Submission ID 93201

Poster Code HR-P-93
Title of Abstract Acute colitis alters the effects of cannabinoid and opioid receptor agonists on colonic nociception
Abstract Submission Background/Aim: Abdominal pain is a debilitating symptom of inflammatory bowel disease. We have shown that the combination of sub-analgesic concentrations of cannabinoid 1 receptor (CB1R) and mu-opioid receptor (MOR) agonists inhibit colonic pain signalling in non-inflamed mice and is devoid of side effects. This study investigated the effect of cannabinoid and MOR agonists alone or in combination on colonic nociception during acute colitis. Methods: Dextran sulfate sodium administration induced colitis in male and female C57BL/6 mice. Colonic pain signalling was assessed by measuring the visceromotor response (VMR) to colorectal distension (20-80 µL) in vivo and mechanosensitivity of single colonic afferent axons in ex vivo extracellular afferent nerve recordings. Data were analyzed using a one- or two-way ANOVA with Bonferroni test. N= number of mice; n=number of single axons. Results: ACEA (CB1R agonist; 3 mg/kg), effective in healthy mice, did not inhibit VMR in mice with colitis (p=0.55, N=6). Conversely, HU-308 (CB2R agonist; 3 mg/kg), which had no effect in healthy mice, inhibited VMR in colitis compared to vehicle (32% reduction, p<0.05, N=6). While morphine (MOR agonist; 0.3 mg/kg) had no effect in healthy mice, it inhibited VMR during colitis (34% reduction, p<0.01, N = 8). Interestingly, the effect of combining low dose ACEA (0.3 mg/kg) and morphine (0.3mg/kg) was larger than that of morphine alone (62% vs. 34% reduction; p=0.06, N=5-8). While ACEA (1µM) inhibited colonic mechanosensitivity in healthy mice, ACEA (10 µM) was required in colitis (15.2 vs. 11.6 Hz; p<0.05, n=11, N=6). However, combining sub-analgesic concentrations of ACEA (100 nM) and DAMGO (MOR agonist;1 nM) still significantly reduced mechanosensitivity (18.4 vs. 12.0 Hz; p<0.05, n=7, N=5). Conclusions: During colitis, the effectiveness of CB1R, CB2 and MOR agonists on pain signaling is altered. However, combining sub-analgesic CB1R and MOR agonists is still more effective than the MOR agonist alone.
Please indicate who nominated you Faculty of Health Science, Queen's University
What Canadian Institutes of Health Research (CIHR) institute is your research most closely aligned? Neurosciences, Mental Health and Addiction
Nutrition, Metabolism and Diabetes
What Canadian Institutes of Health Research (CIHR) pillar of health research does your research fall under? Biomedical
PDF of abstract Tsang ICAM 2023 Abstract_Feb 7 2023.pdf
2023-02-08 at 14:27:55
Presenter and Author(s) Quentin Tsang
Quentin Tsang
Hailey Schincariol
Claudius Degro
Alan Lomax
Stephen Vanner
David Reed

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