Cannabinoids and vanilloids can alleviate the hyperalgesia and allodynic that characterize neuropathic pain. This superb paper explores the relationship between cannabinoids and vanilloids, two classes of natural plant products with a separate history but apparently a lot in common.

Neuropathic pain results from injury or dysfunction of the nervous system and may play a role in the pain of PBS/IC in some patients and remains the major challenge of clinical pain therapy. Opioid treatment of neuropathic pain has proven largely unsatisfactory for its low effectiveness in some patients, the potential and development of tolerance, the risk of addiction, and the multiplicity of side effects. The efficacy of opioids may be low because of a decrease of the expression of spinal opioid receptors after injury of the peripheral nerves. Antidepressants and anticonvulsants remain the mainstays of therapy, and are effective in only about 50% of patients.

Cannabinoids have been shown effective in several animal models of neuropathic pain. There is evidence that doses that relieve neuropathic pain do not induce psychotropic effects. CB2 receptor agonists are devoid of any psychotropic effect, unlike direct CB1 receptor agonists.

In terms of the vanilloids, the desensitization induced after transient receptor potential vanilloid 1 (TRPV1) activation points to the utility of TRPV1 agonists for the treatment of various nociceptive disorders, including neuropathic pain or neurogenic inflammation. TRPV! antagonists have been described as valuable and safer agents for the treatment of inflammatory hyperalgesia and chronic pain. The authors present data in the article that leads them to hypothesize that hybrid agonists of CB1/TRPV1 receptors would be more potent than pure CB1 agonists at inhibiting pain transmission. Some endogenous CB1 agonists are also TRPV1 agonists. Some synthetic TRPV1 agonists are also CB1 agonists, or else they can cause endocannabinoid biosynthesis. When CB1 is co-localized in the same cell as TRPV1, CB1 agonists can sensitize TRPV1 to the gating by its modulators.

This interesting article points to the future strategies we can expect with regard to new drug development for the treatment of chronic neuropathic pain, and is worth a read for those interested in treating the pain of BPS/IC.

Sabatino Maione, Katarzyna Starowicz, Enza Palazzo, Francesco Rossi, Vincenzo Di Marzo

Drug Development Research 67:339-354, 2006.

UroToday.com Painful Bladder Syndrome Section

Written by Philip M. Hanno, MD, a Contributing Editor with UroToday.

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