Introduction
Chronic prurigo (CPG) presents clinically with multiple, typically symmetrically distributed, hyperkeratotic and erosive papules, nodules and/or plaques due to prolonged scratching and is an exceptionally severe chronic pruritic disease [
1]. It significantly affects the quality of life of those affected and is often refractory to therapy [
2]. Understanding the pathophysiology underlying CPG, especially the neuromodulatory mechanisms, is essential for the development of novel and more efficacious therapies than are currently available.
Itch is mediated by histamine‐dependent, mechano‐insensitive C-fibers (CMi-fibers) and histamine‐independent, mechano‐ and heat‐sensitive C-fibers (CMH-fibers) as well as by thinly myelinated Aδ-fibers [
3]. Peripheral sensitization of the CMH-fiber population, but not of CMi-fibers, has been demonstrated in patients with CPG compared to controls, arguing for the relevance of non-histaminergic pathways in CPG. Morphological neuronal changes have been recorded in CPG lesions, with neuronal hypertrophy in the dermis [
4] and a rarefication of peripheral nerves in the epidermis [
5]. Despite these morphological changes, however, no functional impairment of peripheral nerves could be shown in these patients [
6]. Crosstalk between keratinocytes, immunological and inflammatory cells and nerve fibers plays a pivotal role in CPG. In particular, neuropeptide substance P (SP) and calcitonin gene-related peptides (CGRP) released by sensory nerves are important for the growth and differentiation of keratinocytes [
7] as well as for neurogenic inflammation caused by vasodilatation, attraction of inflammatory cells and release of neurotrophic factors such as nerve growth factor (NGF) [
8]. In turn, neurogenic inflammation leads to an increased neuropeptide release from afferent C-fibers and—over the long term—to increased sensitivity and spontaneous activity of nerve fibers and, ultimately, to chronic pruritus [
9].
In addition to peripheral factors, central mechanisms, especially disinhibition expressed as impairment of central pain inhibitory mechanisms, may also contribute to the perpetuation and augmentation of itch in CPG.
In this review we discuss the drugs used for the antipruritic treatment of CPG that target its neuromodulatory mechanisms based on a systematic literature search of the PubMed database. The search items included combinations of the following terms: “pruritus,” “itch,” “chronic prurigo,” “prurigo nodularis,” “neuromodulation,” “hypersensitivity,” “nerves,” “therapy” and “treatment.”
This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.