ROLE OF SENSORY NERVES IN PANCREATIC-SECRETION AND CERULEIN - INDUCEDPANCREATITIS

Sensory nerves are implicated in gastroprotection and regulation of vi sceral 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 (contain ing nerve fibers) or isolated pancreatic acini, and in caerulein-induc ed pancreatitis. In conscious rats, the stimulation of sensory nerves by low dose of capsaicin given intraduodenally (0.25-0.5 mg/kg) reduce d basal pancreatic secretion, whereas dose of 1 mg/kg increased this s ecretion. Deactivation of sensory nerves by neurotoxic dose of capsaic in (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(-1 0)-10(-6) M) increased enzyme secretion and this response was abolishe d by atropine (10(-6) M) or previous deactivation of sensory nerves. I n pancreatic acini, capsaicin failed to affect basal and stimulated am ylase secretion in response to caerulein or urecholine. In intact rats , stimulatory dose of capsaicin (0.5 mg/kg i.g.) caused about 32% incr ease of pancreatic blood now and it was without any effect on the panc reatic DNA synthesis, weight, RNA, DNA and protein content. In contras t, neurotoxic dose of capsaicin caused a reduction (by 27%) in pancrea tic blood now followed by a significant decrease in RNA content and DN A synthesis in pancreatic tissue. Infusion of caerulein (10 g/kg-h) fo r 5 h produced acute edematous pancreatitis accompanied by over 60% de crease in DNA synthesis, nearly 50% inhibition of pancreatic blood flo w, and a significant increase in pancreatic weight, protein content an d plasma amylase concentration. Stimulatory dose of capsaicin attenuat ed the pancreatic tissue damage in caerulein induced pancreatitis, as manifested by a significant reversal of pancreatic blood now and DNA s ynthesis decrease. Capsaicin induced inactivation of sensory nerves pr ior to pancreatitis caused an increase of all parameters of pancreatic damage; pancreatic blood now droped by 68%, DNA synthesis decreased b y 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 an d exhibit a beneficial effect on the pancreatic integrity, mainly due to improving the pancreatic blood flow.