title: Acrolein involvement in sensory and behavioral hypersensitivity following spinal cord injury in the rat.
abstract: Growing evidence suggests that oxidative stress, as associated with spinal cord injury (SCI), may play a critical role in both neuroinflammation and neuropathic pain conditions. The production of the endogenous aldehyde acrolein, following lipid peroxidation during the inflammatory response, may contribute to peripheral sensitization and hyperreflexia following SCI via the TRPA1-dependent mechanism. Here, we report that there are enhanced levels of acrolein and increased neuronal sensitivity to the aldehyde for at least 14 days after SCI. Concurrent with injury-induced increases in acrolein concentration is an increased expression of TRPA1 in the lumbar (L3-L6) sensory ganglia. As proof of the potential pronociceptive role for acrolein, intrathecal injections of acrolein revealed enhanced sensitivity to both tactile and thermal stimuli for up to 10 days, supporting the compound's pro-nociceptive functionality. Treatment of SCI animals with the acrolein scavenger hydralazine produced moderate improvement in tactile responses as well as robust changes in thermal sensitivity for up to 49 days. Taken together, these data suggest that acrolein directly modulates SCI-associated pain behavior, making it a novel therapeutic target for preclinical and clinical SCI as an analgesic. Following spinal cord injury (SCI), acrolein involvement in neuropathic pain is likely through direct activation and elevated levels of pro-nociceptive channel TRPA1. While acrolein elevation correlates with neuropathic pain, suppression of this aldehyde by hydralazine leads to an analgesic effect. Acrolein may serve as a novel therapeutic target for preclinical and clinical SCI to relieve both acute and chronic post-SCI neuropathic pain.
authors.affiliation: Department of Anesthesia, Indiana University School of Medicine.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Due
authors.affiliation: Department of Basic Medical Sciences, School of Veterinary Medicine, and Weldon School of Biomedical Engineering, Purdue University.
authors.forename: Jonghyuck
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Basic Medical Sciences, School of Veterinary Medicine, and Weldon School of Biomedical Engineering, Purdue University.
authors.forename: Lingxing
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Basic Medical Sciences, School of Veterinary Medicine, and Weldon School of Biomedical Engineering, Purdue University.
authors.forename: Michael
authors.initials: M
authors.lastname: Walls
authors.affiliation: Department of Cell Biology and Anatomy, Indiana University School of Medicine.
authors.forename: Yohance M
authors.initials: YM
authors.lastname: Allette
authors.affiliation: Department of Anesthesia, Indiana University School of Medicine.|Department of Cell Biology and Anatomy, Indiana University School of Medicine.
authors.forename: Fletcher A
authors.initials: FA
authors.lastname: White
authors.affiliation: Department of Anesthesia, Indiana University School of Medicine.|Department of Basic Medical Sciences, School of Veterinary Medicine, and Weldon School of Biomedical Engineering, Purdue University.
authors.forename: Riyi
authors.initials: R
authors.lastname: Shi
mesh_terms: D000171:Acrolein / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015153:Blotting, Western; D003080:Cold Temperature; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D055724:Electrophysiological Phenomena / Q000187:drug effects; D017950:Ganglia, Sensory / Q000378:metabolism / Q000473:pathology; D006358:Hot Temperature; D006830:Hydralazine / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007278:Injections, Spinal; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D009437:Neuralgia / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D009619:Nociceptors / Q000502:physiology; D010523:Peripheral Nervous System Diseases / Q000378:metabolism / Q000473:pathology; D010812:Physical Stimulation; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012021:Reflex, Abnormal / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology*; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat; D006830:Hydralazine; D012313:RNA; D000171:Acrolein
keywords: TRPA1; aldehyde; hydralazine; hyperreflexia; lipid peroxidation; proalgesic