Wick Elizabeth C, Pikios Stella, Grady Eileen F, Kirkwood Kimberly S
Department of Surgery, University of California, San Francisco, USA.
Surgery. 2006 Feb;139(2):197-201. doi: 10.1016/j.surg.2005.08.024.
The mechanism by which pancreatitis causes pain is unknown. The neuropeptide calcitonin gene-related peptide (CGRP) is released after sensory nerve activation and promotes nociceptive signaling in models of visceral pain. We hypothesized that acute pancreatitis leads to the activation of pancreatic sensory neurons that release CGRP in the dorsal horn of the spinal cord. This signal is ultimately transmitted to the brain, and pain is sensed.
To induce pancreatitis, rats were injected with l-arginine (500 mg/kg) intraperitoneally or saline (control). Pancreatitis was confirmed by measuring serum amylase and evaluating pancreatic histology. Activation of nociceptive pathways was evaluated by counting Fos-like immunoreactive nuclei (FLI) in the dorsal horn of the spinal cord at T3-L1. Some animals received the CGRP antagonist CGRP(8-37) (50 microg intrathecally) 2 hours before perfusion. Animals were compared using a 2-tailed t test.
l-Arginine treatment induced acute necrotizing pancreatitis in the rat at 24 hours. l-Arginine (24 hours) increased FLI in the dorsal horn of the spinal cord, with a peak effect at L1. Intrathecal administration of CGRP(8-37) significantly decreased the number of FLI nuclei in the dorsal horn of the spinal cord in T11-L1.
Nociception in the l-arginine model of acute pancreatitis is partially mediated by the release of CGRP in the dorsal horn of the spinal cord. Antagonism of CGRP or its receptors may be useful in treating pain from acute pancreatitis.
胰腺炎引发疼痛的机制尚不清楚。神经肽降钙素基因相关肽（CGRP）在感觉神经激活后释放，并在内脏痛模型中促进伤害性信号传导。我们推测急性胰腺炎会导致胰腺感觉神经元激活，这些神经元在脊髓背角释放CGRP。该信号最终传递至大脑，从而产生疼痛感。
为诱导胰腺炎，给大鼠腹腔注射L-精氨酸（500mg/kg）或生理盐水（对照）。通过测量血清淀粉酶和评估胰腺组织学来确认胰腺炎。通过计数T3-L1脊髓背角中Fos样免疫反应性细胞核（FLI）来评估伤害性通路的激活情况。一些动物在灌注前2小时接受鞘内注射CGRP拮抗剂CGRP（8-37）（50μg）。使用双侧t检验对动物进行比较。
L-精氨酸处理在24小时时诱导大鼠发生急性坏死性胰腺炎。L-精氨酸（24小时）增加了脊髓背角中的FLI，在L1处达到峰值效应。鞘内注射CGRP（8-37）显著减少了T11-L1脊髓背角中FLI细胞核的数量。
急性胰腺炎L-精氨酸模型中的伤害感受部分由脊髓背角中CGRP的释放介导。CGRP或其受体的拮抗作用可能有助于治疗急性胰腺炎引起的疼痛。
