Involvement of primary afferent nerves after abdominal irradiation: consequences on ileal contractile activity and inflammatory mediator release in the rat.
In this study we analyzed the role of substance P (SP) from afferent nerves in ileum contractibility and in the release of inflammatory mediators (neurotensin, Il-1beta, and TNF-alpha) in ileal mucosa and muscularis layers after a 10-Gy gamma-irradiation of the abdomen. Six hours after irradiation, SP concentrations were lower than in control rats, and 3 days after irradiation SP-induced contractile activity was higher. Irradiation significantly increased the levels of neurotensin, Il-1beta, and TNF-alpha in both layers. Pretreatment with capsaicin depleted afferent nerve endings of SP and reduced SP levels by about 50%. Capsaicin treatment reduced SP concentrations further, beyond the levels due to irradiation, thereby suggesting that all sources of SP are affected by irradiation. Capsaicin treatment prevented the irradiation from affecting SP-induced contractile response or increasing neurotensin levels. This finding suggests that SP released by afferent nerve endings controls these functions. Proinflammatory cytokine release was not reduced by capsaicin treatment.
Institute for Radioprotection and Nuclear Safety, Human Health Protection and Dosimetry Division, Independent Section of Radiobiology Applied to Medecine, IRSN, B.P. no 17, F-92262 Fontenay-aux-Roses Cedex, France.
Christine
C
Linard
Christel
C
Marquette
Carine
C
Strup
Jocelyne
J
Aigueperse
Denis
D
Mathe
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000528:radiation effects*; D007082:Ileum / Q000276:immunology / Q000294:innervation*; D018836:Inflammation Mediators / Q000097:blood*; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D009411:Nerve Endings / Q000528:radiation effects; D009475:Neurons, Afferent / Q000528:radiation effects*; D009496:Neurotensin / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D013373:Substance P / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018836:Inflammation Mediators; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D013373:Substance P; D009496:Neurotensin; D002211:Capsaicin