Navaneethan U, Venkataraman J
Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio 45219, USA.
Minerva Gastroenterol Dietol. 2010 Mar;56(1):55-63.
Chronic pancreatitis is a state of chronic inflammation characterized by progressive destruction of the pancreas. Pancreatic pain, a cardinal symptom in chronic pancreatitis patients has always been a subject of great interest and controversy. The precise mechanism of pain and its persistence in chronic pancreatitis patients remain unknown. Several pancreatic, neurogenic and central hypotheses have been proposed for the pathogenesis of pain. In patients with a dilated main pancreatic duct, increased intraductal pressure due to strictures/calculi, presence of interstitial hypertension, pancreatic ischemia and fibrosis and pseudocyst have been proposed to contribute to chronic pain. "Neurogenic" or "neuropathic" theory is based on the fact that patients with chronic pancreatitis have enlarged intrapancreatic nerves with microscopic damage to nerve sheaths (mediated by growth-associated protein 43 (GAP-43), that makes them more susceptible to mediators like brain derived neurotrophic factor, nerve growth factor and TrkA and artemin, the expression of which directly correlates with severity of pain frequency and intensity. The central theory proposes that reorganization of neurons in the insula may explain the chronic pain in these patients. However all these studies have been observational. Further studies are required in the future to characterize these immune response observed in the intrapancreatic neurons in chronic pancreatitis and the neuronal changes in the brain if we are to manage these patients with chronic pain and give them a better quality of life.
慢性胰腺炎是一种以胰腺进行性破坏为特征的慢性炎症状态。胰腺疼痛是慢性胰腺炎患者的主要症状，一直是备受关注和争议的话题。慢性胰腺炎患者疼痛的确切机制及其持续存在的原因仍不清楚。关于疼痛的发病机制，已经提出了几种胰腺、神经源性和中枢性假说。在主胰管扩张的患者中，有人提出由于狭窄/结石导致的导管内压力升高、间质高血压、胰腺缺血和纤维化以及假性囊肿是慢性疼痛的原因。“神经源性”或“神经性”理论基于这样一个事实，即慢性胰腺炎患者胰腺内神经增大，神经鞘有微观损伤（由生长相关蛋白43（GAP-43）介导），这使得它们更容易受到脑源性神经营养因子、神经生长因子和TrkA以及artemin等介质的影响，这些介质的表达与疼痛频率和强度的严重程度直接相关。中枢理论提出，岛叶神经元的重组可能解释了这些患者的慢性疼痛。然而，所有这些研究都是观察性的。如果我们要治疗这些慢性疼痛患者并提高他们的生活质量，未来需要进一步研究来明确慢性胰腺炎患者胰腺内神经元中观察到的这些免疫反应以及大脑中的神经元变化。
