![]() These observations invite consideration of both the mechanisms of action of capsaicin and menthol, and the underlying cause of this idiopathic condition. While both capsaicin and menthol application (the menthol was applied as placebo) produced a perianal burning sensation for a similar duration (about 10–15 minutes), only capsaicin relieved the itching, generally on the first day of treatment. In this issue of Gut, Lysy and colleagues 1 report that an appropriate dose of capsaicin applied topically is an effective treatment for idiopathic intractable pruritis ani. While it is argued whether itch is produced by ligands activating specific “itch fibres” and/or very localised repetitive stimuli to polymodal fibres which do not generate sufficient surround inhibition in the spinal cord, the beneficial effects of capsaicin indicate that the fibres mediating pathological itch must express the capsaicin receptor VR1. Pruritis ani may thus be a persistent hypersensitivity state triggered by inflammatory products, as NGF is known to be increased by inflammation. It is proposed that in these patients there is a phenotypic change in polymodal sensory fibres which normally express the capsaicin/heat receptor (VR1/TRPV1) but which now also express the menthol/cool receptor (TRPM8) in support, VR1 positive sensory fibres in rodents do not normally express TRPM8 but these are coexpressed and functional in nerve growth factor (NGF) rich conditions in vitro. ![]() ![]() While classical observations on functional desensitisation of nociceptors by capsaicin may explain the beneficial effects, other features and the underlying cause require consideration of recently discovered receptors and their regulators. While both capsaicin and menthol application produced a transient perianal burning sensation only capsaicin relieved the itching. Topical capsaicin is reported to be an effective treatment for idiopathic intractable pruritis ani.
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