Effects of sensory denervation by neonatal capsaicin administration on experimental pancreatitis induced by dibutyltin dichloride.
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.
Ikeura
Tsukasa
T
Department of Anatomy and Cell Science, Kansai Medical University, Fumizonocho 10-15, Moriguchi City, Osaka 570-8506, Japan.
Kataoka
Yosky
Y
Wakabayashi
Taketoshi
T
Mori
Tetsuji
T
Takamori
Yasuharu
Y
Takamido
Shoichiroh
S
Okazaki
Kazuichi
K
Yamada
Hisao
H
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D000831:Animals, Newborn; D002211:Capsaicin / Q000008:administration & dosage* / Q000494:pharmacology*; D003714:Denervation; D005260:Female; D007150:Immunohistochemistry; D009475:Neurons, Afferent / Q000502:physiology*; D009947:Organotin Compounds; D010179:Pancreas / Q000294:innervation*; D010195:Pancreatitis / Q000139:chemically induced / Q000601:surgery*; D050500:Pancreatitis, Chronic / Q000139:chemically induced / Q000601:surgery; D011247:Pregnancy; D051381:Rats; D011917:Rats, Inbred Lew; D013373:Substance P / Q000378:metabolism
D009947:Organotin Compounds; D013373:Substance P; D000681:Amylases; C020735:dibutyldichlorotin; D002211:Capsaicin