Cannabinoid 1 and mu-Opioid Receptor Agonists Synergistically Inhibit Abdominal Pain and Lack Side Effects in Mice

• DOI: 10.1523/jneurosci.0641-22.2022
• Publication Date: 2022-08-17T17:50:16Z
• Authors: Yang Yu; Quentin K. Tsang; Josue Jaramillo-P...; Alan E. Lomax; Stephen J. Vanner; David E. Reed
• Keywords: Cannabinoid Receptor Agonists

While effective in treating abdominal pain, opioids have significant side effects. Recent legalization of cannabis will likely promote use cannabinoids as an adjunct or alternative to opioids, despite a lack evidence. We aimed investigate whether inhibit mouse colonic nociception, alone combination with at low doses. Experiments were performed on C57BL/6 male and female mice. Visceral nociception was evaluated by measuring visceromotor responses (VMR), afferent nerve mechanosensitivity flat-sheet colon preparations, excitability isolated DRG neurons. Blood oxygen saturation, locomotion, defecation measured evaluate An agonist cannabinoid 1 receptor (CB1R), arachidonyl-2′-chloroethylamide (ACEA), dose-dependently decreased VMR. ACEA HU-210 (another CB1R agonist) also attenuated mechanosensitivity. Additionally, concentration-dependently neuron excitability, which reversed the antagonist AM-251. Conversely, 2 (CB2R) agonists did not attenuate VMR, mechanosensitivity, excitability. Combination subanalgesic doses µ-opioid VMR; importantly, this analgesic effect preserved after 6 d twice daily treatment. This inhibited neuronal nitric oxide synthase guanylate cyclase inhibitors. avoided effects (decreased saturation transit) caused dose morphine. Activation CB1R, but CB2R, both synergy receptor. Thus, may enable opioid reduction avoid opioid-related <b>SIGNIFICANCE STATEMENT</b> One most cited needs for patients pain are safe treatment options. The effectiveness management is undermined severe adverse Therefore, strategies replace reduce suppress needed. study mice demonstrates that (CB1R) visceral sensation. Furthermore, markedly without causing high-dose opioids. agonists, low-dose be novel strategy pain.