Sensory neuron and substance P involvement in symptoms of a zymosan-induced rat model of acute bowel inflammation.
Intestinal inflammation is a painful syndrome with multiple symptoms, including chronic pain. This study examined the possible role of sensory neurons and substance P in symptoms of an animal model of acute intestinal inflammation. The model was induced by injecting ethanol and zymosan into the colon of anesthetized male rats. Three hours later, sections of the colon were stained with hematoxylin and eosin. To determine the role of substance P, 5 mg/kg of the neurokinin-1 receptor (NK-1r) antagonist, CP-96,345, or 300 microg/kg of an antisense oligonucleotide targeted at NK-1r mRNA was administered. Spinal cord sections were examined for internalization of NK-1r, as an indicator of substance P release. Sections of colon revealed infiltration of inflammatory cells following ethanol and zymosan treatment. Plasma extravasation in rats given ethanol and zymosan was significantly greater than in controls given saline only (P<0.0001) or saline and ethanol (P<0.001). In ethanol- and zymosan-treated rats given CP-96,345, plasma extravasation was significantly less than in rats given ethanol and zymosan without the antagonist (P<0.0001). Administration of the antisense oligonucleotide also resulted in lower levels of plasma extravasation compared with controls (P<0.01). Internalization of the NK-1r was observed in neurons of lamina I in the T13-L2 and L6-S2 regions of the spinal cord, as well as in sympathetic preganglionic neurons at the L1 level. This internalization was observed in the absence of any other stimulus besides the inflammation itself. This study implicates substance P and its receptor, the NK-1r, in acute inflammation of the colon.
Landau
A M
AM
Department of Physiology, McGill University, Montreal, Quebec, Canada.
Yashpal
K
K
Cahill
C M
CM
St Louis
M
M
Ribeiro-da-Silva
A
A
Henry
J L
JL
D000208:Acute Disease; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D003106:Colon / Q000294:innervation / Q000503:physiopathology*; D004195:Disease Models, Animal; D017615:Enteric Nervous System / Q000378:metabolism* / Q000503:physiopathology; D000431:Ethanol / Q000009:adverse effects; D018836:Inflammation Mediators / Q000009:adverse effects; D008297:Male; D020078:Neurogenic Inflammation / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D064729:Neurokinin-1 Receptor Antagonists; D009475:Neurons, Afferent / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D020671:Posterior Horn Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000378:metabolism; D013373:Substance P / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000378:metabolism; D015054:Zymosan / Q000009:adverse effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001713:Biphenyl Compounds; D018836:Inflammation Mediators; D064729:Neurokinin-1 Receptor Antagonists; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D013373:Substance P; D000431:Ethanol; D015054:Zymosan; C066892:CP 96345