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 |
