Meet Substance P: The Neuropeptide Behind Some of Your Most Frustrating Skin Symptoms 

Written By Varun Batra

If you’ve ever wondered why stress makes your skin flare, why itching triggers more itching, or why wounds heal slower in nerve-damaged skin — the answer often comes back to one molecule: Substance P (SP). 

What Is Substance P? 

SP is a neuropeptide stored in sensory nerves. When skin is irritated, stressed, or injured, nerves release SP into the surrounding tissue. 

SP Can Trigger: 

  1. Inflammation 

  • SP activates immune cells 

  • It increases TNF-α, IL-1, IL-6 

  • It releases histamine from mast cells 

  1. Vasodilation (Redness + Heat) 

  • SP widens blood vessels and increases blood flow. 

  1. Immune Activation 

  • SP boosts T cell activity and antibody production. 

  1. Itching & Pain Sensitisation 

  • SP amplifies itch pathways, especially in chronic eczema, psoriasis, or neuropathic conditions. 

 

SP Is Implicated in Many Conditions 

  • Atopic dermatitis 

  • Psoriasis 

  • Chronic itching 

  • Stress-related flares 

  • Hidradenitis suppurativa 

  • Neurogenic rosacea 

  • Chronic wounds 

Reducing SP Activity Can Help 

Emerging research focuses on: 

  • Neurokinin-1 receptor (NK1R) blockers 

  • Stress management 

  • Anti-inflammatory treatments 

  • Phototherapy 

  • Topicals that reduce nerve activation 

Why This Matters 

SP helps explain why psychological stress leads to physical skin changes. The brain–skin axis is real, and SP is one of its main messengers. 

Reference: 

Ansel, J.C., Kaynard, A.H., Armstrong, C.A., Olerud, J., Bunnett, N. and Payan, D. (1996). Skin-Nervous System Interactions. Journal of Investigative Dermatology, [online] 106(1), pp.198–204. doi:https://doi.org/10.1111/1523-1747.ep12330326. 

Varun Batra
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