Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (9): 4089-4099.doi: 10.4103/NRR.NRR-D-25-00126

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

Rachel L. Stingel1, 2, 3, Nicholas S. Race4, 5, 6, *, Riyi Shi1, 2, 3, *   

  1. 1Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA; 
    2Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA; 
    3Center for Paralysis Research, Purdue University, West Lafayette, IN, USA; 
    4Department of Physical Medicine & Rehabilitation, University of California Davis, Sacramento, CA, USA; 
    5Safar Center for Resuscitation Research, Pittsburgh, PA, USA; 
    6Association of Academic Physiatrists Rehabilitation Medicine Scientist Training Program, Owings Mills, MD, USA
  • Online:2026-09-15 Published:2026-05-16
  • Contact: Riyi Shi, MD, PhD, riyi@purdue.edu; Nicholas S. Race, MD, PhD, nsrace.mdphd@gmail.com.
  • Supported by:
    This work was supported, in part, by an early commercialization grant from the Indiana Spinal Cord & Brain Injury Research Fund from the Indiana State Department of Health (to RS and NSR). Its contents are solely the responsibility of the providers and do not necessarily represent the official views of the Indiana State Department of Health.

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Abstract: 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.

Key words: acrolein, inflammation, neuropathic pain, reactive aldehyde species, spinal cord injury