The synthetic cannabinoids attenuate allodynia and hyperalgesia in a rat model of trigeminal neuropathic pain

Trigeminal neuralgia is a disorder of paroxysmal and severely disabling facial pain and continues to be a real therapeutic challenge. At present there are few effective drugs. Here we have evaluated the effects of the synthetic cannabinoid WIN 55,212-2 on mechanical allodynia and thermal hyperalgesia in a rat model of trigerninal neuropathic pain produced by a chronic constriction injury (CCI) of the infraorbital branch of the trigeminal nerve (ION). Relative to sham operation controls, rats with the CCI-ION consistently displayed hyperresponsiveness to von Frey filament and heat stimulation of the vibrissal pad. Both mechanical allodynia and thermal hyperalgesia are seen both ipsilateral and contralateral to the side of nerve injury, but is significantly more severe ipsilaterally. Administration of WIN 55,212-2 (0.3-5 mg/kg i.p.) dose-dependently increased the mechanical and heat withdrawal thresholds. WIN 55,212-2 (0.3-3 mg/kg i.p.) produced no significant motor deficits in animals using the rotarod test. The effect of WIN 55,212-2 was mimicked by cannabinoid CB I receptor agonist HU 2 10 and was antagonized by CB I receptor antagonist AM 251, but not by C132 receptor antagonist AM 630 or vanilloid receptor I antagonist capsazepine, suggesting the involveinent of CB I receptors. CCI-ION also induced a time-dependent upregulation of CB I receptors primarily within the ipsilateral superficial laminae of the trigerninal caudal nucleus revealed by both Western blot and immunohistochemistry. Taken together, these results suggest that cannabinoids may be a useful therapeutic approach for the clinical management of trigerninal neuropathic pain disorders. (c) 2007 Elsevier Ltd. All rights reserved.