Recent advancements in the pathogenesis of pain in chronic pancreatitis: the argument continues

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.