Ikeura Tsukasa, Kataoka Yosky, Wakabayashi Taketoshi, Mori Tetsuji, Takamori Yasuharu, Takamido Shoichiroh, Okazaki Kazuichi, Yamada Hisao
Department of Anatomy and Cell Science, Kansai Medical University, Fumizonocho 10-15, Moriguchi City, Osaka 570-8506, Japan.
Med Mol Morphol. 2007 Sep;40(3):141-9. doi: 10.1007/s00795-007-0374-7. Epub 2007 Sep 18.
Increase in the number of intrapancreatic sensory nerve fibers has been implicated in the generation of pain in chronic pancreatitis. Because some sensory neurotransmitters (e.g., substance P) are known to have proinflammatory effects, we hypothesized that denervation of intrapancreatic nerves might influence not only pain generation but also inflammation. Neonatal Lewis rats were injected with capsaicin (50 mg/kg or 0 mg/kg), a neurotoxin, to induce denervation of primary sensory neurons. When rats reached 170-190 g body weight, experimental pancreatitis was induced by a single administration of dibutyltin dichloride (7 mg/mg). The severity of pancreatitis was evaluated in both groups in the acute phase (at 3 and 7 days) and chronic phase (at 28 days). At day 7, the sensory denervation induced by neonatal capsaicin administration inhibited pancreatic inflammation on both histological (determination of interstitial edema, expansion of interlobular septa and intercellular spaces, and inflammatory cell infiltration) and biochemical (intrapancreatic myeloperoxidase activity) evaluation. Furthermore, at day 28, glandular atrophy, pseudotubular complexes, and rate of fibrosis were each significantly lower in the capsaicin-pretreated group than in the vehicle-pretreated group. Our findings provide in vivo evidence that primary sensory neurons play important roles in both acute pancreatitis and chronic pancreatic inflammation with fibrosis.
胰腺内感觉神经纤维数量的增加与慢性胰腺炎疼痛的产生有关。由于已知一些感觉神经递质（如P物质）具有促炎作用，我们推测胰腺内神经去神经支配可能不仅影响疼痛的产生，还会影响炎症。对新生的Lewis大鼠注射辣椒素（50毫克/千克或0毫克/千克），一种神经毒素，以诱导初级感觉神经元去神经支配。当大鼠体重达到170 - 190克时，通过单次给予二氯化二丁基锡（7毫克/毫克）诱导实验性胰腺炎。在急性期（3天和7天）和慢性期（28天）对两组胰腺炎的严重程度进行评估。在第7天，新生期给予辣椒素诱导的感觉去神经支配在组织学（间质水肿、小叶间隔和细胞间隙扩张以及炎性细胞浸润的测定）和生化（胰腺内髓过氧化物酶活性）评估中均抑制了胰腺炎症。此外，在第28天，辣椒素预处理组的腺体萎缩、假管状复合体和纤维化率均显著低于载体预处理组。我们的研究结果提供了体内证据，表明初级感觉神经元在急性胰腺炎和伴有纤维化的慢性胰腺炎症中均起重要作用。
