Increase in the number of intrapancreatic sensory nerve fibers has been implicated in the generation of
pain in
chronic pancreatitis. Because some sensory
neurotransmitters (e.g.,
substance P) are known to have proinflammatory effects, we hypothesized that
denervation of intrapancreatic nerves might influence not only
pain generation but also
inflammation. Neonatal Lewis rats were injected with
capsaicin (50 mg/kg or 0 mg/kg), a
neurotoxin, to induce
denervation of primary sensory neurons. When rats reached 170-190 g
body weight, experimental
pancreatitis was induced by a single administration of
dibutyltin dichloride (7 mg/mg). The severity of
pancreatitis was evaluated in both groups in the acute phase (at 3 and 7 days) and chronic phase (at 28 days). At day 7, the sensory
denervation induced by neonatal
capsaicin administration inhibited pancreatic
inflammation on both histological (determination of interstitial
edema, expansion of interlobular septa and intercellular spaces, and inflammatory cell infiltration) and biochemical (intrapancreatic
myeloperoxidase activity) evaluation. Furthermore, at day 28, glandular
atrophy, pseudotubular complexes, and rate of
fibrosis were each significantly lower in the
capsaicin-pretreated group than in the vehicle-pretreated group. Our findings provide in vivo evidence that primary sensory neurons play important roles in both
acute pancreatitis and chronic pancreatic
inflammation with
fibrosis.