Winston John H, He Zhi-Jun, Shenoy Mohan, Xiao Shu-Yuan, Pasricha Pankaj Jay
Division of Gastroenterology and Hepatology, Department of Internal Medicine, The University of Texas Medical Branch, 4.106 McCullough Building, 301 University Boulevard, Galveston TX 77555-0764, USA.
Pain. 2005 Sep;117(1-2):214-22. doi: 10.1016/j.pain.2005.06.013.
The approach to the management of painful chronic pancreatitis has been empirical, primarily due to the lack of information about biological mechanisms producing pain. To facilitate research into pain mechanisms, our aim was to assess a rat model of chronic pancreatitis induced by pancreatic infusion of trinitrobenzene sulfonic acid as a model of painful pancreatitis. Nociception was assessed by measuring mechanical sensitivity of the abdomen and by recording the number of nocifensive behaviors in response to electrical stimulation of the pancreas. Expression of neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP) in the thoracic dorsal root ganglia receiving input from the pancreas and nerve growth factor (NGF) in the pancreas were measured. Rats with pancreatitis exhibited marked increase in sensitivity to mechanical probing of the abdomen and increased sensitivity to noxious electrical stimulation of the pancreas. There were significant increases in NGF protein in the pancreas and in expression of neuropeptides CGRP and SP in the sensory neurons from dorsal root ganglia receiving input from the pancreas. We have established quantitative measures of referred nociception and pancreatic hyperalgesia in a rat model of chronic pancreatitis that bears histological similarities to the human disease. This model has considerable construct, face and predictive validity for the human condition. It is of importance for the study of the pathogenesis of pain in this condition and can facilitate the development of new therapeutic options.
由于缺乏关于产生疼痛的生物学机制的信息，慢性疼痛性胰腺炎的管理方法一直是经验性的。为了促进对疼痛机制的研究，我们的目标是评估通过胰腺内注入三硝基苯磺酸诱导的慢性胰腺炎大鼠模型，作为疼痛性胰腺炎的模型。通过测量腹部的机械敏感性以及记录对胰腺电刺激的伤害性反应行为的数量来评估伤害感受。测量了接受来自胰腺输入的胸段背根神经节中神经肽降钙素基因相关肽（CGRP）和P物质（SP）的表达以及胰腺中神经生长因子（NGF）的表达。患有胰腺炎的大鼠对腹部的机械探测敏感性显著增加，对胰腺的有害电刺激敏感性增加。胰腺中NGF蛋白以及接受来自胰腺输入的背根神经节感觉神经元中神经肽CGRP和SP的表达均显著增加。我们已经在与人类疾病具有组织学相似性的慢性胰腺炎大鼠模型中建立了牵涉性痛觉过敏和胰腺痛觉过敏的定量测量方法。该模型对于人类情况具有相当的结构、表面和预测效度。它对于研究这种情况下疼痛的发病机制很重要，并且可以促进新治疗方法的开发。
