کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5548930 1556601 2017 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synergistic attenuation of chronic pain using mu opioid and cannabinoid receptor 2 agonists
ترجمه فارسی عنوان
ضعیف شدن سونوگرافی درد مزمن با استفاده از آگونیست های گیرنده دوم کانابینوئید و اوپوئیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
چکیده انگلیسی


- Opioid use is associated with undesirable side effects, including addiction.
- Dual-targeting MOR and CB2 receptors results in analgesic synergy.
- Co-administration of MOR-CB2 reduces opioid-induced increases in reward.

The misuse of prescription opiates is on the rise with combination therapies (e.g. acetaminophen or NSAIDs) resulting in severe liver and kidney damage. In recent years, cannabinoid receptors have been identified as potential modulators of pain and rewarding behaviors associated with cocaine, nicotine and ethanol in preclinical models. Yet, few studies have identified whether mu opioid agonists and CB2 agonists act synergistically to inhibit chronic pain while reducing unwanted side effects including reward liability. We determined if analgesic synergy exists between the mu-opioid agonist morphine and the selective CB2 agonist, JWH015, in rodent models of acute and chronic inflammatory, post-operative, and neuropathic pain using isobolographic analysis. We also investigated if the MOR-CB2 agonist combination decreased morphine-induced conditioned place preference (CPP) and slowing of gastrointestinal transit. Co-administration of morphine with JWH015 synergistically inhibited preclinical inflammatory, post-operative and neuropathic-pain in a dose- and time-dependent manner; no synergy was observed for nociceptive pain. Opioid-induced side effects of impaired gastrointestinal transit and CPP were significantly reduced in the presence of JWH015. Here we show that MOR + CB2 agonism results in a significant synergistic inhibition of preclinical pain while significantly reducing opioid-induced unwanted side effects. The opioid sparing effect of CB2 receptor agonism strongly supports the advancement of a MOR-CB2 agonist combinatorial pain therapy for clinical trials.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 116, April 2017, Pages 59-70
نویسندگان
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