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Chronic scratching increases epidermal neuronal branching and sensitivity in patients with atopic dermatitis and brachioradial pruritus, according to a recent study.

Persistent and excessive scratching can worsen itch intensity, leading to an itch–scratch cycle. This repetition causes skin barrier impairment and lichenification, characterized by enhanced inflammation and neuropathy. 

A study in Frontiers in Molecular Neuroscience assessed the effects of chronic scratching on epidermal neuroanatomy and sensory perceptions in patients with chronic inflammatory or neuropathic pruritus.

Study Population

The study comprised 69 patients and 60 age- and sex-matched healthy controls (HCs). The patient group included 35 atopic dermatitis (AD) and 34 brachioradial pruritus (BRP) patients. BRP patients were significantly older than AD patients and had a shorter pruritus duration. No differences were observed in pruritus intensity or scratch sign score between AD and BRP patients.

Reduced Intraepidermal Nerve Fiber Density in Pruritic Skin Areas

Biopsies were obtained from pruritic lichenified (PLi), pruritic non-lichenified (PNLi), or non-pruritic, non-lesional (NPNL) skin areas. Intraepidermal nerve fiber density (IENFD) analysis showed no differences between PLi and PNLi skin in either patient group. However, both pruritic areas demonstrated a significant IENFD reduction compared to NPNL skin. The IENFD was significantly reduced in all three regions of patients compared to HCs.

Branched Nerve Fibers More Prominent in Itchy Skin Areas
Branched nerve fibers were found in more than half of BRP lichenified samples, with PLi showing significantly more prominent branching than PNLi skin. The same findings were noted in AD patients. NPNL skin of patients and HCs primarily showed linear nerve fibers differing significantly from the pruritic and scratched areas. 

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Patients Itch More After Cowhage Stimulation Than Healthy Controls

NPNL skin stimulation with cowhage resulted in higher itch intensities in patients than HCs, measured by area under the curve and maximal perceived itch.

Alloknesis More Common in Lichenified Skin of BRP Patients

Alloknesis was more prevalent in lichenified skin and significantly more prevalent in the PNLi skin of BRP patients than HCs. There were no differences across testing areas in AD patients or between AD patients and HCs. The mechanically induced itch intensity in BRP patients was higher in their PLi than NPNL skin and in their PNLi skin than that of AD patients. NPNL skin showed no differences in mechanical pruritus/pain threshold in patients vs. HCs and AD vs. BRP patients.

 Half-Sine Wave Stimulation Changes AD/BRP Itching and Pain

With half-sine wave stimulation, the maximal evoked itch in AD patients was higher in PLi skin than in PNLi, NPNL, and HCs. In BRP patients, itch intensities did not differ between PLi and PNLi, but itch scores were higher in PLi than in NPNL and all areas in HCs. The maximal evoked pain in NPNL skin was higher in BRP than in HCs. AD patients perceived significantly less pain in PLi and NPNL skin than BRP patients.

With sine wave stimulation, perception thresholds in AD patients were significantly higher in PLi than in NPNL skin. Maximal evoked itch did not differ substantially between PLi and PNLi in both patient groups. Itch scores were higher in PLi than NPNL in AD, and itch intensity was higher in PNLi than NPNL in both patient groups. In BRP, maximal pain was higher in PNLi than in PLi skin. BRP patients showed higher PNLi and NPNL pain than AD patients.

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Renkhold, L., Wiegmann, H., Pfleiderer, B., Süer, A., Zeidler, C., Pereira, M. P., Schmelz, M., Ständer, S., & Agelopoulos, K. (2023). Scratching increases epidermal neuronal branching and alters psychophysical testing responses in atopic dermatitis and brachioradial pruritus. Frontiers in Molecular Neuroscience, 16. https://doi.org/10.3389/fnmol.2023.1260345