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Burn scar pain: from mechanisms to treatments

Minjuan Zhao1

  • 1Department of Burns, First People's Hospital of Shangqiu City, Shangqiu, Henan, China.

Frontiers in Physiology
|October 10, 2025
PubMed

Insights

Burn scars cause chronic pain and fibrosis, resisting treatment. Understanding scar-nerve crosstalk is key to developing targeted therapies for improved patient outcomes.

Area of Science:

  • Regenerative Medicine
  • Neuroscience
  • Dermatology

Background:

  • Chronic burn scars significantly impair quality of life and resist empirical treatments.
  • Existing research identifies scar fibrosis and nociception mediators, but lacks pathway integration.
  • There is an urgent need for mechanism-based therapies for burn scars and associated pain.

Purpose of the Study:

  • To comprehensively review molecular and cellular drivers of burn scar formation.
  • To elucidate the bidirectional interactions between scar tissue and nerve regeneration.
  • To explore mechanisms of long-term scar pain and emerging treatment strategies.

Main Methods:

  • Review of molecular and cellular drivers, focusing on transforming growth factor-β (TGF-β) in fibroblast activation and extracellular matrix remodeling.
  • Analysis of neuropeptide-mediated (Nerve Growth Factor, Substance P, CGRP) interactions between scar tissue and nerve regeneration.
  • Examination of pain mechanisms including peripheral/central sensitization (TRPV1/Nav channels) and neuroinflammation.
  • Survey of emerging treatments targeting these pathways (laser, ESWT, regenerative injections, TRP antagonists).

Main Results:

  • Transforming growth factor-β (TGF-β) is a key mediator of fibroblast activation and extracellular matrix remodeling in burn scars.
  • Neuropeptides facilitate bidirectional communication between scar tissue and regenerating nerves.
  • Peripheral and central sensitization via TRPV1/Nav channels and neuroinflammation contribute to chronic scar pain.
  • Emerging therapies like laser, ESWT, regenerative injections, and TRP antagonists show promise.

Conclusions:

  • A detailed understanding of scar-nerve crosstalk at the molecular level is critical.
  • Targeted interventions based on scar-nerve interactions can improve long-term outcomes for burn patients.
  • Mechanism-based therapies are essential for addressing the challenges of chronic burn scars and pain.
Keywords:
burnsmanagementpainscars (cicatrix)treatment

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