The endocannabinoid and endovanilloid systems and their interactions in neuropathic pain

Under physiological conditions, nociception has a protective role, allowing an individual to react appropriately to the noxious stimulus and to minimize its effects. On the contrary, chronic pain arises from damage to the nervous system and is persistent. Mechanisms, symptoms, and signs of neuropathic pain have been the subject of extensive studies, but still there is no single, well‐tolerated drug that is effective in all types of neuropathic pain. Currently, there is a growing amount of evidence on the analgesic properties of cannabinoids in nociceptive pathways. Interestingly, recent data also implicate an endogenous cannabinoid ligand, anandamide, as an agonist at the capsaicin VR1/TRPV1 receptor. Herein, we review the available evidence in favour of cannabinoid and vanilloid alleviation of hyperalgesia and allodynia, two typical symptoms of neuropathic pain. The most important findings regarding CB1, TRPV1 receptors, and neuropathic pain are discussed in detail. We also consider the implications of combined studies correlating the endocannabinoid and vanilloid signalling systems as promising therapeutic approaches for new analgesic drugs. Collectively, the investigations reviewed here support the use of drugs targeting the endocannabinoid and endovanilloid systems in the treatment of chronic inflammation and neuropathic pain states. Drug Dev. Res. 67:339–354, 2006.