Peripheral sensitisation and loss of descending inhibition is a hallmark of chronic pruritus

Abstract Neurophysiological mechanisms leading to chronicity of pruritus are not yet fully understood and it is not known whether these mechanisms diverge between different underlying diseases of chronic pruritus. This study aimed to detect such mechanisms in chronic pruritus of various origins. One-hundred and twenty patients with chronic pruritus of inflammatory origin (atopic dermatitis), neuropathic origin (brachioradial pruritus) and chronic prurigo of nodular type, the latter as a model for chronic scratching, as well as 40 matched healthy controls participated in this study. Stimulation with cowhage induced a more intensive itch sensation compared to stimulation with other substances in all patient groups but not in healthy controls, arguing for sensitisation of cutaneous mechano- and heat-sensitive C-fibers in chronic pruritus. All patient groups showed a decreased intraepidermal nerve fibre density compared to controls. A decreased condition pain modulation effect was observed in all patient groups compared to controls, suggesting a reduced descending inhibitory system in chronic pruritus. In sum, chronic pruritus of different etiology showed a mixed peripheral and central pattern of neuronal alterations, which might contribute to the chronicity of pruritus with no differences between pruritus entities. Our findings may contribute to the development of future treatment strategies targeting these pathomechanisms.