Reactive aldehyde species–mediated neuropathic pain in spinal cord injury: Mechanisms and therapeutic opportunities

Spinal cord injury-related neuropathic pain is difficult to treat and significantly decreases quality of life. Often functionally limiting and refractory to conventional pharmacologic treatments, treating spinal cord injury-related neuropathic pain necessitates the exploration of novel mechanistic therapeutic strategies. Mounting preclinical and clinical evidence suggests that neurotoxic reactive aldehyde species such as acrolein, produced endogenously in high concentrations following spinal cord injury, are putative therapeutic targets in spinal cord injury-related neuropathic pain. The purpose of this review is to synthesize the current knowledge of mechanisms underlying reactive aldehyde species-mediated pain following spinal cord injury and propose novel drug strategies for future investigation. In doing so, we aim to highlight emerging evidence that supports the use of interventions designed to decrease reactive aldehyde species and their potential to mitigate the detrimental impacts of neuropathic pain in spinal cord injury. Ultimately, reactive aldehyde species- targeted therapeutics may have implications beyond spinal cord injury, as reactive aldehyde species play a pivotal role in the pathology of many neurological disorders.