Molecular Mechanisms Underlying Burn-Injury Induced Pain: From Inflammation to Epigenetics

In modern warfare, blast and burn insults account for over half of combat injuries. Burn-injured Service Members represent one military patient population in need of a pain management regimen that involves optimal acute pain control, reduced chronic pain, and reduced risk of addiction. Burn pain is a significant clinical problem. The current standard of care can result in decreasing analgesia or the need for dosage escalation that incurs an increased risk of significant side effects. This review describes the current understanding of many important structures and mechanisms associated with burn pain, and these subjects provide promising targets for novel analgesics.

An independent literature retrieval was performed by all authors using a combination of search terms, including "burn" and "pain," alongside "glia," "receptors," "brain," "allodynia," "hyperalgesia," "central sensitization," "inflammation," and "tolerance." The search encompassed renowned reference repositories, namely PubMed (MEDLINE) and Scopus.

Burn injuries are accompanied by complex pain originating after thermal insult, and this pain persists through treatment procedures like debridement, wound dressing, grafting, and wound closure. Understanding the molecular mechanisms that persist following burn injury is critical. This review highlights specific topics, including receptors and brain anatomy pertinent to pain, burn-induced allodynia and hyperalgesia, central sensitization, molecular signatures of burn-induced nociception and pain, and opioid analgesic tolerance.

Interventions to accelerate burn injury healing and/or diminish the deleterious effects of dysregulated inflammatory and immune responses following severe burn are needed. Therefore, elucidating the underlying molecular mechanisms of burn-injury induced pain is of the utmost importance.