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.
Highlights
Radicular low back pain represents a frequent and poorly understood medical problem
We have for the first time synthesized a novel NIT nitroxide radical with salicylic acid framework (SANR) exerting the beneficial effects of both the Nonsteroid anti-inflammatory drugs (NSAIDs) and the antioxidants (Figure 1). We demonstrated that both acute and long-term systemic administration of SANR attenuated the mechanical hypersensitivity and thermal hyperalgesia observed in an experimental model of Chronic Compression of DRG (CCD) rats
Oxidative stress and inflammation have long been assumed to be involved in the development and maintenance of chronic pain [1, 9, 10]
Summary
Radicular low back pain represents a frequent and poorly understood medical problem. It is a major cause of disability and higher health care costs in the world. We have for the first time synthesized a novel NIT nitroxide radical with salicylic acid framework (SANR) exerting the beneficial effects of both the NSAIDs and the antioxidants (Figure 1). We demonstrated that both acute and long-term systemic administration of SANR attenuated the mechanical hypersensitivity and thermal hyperalgesia observed in an experimental model of CCD rats. When compared to the same concentration of Tempol or aspirin, SANR exhibited a much stronger analgesic effect Taken together, these findings clearly suggest that synthesis of new NIT nitroxyl radical with salicylic acid framework may represent a potential new candidate for the treatment of radicular low back pain
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