Vanilloid receptor desensitization as a strategy for improving glucose tolerance as well as reducing diabetic neuropathic pain

The vanilloid capsaicin has long been known to desensitize pain pathways leading to long-term analgesia through selectively binding to small unmyelinated sensory afferent nerves.  However the pungency and systemic toxicity of capsaicin has largely precluded its therapeutic utility. Recent data published by Dorte X. Gram from Novo Nordisk A/S are now emerging to suggest that sensory afferents might also be implicated in the development of glucose intolerance. The present study reports that sensory nerve desensitization by resiniferatoxin, a capsaicin analogue with reduced relative pungency compared to capsaicin is able to improve glucose tolerance, increase glucose-induced insulin release and inhibit DPPIV (dipeptidyl peptidase IV) activity. Hence, either resiniferatoxin,  its synthetic analogues or other compounds that can downregulate sensory nerve activity could offer a novel approach to metabolic control as well as neuropathic pain that develops in response to prolonged metabolic imbalance...[more]

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