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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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Related in: MedlinePlus

Acute treatment of SANR produces antinociceptive effect on CCD-induced mechanical hypersensitivity and thermal hyperalgesia in bilateral hindpaws, which is more potent than parent nitroxide moiety Tempol and parent NSAIDs moiety aspirin. (a, c) Time course of mechanical hypersensitivity (a) and thermal hyperalgesia (c) in ipsilateral hindpaw of CCD rats before and after i.p. SANR (180 μmol/kg) (red) and vehicle treatment (black). Note that ipsilateral mechanical and thermal hyperalgesia was attenuated significantly by SANR. (b, d) Comparison of analgesic potency in ipsilateral mechanical (b) and thermal hyperalgesia (d) produced by the same concentration of SANR, Tempol, and aspirin. Note that SANR showed significantly stronger effect than Tempol and aspirin. (e, g) Contralateral mechanical hypersensitivity (e) and thermal hyperalgesia (g) was reduced by acute SANR as well. (f, h) Comparison of the efficacy by SANR with Tempol and aspirin in inhibiting mechanical (f) and thermal hyperalgesia (h). All data are expressed as mean ± S.E.M. ∗P < 0.05.
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fig5: Acute treatment of SANR produces antinociceptive effect on CCD-induced mechanical hypersensitivity and thermal hyperalgesia in bilateral hindpaws, which is more potent than parent nitroxide moiety Tempol and parent NSAIDs moiety aspirin. (a, c) Time course of mechanical hypersensitivity (a) and thermal hyperalgesia (c) in ipsilateral hindpaw of CCD rats before and after i.p. SANR (180 μmol/kg) (red) and vehicle treatment (black). Note that ipsilateral mechanical and thermal hyperalgesia was attenuated significantly by SANR. (b, d) Comparison of analgesic potency in ipsilateral mechanical (b) and thermal hyperalgesia (d) produced by the same concentration of SANR, Tempol, and aspirin. Note that SANR showed significantly stronger effect than Tempol and aspirin. (e, g) Contralateral mechanical hypersensitivity (e) and thermal hyperalgesia (g) was reduced by acute SANR as well. (f, h) Comparison of the efficacy by SANR with Tempol and aspirin in inhibiting mechanical (f) and thermal hyperalgesia (h). All data are expressed as mean ± S.E.M. ∗P < 0.05.

Mentions: We then further compared the analgesic potency of SANR with the same dosing regimen of traditional nitroxide compound Tempol and classical NSAIDs aspirin alone. As shown in Figure 5(a), SANR at dose of 180 μmol/kg significantly inhibited ipsilateral mechanical hypersensitivity. In contrast, i.p. Tempol and aspirin alone at this low concentration produced little effect on the mechanical hypersensitivity. Quantitative analysis at 7 h after drug delivery revealed that the analgesic potency by SANR was significantly higher than Tempol and aspirin alone (Figure 5(b), P = 0.045 versus Tempol, P = 0.006 versus aspirin). In parallel, SANR exerted stronger inhibition on ipsilateral thermal hyperalgesia when compared to Tempol and aspirin alone (Figures 5(c) and 5(d), n = 10, P = 0.047 versus Tempol, P = 0.025 versus aspirin).


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)

Acute treatment of SANR produces antinociceptive effect on CCD-induced mechanical hypersensitivity and thermal hyperalgesia in bilateral hindpaws, which is more potent than parent nitroxide moiety Tempol and parent NSAIDs moiety aspirin. (a, c) Time course of mechanical hypersensitivity (a) and thermal hyperalgesia (c) in ipsilateral hindpaw of CCD rats before and after i.p. SANR (180 μmol/kg) (red) and vehicle treatment (black). Note that ipsilateral mechanical and thermal hyperalgesia was attenuated significantly by SANR. (b, d) Comparison of analgesic potency in ipsilateral mechanical (b) and thermal hyperalgesia (d) produced by the same concentration of SANR, Tempol, and aspirin. Note that SANR showed significantly stronger effect than Tempol and aspirin. (e, g) Contralateral mechanical hypersensitivity (e) and thermal hyperalgesia (g) was reduced by acute SANR as well. (f, h) Comparison of the efficacy by SANR with Tempol and aspirin in inhibiting mechanical (f) and thermal hyperalgesia (h). All data are expressed as mean ± S.E.M. ∗P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig5: Acute treatment of SANR produces antinociceptive effect on CCD-induced mechanical hypersensitivity and thermal hyperalgesia in bilateral hindpaws, which is more potent than parent nitroxide moiety Tempol and parent NSAIDs moiety aspirin. (a, c) Time course of mechanical hypersensitivity (a) and thermal hyperalgesia (c) in ipsilateral hindpaw of CCD rats before and after i.p. SANR (180 μmol/kg) (red) and vehicle treatment (black). Note that ipsilateral mechanical and thermal hyperalgesia was attenuated significantly by SANR. (b, d) Comparison of analgesic potency in ipsilateral mechanical (b) and thermal hyperalgesia (d) produced by the same concentration of SANR, Tempol, and aspirin. Note that SANR showed significantly stronger effect than Tempol and aspirin. (e, g) Contralateral mechanical hypersensitivity (e) and thermal hyperalgesia (g) was reduced by acute SANR as well. (f, h) Comparison of the efficacy by SANR with Tempol and aspirin in inhibiting mechanical (f) and thermal hyperalgesia (h). All data are expressed as mean ± S.E.M. ∗P < 0.05.
Mentions: We then further compared the analgesic potency of SANR with the same dosing regimen of traditional nitroxide compound Tempol and classical NSAIDs aspirin alone. As shown in Figure 5(a), SANR at dose of 180 μmol/kg significantly inhibited ipsilateral mechanical hypersensitivity. In contrast, i.p. Tempol and aspirin alone at this low concentration produced little effect on the mechanical hypersensitivity. Quantitative analysis at 7 h after drug delivery revealed that the analgesic potency by SANR was significantly higher than Tempol and aspirin alone (Figure 5(b), P = 0.045 versus Tempol, P = 0.006 versus aspirin). In parallel, SANR exerted stronger inhibition on ipsilateral thermal hyperalgesia when compared to Tempol and aspirin alone (Figures 5(c) and 5(d), n = 10, P = 0.047 versus Tempol, P = 0.025 versus aspirin).

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