Reference - Detail
| RRC ID | 61295 |
|---|---|
| Author | Vincenzi F, Targa M, Corciulo C, Tabrizi MA, Merighi S, Gessi S, Saponaro G, Baraldi PG, Borea PA, Varani K. |
| Title | Antinociceptive effects of the selective CB2 agonist MT178 in inflammatory and chronic rodent pain models. |
| Journal | Pain |
| Abstract |
Cannabinoid CB(2) receptor activation by selective agonists has been shown to produce analgesic effects in preclinical models of inflammatory, neuropathic, and bone cancer pain. In this study the effect of a novel CB(2)agonist (MT178) was evaluated in different animal models of pain. First of all, in vitro competition binding experiments performed on rat, mouse, or human CB receptors revealed a high affinity, selectivity, and potency of MT178. The analgesic properties of the novel CB(2) agonist were evaluated in various in vivo experiments, such as writhing and formalin assays, showing a good efficacy comparable with that produced by the nonselective CB agonist WIN 55,212-2. A dose-dependent antiallodynic effect of the novel CB(2) compound in the streptozotocin-induced diabetic neuropathy was found. In a bone cancer pain model and in the acid-induced muscle pain model, MT178 was able to significantly reduce mechanical hyperalgesia in a dose-related manner. Notably, MT178 failed to provoke locomotor disturbance and catalepsy, which were observed following the administration of WIN 55,212-2. CB(2) receptor mechanism of action was investigated in dorsal root ganglia where MT178 mediated a reduction of [(3)H]-d-aspartate release. MT178 was also able to inhibit capsaicin-induced substance P release and NF-κB activation. These results demonstrate that systemic administration of MT178 produced a robust analgesia in different pain models via CB(2) receptors, providing an interesting approach to analgesic therapy in inflammatory and chronic pain without CB(1)-mediated central side effects. |
| Volume | 154(6) |
| Pages | 864-73 |
| Published | 2013-6-1 |
| DOI | 10.1016/j.pain.2013.02.007 |
| PII | S0304-3959(13)00063-8 |
| PMID | 23518609 |
| MeSH | Animals Behavior, Animal / drug effects Chronic Pain / drug therapy* Chronic Pain / metabolism Diabetic Neuropathies / drug therapy* Diabetic Neuropathies / metabolism Dose-Response Relationship, Drug Female Ganglia, Spinal / drug effects Ganglia, Spinal / metabolism Humans Hyperalgesia / drug therapy* Hyperalgesia / metabolism Inflammation / drug therapy* Inflammation / metabolism Male Mice Motor Activity / drug effects Musculoskeletal Pain / drug therapy* Musculoskeletal Pain / metabolism NF-kappa B / metabolism Oxazines / agonists* Pain Measurement Quinolones / agonists* Rats Rats, Sprague-Dawley Receptor, Cannabinoid, CB2 / agonists* Rotarod Performance Test Treatment Outcome |
| IF | 5.483 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 4 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | MRMT-1(RCB2860) |