Extrinsic surgical denervation inhibits Clostridium difficile toxin A-induced enteritis in rats.
Clostridium difficile enteritis is caused by toxin A (TA) which stimulates substance P release and subsequent receptor activation. This receptor stimulation results in secretion, inflammation, and structural damage. However, it is unclear as to which subset of neurons is required to initiate substance P release following toxin stimulation. Five centimeter ileal segments were surgically denervated. After 10 days, three ileal loops were constructed in each rat: the denervated loop was injected intraluminally with 5 microg of TA and two intact loops were injected with TA or vehicle, respectively. Ileal secretion, myeloperoxidase activity, and histology were then assessed. Denervated ileal loops injected with TA had a 75% reduction in ileal secretion (P < 0.001), 92% reduction in myeloperoxidase activity (P < 0.01) and 96% reduction in histologic damage (P < 0.001) compared to innervated loops. There were no significant differences between the denervated loops injected with TA and those injected with vehicle. Extrinsic surgical denervation results in protection of ileal loops from TA enteritis. Furthermore, these results exclude the participation of intrinsic enteric nerves in TA-induced ileal damage. Finally, this suggests that extrinsic primary sensory neurons mediate the effects of intraluminal TA in the ileum.
Mantyh
C R
CR
Department of Surgery, Durham VA Medical Center, Durham, NC 27710, USA.
McVey
D C
DC
Vigna
S R
SR
D000818:Animals; D017763:Autonomic Denervation; D001427:Bacterial Toxins / Q000494:pharmacology*; D016360:Clostridioides difficile; D017615:Enteric Nervous System / Q000382:microbiology / Q000601:surgery; D004761:Enterocolitis, Pseudomembranous / Q000139:chemically induced / Q000517:prevention & control / Q000601:surgery*; D004768:Enterotoxins / Q000494:pharmacology*; D007082:Ileum / Q000201:enzymology / Q000294:innervation / Q000382:microbiology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000378:metabolism
D001427:Bacterial Toxins; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile; D013373:Substance P; D009195:Peroxidase