Figure 5. The putative role of TRPV1 signaling in the pathogenesis and therapy of itch.

(A) Pruritogenic endovanilloids either directly or indirectly (via their own cognate receptors) activate and/or sensitize TRPV1 expressed on sensory neurons and nonneuronal cell types, which augments the bidirectional intercellular network to initiate itch. (B) Repeatedly applied topical vanilloids (such as capsaicin) may desensitize neuronal and nonneuronal TRPV1–mediated signaling so as to counteract the pruritogenic intercellular network and hence terminate itch. Note that certain cannabinoids (via acting either on specific CB receptors or directly on TRPV1) may augment the efficacy of vanilloid therapy.