NEUROGENIC AMPLIFICATION OF PANCREATITIS PAIN

内脏疼痛是非常令人担忧的，因为它构成了医学界治疗的疼痛的很大一部分。疼痛是胰腺炎或胰腺癌患者的主要主诉。疼痛可能是剧烈的和难以治愈的，甚至对吗啡也有抵抗力。我们以前的研究已经确定，累及盆腔内脏的癌症患者的疼痛可以通过局限于脊髓背柱中线的神经外科病变来缓解。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成分传递到更高级别的大脑感觉处理中心。这增加了背柱主要内脏痛通路的可能性，我们将把它作为一个整体假说来考虑。我们建议对这一先前未知的内脏疼痛通路进行进一步研究，该通路与胰腺从胸椎水平传入的传导有关。我们的初步数据支持以下关于胰腺伤害性信息传递的假说：来自胰腺的伤害性信息被传递到位于脊髓内侧的细胞。这些细胞在薄束和楔状束之间以一条先前未描述的途径将轴突向上发送到背柱，以神经支配延髓中背柱核的边缘。然后，这些信息被传递到丘脑。这项研究的目的之一将确定负责传递由电和化学刺激大鼠胰腺传入纤维引起的伤害性信息的中枢神经通路。通往感觉处理中心的路线将被绘制成地图。一个目标是评估通路中断作为消除胰腺伤害性信息传递的一种手段。另一个目的是检查谷氨酸受体拮抗剂对胰腺炎模型的药物干预。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，应该为理解涉及胰腺的这些毁灭性疼痛条件下的伤害性处理提供基本信息。

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.