Psoriasis Treatment Reduces Pain Peptide Substance P in Skin, Linking Nerve Inflammation to Improvement | Research

The takeaway

Excimer light therapy reduced tissue levels of the neuropeptide substance P and its receptor NK-1R in psoriasis patients, suggesting the treatment works partly by calming neurogenic inflammation.

SP elevated in psoriasis, reduced by treatment
Psoriatic skin had significantly higher substance P than healthy skin, and excimer light therapy reduced both SP and its receptor NK-1R — correlating with clinical improvement in disease severity and itching.

What the researchers found

Psoriasis patients had significantly higher tissue levels of substance P compared to healthy controls. Excimer light therapy (9 sessions) reduced both substance P and its receptor (NK-1R) levels in psoriatic skin, along with significant clinical improvements in disease severity (PSI) and itching (VAS). The treatment was effective for both active and stable plaque psoriasis, with no significant difference between groups. This suggests excimer light works partly by dampening neurogenic inflammation mediated by substance P.

Why it matters

This study provides evidence that psoriasis is partly driven by neurogenic inflammation through the neuropeptide substance P — and that an existing treatment (excimer light) works by reducing this peptide's activity. Understanding the substance P-psoriasis connection could open the door to targeted peptide-based therapies like NK-1R antagonists for treating psoriasis and the intense itching it causes.

The numbers in context

n=54 psoriasis patients (27 stable, 27 active) + 10 controls · 9 excimer light sessions · SP levels elevated vs controls · SP and NK-1R decreased after treatment · PSI and VAS improved (p significant) · 43 patients completed treatment

How the study worked

Clinical study comparing 27 stable and 27 active psoriasis patients with 10 healthy controls. Disease severity was measured by local psoriasis severity index (PSI) and itching by visual analogue scale (VAS). Tissue levels of substance P and NK-1 receptor were measured by ELISA in skin biopsies before and after 9 excimer light sessions. 43 patients completed the treatment course.

Who was studied

54 psoriasis patients (27 stable, 27 active) and 10 healthy controls

What this study cannot tell us

The study lacked a sham/placebo control group. Sample size was moderate (54 patients total). Only tissue (not serum) levels of SP and NK-1R were measured. The study cannot determine whether excimer light directly reduces SP or whether SP reduction is secondary to overall disease improvement. Long-term durability of SP reduction and clinical improvement was not assessed.

How to read the evidence

This is a prospective clinical study with healthy controls, pre/post treatment measurements, and tissue-level biomarker analysis. The lack of a sham control limits certainty, but the correlation between SP reduction and clinical improvement is suggestive.

When this study was published

Published in 2024, this study reflects current interest in neurogenic inflammation as a treatable component of psoriasis.

The bigger picture

Neurogenic inflammation — where nerves release inflammatory peptides — is increasingly recognized as a driver of chronic skin diseases. This study connects substance P to psoriasis pathology and treatment response, adding to evidence from atopic dermatitis and other inflammatory conditions. NK-1R antagonists (substance P blockers) are being explored for chronic itch conditions, and this study supports their potential relevance to psoriasis as well.

Questions still open

Would NK-1R antagonists (substance P blockers) be effective as standalone psoriasis treatments?
Do biologic psoriasis treatments (like anti-IL-17 or anti-IL-23 antibodies) also reduce substance P levels?
Is substance P involved in the itch-scratch cycle that worsens psoriasis, and could blocking it reduce the urge to scratch?

Common questions

How does substance P contribute to psoriasis?

Substance P is released from nerve endings in the skin and triggers a cascade of inflammatory responses. In psoriasis, it activates immune cells (particularly Th17 cells), promotes blood vessel growth in plaques, and directly causes itching. This creates a neurogenic inflammation loop where nerve activation worsens the skin disease, which in turn further stimulates the nerves.

Could substance P blockers help psoriasis patients?

It's plausible. NK-1R antagonists (drugs that block substance P's receptor) are already approved for other conditions (like nausea) and are being studied for chronic itch. The finding that effective psoriasis treatment reduces SP suggests that directly blocking this peptide could be beneficial — either as a standalone therapy for itch relief or in combination with existing biologic treatments.

Read the original research

Excimer light effect on neurogenic inflammation in active versus stable psoriasis lesions.

Lasers in medical science, 39(1), 54

View on PubMed ↗Publisher’s paper ↗

Citation

El-Mesidy, Marwa S; Metwally, Yomna A; Nour, Zeinab A; Elmasry, Maha F. (2024). Excimer light effect on neurogenic inflammation in active versus stable psoriasis lesions.. Lasers in medical science, 39(1), 54. https://doi.org/10.1007/s10103-024-04005-2