title: A Novel Nitronyl Nitroxide with Salicylic Acid Framework Attenuates Pain Hypersensitivity and Ectopic Neuronal Discharges in Radicular Low Back Pain.
abstract: Evidence has accumulated that reactive oxygen species and inflammation play crucial roles in the development of chronic pain, including radicular low back pain. Nonsteroid anti-inflammatory drugs (NSAIDs), for example, salicylic acid, aspirin, provided analgesic effects in various types of pain. However, long-term use of these drugs causes unwanted side effects, which limits their implication. Stable nitronyl (NIT) nitroxide radicals have been extensively studied as a unique and interesting class of new antioxidants for protection against oxidative damage. The present study synthesized a novel NIT nitroxide radical with salicylic acid framework (SANR) to provide synergistic effect of both antioxidation and antiinflammation. We demonstrated for the first time that both acute and repeated SANR treatment exerted dramatic analgesic effect in radicular low back pain mimicked by chronic compression of dorsal root ganglion in rats. This analgesic potency was more potent than that produced by classical NSAIDs aspirin and traditional nitroxide radical Tempol alone. Furthermore, SANR-induced behavioral analgesia is found to be mediated, at least in partial, by a reduction of ectopic spontaneous discharges in injured DRG neurons. Therefore, the synthesized NIT nitroxide radical coupling with salicylic acid framework may represent a novel potential therapeutic candidate for treatment of chronic pain, including radicular low back pain.
authors.affiliation: Institute of Neuroscience, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Han
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Wang
authors.affiliation: Class 2013, School of Clinical Medicine, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xiang-Zeng
authors.initials: XZ
authors.lastname: Liu
authors.affiliation: Institute of Neuroscience, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: San-Jue
authors.initials: SJ
authors.lastname: Hu
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Sun
authors.affiliation: Institute of Neuroscience, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Ceng
authors.initials: C
authors.lastname: Luo
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004357:Drug Synergism; D005727:Ganglia, Spinal / Q000473:pathology; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology; D007093:Imidazoles / Q000737:chemistry / Q000627:therapeutic use*; D017116:Low Back Pain / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D008297:Male; D009474:Neurons / Q000187:drug effects*; D011843:Radiculopathy / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020156:Salicylic Acid / Q000737:chemistry*; D013113:Spin Labels; D013117:Spinal Cord Compression / Q000188:drug therapy / Q000473:pathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D003497:Cyclic N-Oxides; D007093:Imidazoles; D013113:Spin Labels; D020156:Salicylic Acid; D001241:Aspirin; C001803:tempol