Lindsay T H, Halvorson K G, Peters C M, Ghilardi J R, Kuskowski M A, Wong G Y, Mantyh P W
Neurosystems Center and Department of Diagnostic and Biological Sciences, University of Minnesota, and Research Service, Veterans Affairs Medical Center, Minneapolis, MN 55455, USA.
Neuroscience. 2006;137(4):1417-26. doi: 10.1016/j.neuroscience.2005.10.055. Epub 2006 Jan 4.
Pain from pancreatitis or pancreatic cancer can be both chronic and severe although little is known about the mechanisms that generate and maintain this pain. To define the peripheral sensory and sympathetic fibers involved in transmitting and modulating pancreatic pain, immunohistochemistry and confocal microscopy were used to examine the sensory and sympathetic innervation of the head, body and tail of the normal mouse pancreas. Myelinated sensory fibers were labeled with an antibody raised against 200 kD neurofilament H (clone RT97), thinly myelinated and unmyelinated peptidergic sensory fibers were labeled with antibodies raised against calcitonin gene-related peptide (CGRP) and post-ganglionic sympathetic fibers were labeled with an antibody raised against tyrosine hydroxylase (TH). RT97, CGRP, and TH immunoreactive fibers were present in parenchyma of the head, body and tail of the pancreas with the relative density of both RT97 and CGRP expressing fibers being head>body>tail, whereas for TH, a relatively even distribution was observed. In all three regions of the pancreas, RT97 fibers were associated mainly with large blood vessels, the CGRP fibers were associated with the large- and medium-sized blood vessels and the TH were associated with the large- and medium-sized blood vessels as well as capillaries. In addition to this extensive set of sensory and sympathetic nerve fibers that terminate in the pancreas, there were large bundles of en passant nerve fibers in the dorsal region of the pancreas that expressed RT97 or CGRP and were associated with the superior mesenteric plexus. These data suggest the pancreas receives a significant sensory and sympathetic innervation. Understanding the factors and disease states that sensitize and/or directly excite the nerve fibers that terminate in the pancreas as well as those that are en passant may aid in the development of therapies that more effectively modulate the pain that frequently accompanies diseases of the pancreas, such as pancreatitis and pancreatic cancer.
胰腺炎或胰腺癌引起的疼痛可能既慢性又严重，尽管对于产生和维持这种疼痛的机制知之甚少。为了确定参与传递和调节胰腺疼痛的外周感觉神经纤维和交感神经纤维，采用免疫组织化学和共聚焦显微镜检查正常小鼠胰腺头部、体部和尾部的感觉神经和交感神经支配。有髓感觉神经纤维用抗200 kD神经丝H（克隆RT97）的抗体标记，薄髓和无髓肽能感觉神经纤维用抗降钙素基因相关肽（CGRP）的抗体标记，节后交感神经纤维用抗酪氨酸羟化酶（TH）的抗体标记。RT97、CGRP和TH免疫反应性纤维存在于胰腺头部、体部和尾部的实质中，表达RT97和CGRP的纤维相对密度为头部>体部>尾部，而对于TH，观察到相对均匀的分布。在胰腺的所有三个区域，RT97纤维主要与大血管相关，CGRP纤维与大中型血管相关，TH与大中型血管以及毛细血管相关。除了终止于胰腺的这一组广泛的感觉和交感神经纤维外，在胰腺背侧区域有大量的过路神经纤维束，它们表达RT97或CGRP，并与肠系膜上丛相关。这些数据表明胰腺接受大量的感觉和交感神经支配。了解使终止于胰腺的神经纤维以及过路神经纤维敏感化和/或直接兴奋的因素和疾病状态，可能有助于开发更有效地调节胰腺疾病（如胰腺炎和胰腺癌）常见疼痛的治疗方法。
