Journal
JOURNAL OF PHARMACOLOGICAL SCIENCES
Volume 139, Issue 4, Pages 325-332Publisher
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1016/j.jphs.2019.02.007
Keywords
Antiretroviral drug; Chemotherapeutic agent; Combination therapy; Mice model; Neuropathic pain
Categories
Funding
- Kuwait University Research Sector [PT02/15]
Ask authors/readers for more resources
Neuropathic pain sometimes occurs during chemotherapy with paclitaxel or HIV/AIDS antiretroviral therapy with nucleoside reverse transcriptase inhibitors (NRTIs). We previously reported that coadministration of indomethacin plus minocycline (IPM) was antihyperalgesic in a cannabinoid type 1 (CB1) receptor-dependent manner in a mouse model of paclitaxel-induced neuropathic pain. We evaluated if IPM combination has antihyperalgesic and antiallodynic activities in animal models of paclitaxel or NRTI (ddC, zalcitabine)-induced neuropathic pain, and whether antagonists of CB1, CB2 receptors or G proteincoupled receptor 55 (GPR55) can inhibit these activities of IPM. IPM produced antihyperalgesic and antiallodynic effects against paclitaxel and ddC-induced thermal hyperalgesia and mechanical allodynia. WIN 55,212-2, a cannabinoid receptor agonist, also had antihyperalgesic activity. The antihyperalgesic and antiallodynic activities of IPM were antagonized by a CB1 receptor antagonist AM251 and a CB2 receptor antagonist AM630, but not a GPR55 antagonist ML193. IPM had no effects on the mean time spent on the rotarod, whereas WIN 55,212-2 reduced it in a dose-dependent manner. These results show that IPM at a fixed ratio produces antihyperalgesic and antiallodynic effects in mice models of both paclitaxel and NRTI-induced neuropathic pain which is dependent on both CB1 and CB2 receptors, without causing the typical cannabinoid receptor agonist-induced motor impairment. (c) 2019 The Authors. Production and hosting by Elsevier B. V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommonsorg/licenses/by-nc-nd/4.0/).
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available