Role of sensory nerves in pancreatic secretion and caerulein-induced pancreatitis

Sensory nerves are implicated in gastroprotection and regulation of visceral circulation but their role in exocrine secretion and pancreatic circulation in intact pancreas and in acute pancreatitis has not been established. We investigated the role of sensory fibers in pancreatic secretion in vivo and amylase release from pancreatic slices (containing nerve fibers) or isolated pancreatic acini, and in caerulein-induced pancreatitis. In conscious rats, the stimulation of sensory nerves by low dose of capsaicin given intraduodenally (0.25-0.5 mg/kg) reduced basal pancreatic secretion, whereas dose of 1 mg/kg increased this secretion. Deactivation of sensory nerves by neurotoxic dose of capsaicin (100 mg/kg over 3 days s.c.) 10 days before tests failed to affect basal secretion but diminished the secretion induced by feeding or the diversion of pancreatic juice. In pancreatic slices, capsaicin (10(-10)-10(-6) M) increased enzyme secretion and this response was abolished by atropine (10(-6) M) or previous deactivation of sensory nerves. In pancreatic acini, capsaicin failed to affect basal and stimulated amylase secretion in response to caerulein or urecholine. In intact rats, stimulatory dose of capsaicin (0.5 mg/kg i.g.) caused about 32% increase of pancreatic blood flow and it was without any effect on the pancreatic DNA synthesis, weight, RNA, DNA and protein content. In contrast, neurotoxic dose of capsaicin caused a reduction (by 27%) in pancreatic blood flow followed by a significant decrease in RNA content and DNA synthesis in pancreatic tissue. Infusion of caerulein (10 g/kg-h) for 5 h produced acute edematous pancreatitis accompanied by over 60% decrease in DNA synthesis, nearly 50% inhibition of pancreatic blood flow, and a significant increase in pancreatic weight, protein content and plasma amylase concentration. Stimulatory dose of capsaicin attenuated the pancreatic tissue damage in caerulein induced pancreatitis, as manifested by a significant reversal of pancreatic blood flow and DNA synthesis decrease. Capsaicin induced inactivation of sensory nerves prior to pancreatitis caused an increase of all parameters of pancreatic damage; pancreatic blood flow dropped by 68%, DNA synthesis decreased by 70%; pancreatic weight, protein content and plasma amylase were also significantly enhanced. We conclude that sensory neurons are involved in the regulation of pancreatic secretion by an indirect mechanism and exhibit a beneficial effect on the pancreatic integrity, mainly due to improving the pancreatic blood flow.