MODULATION OF PANCREATIC-SECRETION BY CAPSAICIN-SENSITIVE SENSORY NEURONS IN THE RAT

The purpose of this work was to study whether stimulation or destructi on of sensory afferents can modulate pancreatic secretion. The neuroto xin capsaicin is specific for a subpopulation of small diameter primar y afferent neurons. Small doses of capsaicin were administered to anes thetized rats as intraduodenal or intragastric bolus injections to sti mulate digestive sensory fibers, and pancreatic secretory response was measured. In addition, several high-dose subcutaneous capsaicin injec tions were administered 10 days before the experiments began, in order to inactivate sensory fibers. Basal and 2-deoxy-D-glucose (2DG)-stimu lated pancreatic secretion was then measured. Intraduodenal capsaicin (96-3,050 mu g/kg) induced a progressive (peak response 40-60 min afte r the injection), dose-related and long-lasting (>180 min) increase in pancreatic output of sodium, bicarbonate, and total protein. The maxi mal response was obtained with 964 mu g/kg capsaicin; it amounted to a bout 15% of the maximal response to exogenous cholecystokinin octapept ide (CCK8). The response was not decreased by atropine, hexamethonium, vagotomy, a mixture of adrenoceptor antagonists (prazosin + idazoxan + propranolol), or by the CCKB receptor antagonist L365,260. In contra st, the CCKA receptor antagonist L364,718 reduced by 30-40% the sodium and bicarbonate response and reduced by 90% the protein response indu ced by capsaicin, but not the response induced by methacholine or 2DG. However, intraluminal capsaicin did not release CCK in a preparation of isolated perfused duodenojejunum. Intragastric capsaicin did not si gnificantly change pancreatic secretion. Capsaicin pretreatment had no effect on basal and 2DG-stimulated secretion, but abolished the respo nse to intraduodenal capsaicin. In conclusion, intraduodenal capsaicin can stimulate external pancreatic secretion in anesthetized rats thro ugh capsaicin-sensitive sensory neurons. This effect is not dependent on vagal nerves, adrenergic receptors, and cholinergic (nicotinic and muscarinic) receptors, but instead involves CCK, receptors (probably l ocated on neurons). Primary afferent denervation by capsaicin does not interfere with the 2DG-activated efferent vagal pathway.