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A Novel Nitronyl Nitroxide with Salicylic Acid Framework Attenuates Pain Hypersensitivity and Ectopic Neuronal Discharges in Radicular Low Back Pain.

Han WJ, Chen L, Wang HB, Liu XZ, Hu SJ, Sun XL, Luo C - Neural Plast. (2015)

Bottom Line: However, long-term use of these drugs causes unwanted side effects, which limits their implication.The present study synthesized a novel NIT nitroxide radical with salicylic acid framework (SANR) to provide synergistic effect of both antioxidation and antiinflammation.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neuroscience, Fourth Military Medical University, Xi'an 710032, China.

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.

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Structure of SANR and other nitroxide radicals. Structure of TEMPO, α-nitronyl (NIT) group radicals, Tempol, and SANR.
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fig1: Structure of SANR and other nitroxide radicals. Structure of TEMPO, α-nitronyl (NIT) group radicals, Tempol, and SANR.

Mentions: Much evidence has accumulated that reactive oxygen species (ROS) play an important role in the development of chronic pain [9, 10]. Various ROS scavengers and antioxidants provided analgesic effects in animal models of inflammatory and neuropathic pain [9, 11–15]. In recent years, nitroxide radicals have been extensively studied as a unique and interesting class of antioxidants to protect against ionizing radiation [16], ischemia/reperfusion injury [17], neurodegenerative diseases [18, 19], and chronic pain [9, 11–14]. Some nitroxide radicals, for example, amifostine, are being used in clinical practice [20]. Unlike other antioxidants that act in a sacrificial mode, nitroxide radicals act as self-replenishing antioxidants in a catalytic manner. The TEMPO and α-nitronyl (NIT) groups are the two major kinds of nitroxide radicals (Figure 1). Tempol (4-hydroxy-2,2,6,6-tetramethylpiper-idine-N-oxyl), a kind of TEMPO, is found to alleviate pain in various experimental pain models [12–15, 21]. Compared with Tempol, NIT group nitroxide radicals have an extensive distribution of unpaired spin density. As such, much attention has been levied towards the development of this kind of new NIT nitroxyl radicals. However, whether NIT group NRs possess antinociceptive action has remained elusive.


A Novel Nitronyl Nitroxide with Salicylic Acid Framework Attenuates Pain Hypersensitivity and Ectopic Neuronal Discharges in Radicular Low Back Pain.

Han WJ, Chen L, Wang HB, Liu XZ, Hu SJ, Sun XL, Luo C - Neural Plast. (2015)

Structure of SANR and other nitroxide radicals. Structure of TEMPO, α-nitronyl (NIT) group radicals, Tempol, and SANR.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4644553&req=5

fig1: Structure of SANR and other nitroxide radicals. Structure of TEMPO, α-nitronyl (NIT) group radicals, Tempol, and SANR.
Mentions: Much evidence has accumulated that reactive oxygen species (ROS) play an important role in the development of chronic pain [9, 10]. Various ROS scavengers and antioxidants provided analgesic effects in animal models of inflammatory and neuropathic pain [9, 11–15]. In recent years, nitroxide radicals have been extensively studied as a unique and interesting class of antioxidants to protect against ionizing radiation [16], ischemia/reperfusion injury [17], neurodegenerative diseases [18, 19], and chronic pain [9, 11–14]. Some nitroxide radicals, for example, amifostine, are being used in clinical practice [20]. Unlike other antioxidants that act in a sacrificial mode, nitroxide radicals act as self-replenishing antioxidants in a catalytic manner. The TEMPO and α-nitronyl (NIT) groups are the two major kinds of nitroxide radicals (Figure 1). Tempol (4-hydroxy-2,2,6,6-tetramethylpiper-idine-N-oxyl), a kind of TEMPO, is found to alleviate pain in various experimental pain models [12–15, 21]. Compared with Tempol, NIT group nitroxide radicals have an extensive distribution of unpaired spin density. As such, much attention has been levied towards the development of this kind of new NIT nitroxyl radicals. However, whether NIT group NRs possess antinociceptive action has remained elusive.

Bottom Line: However, long-term use of these drugs causes unwanted side effects, which limits their implication.The present study synthesized a novel NIT nitroxide radical with salicylic acid framework (SANR) to provide synergistic effect of both antioxidation and antiinflammation.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neuroscience, Fourth Military Medical University, Xi'an 710032, China.

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.

Show MeSH
Related in: MedlinePlus