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Activation of cannabinoid receptor 2 attenuates mechanical allodynia and neuroinflammatory responses in a chronic post‐ischemic pain model of complex regional pain syndrome type I in rats
Author(s) -
Xu Jijun,
Tang Yuying,
Xie Mian,
Bie Bihua,
Wu Jiang,
Yang Hui,
Foss Joseph F.,
Yang Bin,
Rosenquist Richard W.,
Naguib Mohamed
Publication year - 2016
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.13414
Subject(s) - neuropathic pain , neuroinflammation , medicine , allodynia , agonist , microglia , cannabinoid receptor type 2 , anesthesia , neuroprotection , pharmacology , complex regional pain syndrome , chronic pain , hyperalgesia , cannabinoid receptor , neuroscience , nociception , receptor , inflammation , psychology , psychiatry
Abstract Complex regional pain syndrome type 1 ( CRPS ‐I) remains one of the most clinically challenging neuropathic pain syndromes and its mechanism has not been fully characterized. Cannabinoid receptor 2 ( CB 2) has emerged as a promising target for treating different neuropathic pain syndromes. In neuropathic pain models, activated microglia expressing CB 2 receptors are seen in the spinal cord. Chemokine fractalkine receptor ( CX 3 CR 1) plays a substantial role in microglial activation and neuroinflammation. We hypothesized that a CB 2 agonist could modulate neuroinflammation and neuropathic pain in an ischemia model of CRPS by regulating CB 2 and CX 3 CR 1 signaling. We used chronic post‐ischemia pain ( CPIP ) as a model of CRPS ‐I. Rats in the CPIP group exhibited significant hyperemia and edema of the ischemic hindpaw and spontaneous pain behaviors (hindpaw shaking and licking). Intraperitoneal administration of MDA 7 (a selective CB 2 agonist) attenuated mechanical allodynia induced by CPIP . MDA 7 treatment was found to interfere with early events in the CRPS ‐I neuroinflammatory response by suppressing peripheral edema, spinal microglial activation and expression of CX 3 CR 1 and CB 2 receptors on the microglia in the spinal cord. MDA 7 also mitigated the loss of intraepidermal nerve fibers induced by CPIP . Neuroprotective effects of MDA 7 were blocked by a CB 2 antagonist, AM 630. Our findings suggest that MDA 7, a novel CB 2 agonist, may offer an innovative therapeutic approach for treating neuropathic symptoms and neuroinflammatory responses induced by CRPS ‐I in the setting of ischemia and reperfusion injury.