。另一个目的是研究谷氨酸受体拮抗剂对胰腺炎模型的药理学干预。该项目采用多学科方法，包括电生理学，行为学和解剖学方法，为理解这些涉及胰腺的破坏性疼痛状况的伤害性加工提供了基础信息。

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.