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Analgesia and mouse strain influence neuromuscular plasticity in inflamed intestine
Author(s) -
Blennerhassett M. G.,
Lourenssen S. R.,
Parlow L. R. G.,
Ghasemlou N.,
Winterborn A. N.
Publication year - 2017
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.13097
Subject(s) - colitis , inflammatory bowel disease , ulcerative colitis , medicine , inflammation , immunology , cecum , cytokine , disease , pharmacology , pathology , gastroenterology
Background Mouse models of inflammatory bowel disease (IBD) identify an impact on the enteric nervous system (ENS) but do not distinguish between Crohn's disease and ulcerative colitis phenotypes. In these models, analgesia is required, but its influence on different strains and disease outcomes is unknown. Therefore, changes to the ENS and intestinal smooth muscle were studied in trinitrobenzene sulfonic acid (TNBS) and dextran sodium sulfate (DSS) induced colitis to identify the effects of analgesia, and compared between two mouse strains. Methods Colitis was induced in CD1 or BALB/c mice receiving analgesia with either buprenorphine or tramadol. Euthanasia was on Day 8 (DSS) or Day 4 (TNBS). Outcomes were Disease Activity Index and cytokine assay, and quantitative histology and immunocytochemistry were used to evaluate effects of inflammation on neurons and smooth muscle. Key Results In BALB/c mice, both models of colitis caused >2‐fold increase in smooth muscle cell number. DSS caused axon proliferation without neuron loss while TNBS caused significant neuron loss and axonal damage. Buprenorphine (but not tramadol) was generally anti‐inflammatory in both strains, but correlated with lethal outcomes to TNBS in BALB/c mice. Conclusions and Inferences Smooth muscle growth is common to both models of colitis. In contrast, ENS damage in TNBS is correlated with the severe response of a Crohn's disease‐like phenotype, while DSS correlates with a milder, ulcerative colitis‐like outcome in the deeper tissues. Analgesia with tramadol over buprenorphine is supported for mouse studies of IBD.