Nerve growth factor mediates activation of transient receptor potential vanilloid 1 in neurogenic pruritus of psoriasis

Pruritus is a common and painful symptom in psoriasis with profoundly negative impacts on quality of life. The underlying mechanisms of pruritus are complex and multifactorial, and accumulating evidence suggests that pruritus induced by neurogenic inflammation predominates in psoriasis. Nerve growth factor (NGF) -mediated transient receptor potential vanilloid receptor 1 (TRPV1) pathway has emerged as a crucial node in the regulation of neurogenic pruritus. TRPV1 appears coupled to most pruritus-specific molecules via the neuro-immune axis. While the modes of regulation differ for each axis, TRPV1 is involved in substantial biochemical crosstalkcausing feedback loops with significant effects on neurogenic pruritus. Therefore, TRPV1 has emerged as a target molecular in drug development for pruritus in psoriasis. However, no significant clinical progress occurred in the development of systemic TRPV1 antagonists due to elevated core temperature. Thus, topical application of TRPV1 antagonists and interference with mediators linked to the TRPV1 activation pathway may be promising therapeutic options to ameliorate pruritus. This Review focuses on recent advances in complicated regulation of NGF-mediated TRPV1 pathway in psoriatic neurogenic pruritus, as well as the therapeutic options that arise from the dissection of the pathway.

Automated summary

Pruritus is a common and painful symptom in psoriasis that greatly affects quality of life. Neurogenic inflammation induced pruritus is the predominant mechanism in psoriasis, with the nerve growth factor (NGF)-mediated TRPV1 pathway playing a crucial role. However, the development of systemic TRPV1 antagonists has been hindered by elevated core temperature. Therefore, topical application of TRPV1 antagonists and interference with TRPV1 activation pathway mediators could be promising therapeutic options. This review focuses on recent advances in understanding the complex regulation of the NGF-mediated TRPV1 pathway in psoriatic pruritus and the potential therapeutic approaches derived from this knowledge.