Pathogenesis of Pain in Chronic Pancreatitis

The pathophysiology of pain in chronic pancreatitis (CP) is incompletely understood. Several hypotheses have been advanced, including pancreatic and extrapancreatic causes. The existence of different hypotheses to explain the genesis of pain in CP also reflects the different therapeutic approaches to pain in these patients. Increased intraductal pressure as a result of single or multiple strictures and/or calculi is believed to be a common cause of pain in CP patients with a dilated main pancreatic duct. Other suggested causes include pancreatic fibrosis, interstitial hypertension and pancreatic ischemia. Additionally, extrapancreatic causes like duodenal and common bile duct stenosis with scarring due to pancreatic inflammation are suggested as factors causing pain in CP. The 'neurogenic inflammation' hypothesis is a fascinating theory which is supported by different studies. Immunohistological reports have shown that the amount of neurotransmitters, such as substance P and its receptor, calcitonin gene-related peptide and other neurotransmitters, are increased in afferent pancreatic nerves and a correlation between pain and immune cell infiltration of the nerves has been reported in CP. In this review we will discuss the different pain hypotheses and will present the perspective that neuroimmune interaction is an important factor for pain generation in CP.