Pathophysiology and management of burn injury-induced pain.

This review examines the pathophysiology and therapeutic management of burn injury-induced pain (BIP). Burn injury, occurring globally in about 11 million people, often induces the most intense pain, but its management remains suboptimal. The pain often persists even after complete wound healing and hospital discharge causing both long-term disability and neurological dysfunction. The fact that BIP persists well beyond the initial hospitalization is not well recognized and should be underscored as the pain involves even non-burned areas. The pathophysiology of the latter problem is poorly understood and needs further study. Opioids, the mainstay for moderate to severe pain relief after major burn injury, with time, have poor analgesic and serious side effects. Accurate assessment pain of BIP and its biology at different stages of treatment helps to provide effective treatments of the different etiological factors that cause BIP and their sequelae. Based on clinical and pre-clinical studies, we discuss the current knowledge on the underlying cellular and molecular mechanisms in the initiation and persistence of BIP during the acute phase and later phases of injury. Opioid receptor-mediated signaling changes and immune microglia responses in concert exaggerate nociceptive behavior. Both burn injury and opioids upregulate spinal NMDA receptor expression and microglia changes, which further exaggerate pain. BIP has inflammatory and neuropathic components. Pharmacological and non-pharmacological approaches currently available for management of BIP is discussed. Areas that need further study include the role of other central and peripheral factors in the exaggeration of pain well beyond wound healing. Novel non-opioid methods to rectify BIP is important to develop in view of the potential for opioid use disorder. The role of microbiome in chronic pain syndromes is an unexplored territory and its relevance to BIP needs further examination. Pruritus or itch, though very common and important in the pharmacotherapy of burns, the discussion of this topic is brief. Extensive review of this topic is beyond the scope of this review in view of the vast body of knowledge and varying and multiple treatment options.