Rapid development of nitric oxide-induced hyperalgesia depends on an alternate to the cGMP-mediated pathway in the rat neuropathic pain model

Inoue, T; Mashimo, Takashi; Shibata, Masahiko; Shibuta, Satoshi; Yoshiya, Ikuto

doi:10.1016/s0006-8993(98)00147-4

Cited by 55 publications

(28 citation statements)

References 52 publications

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“…For example, intrathecal injection of NO donor nitroglycerin induced rapid and transient hyperalgesia in a dose-dependent manner, and accelerated the development and maintenance of hyperalgesia induced by sciatic nerve ligation [1,2]. Moreover, intrathecal administration of NOS inhibitors blocked pain behaviors and hyperalgesia in many pain models at the spinal cord level [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Fluorocitrate, an Inhibitor of Glial Metabolism, Inhibits the Up-Regulation of NOS Expression, Activity and NO Production in the Spinal Cord Induced by Formalin Test in Rats

Sun

Chen

et al. 2008

Neurochem Res

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Previous experiments have suggested that nitric oxide plays an important role in nociceptive transmission in the spinal cord. In order to explore the involvement of glia in the NO-mediated nociceptive transmission, the present study was undertaken to investigate the effect of fluorocitrate (FC), an inhibitor of glial metabolism, on NOS expression and activity and NO production in the spinal cord during the process of peripheral inflammatory pain and hyperalgesia induced by formalin test in rats. Sixty adult male Sprague-Dawley rats were randomly assigned into sham, formalin, formalin + normal saline (NS), and formalin + FC groups. The NOS expression, NOS activity and NO production was detected by NADPH-d histochemistry staining, NOS and NO assay kit, respectively. It was found that formalin test significantly up-regulated NOS expression and activity and NO production in the laminae I-II of the dorsal horn and the grey matter around the central canal in the lumbar spinal cord at 1 h after the formalin test. Selective inhibition of glia metabolism with intrathecal administration of FC (1 nmol) significantly inhibited the up-regulation in NOS expression and activity and NO production normally induced by the formalin test, which was represented with decreases in the number and density of the NADPH-d positive cells in the dorsal horn and grey matter around the central canal, and decrease in density of NADPH-d positive neuropil in the dorsal horn in formalin + FC group compared with formalin group. The results suggested that glia may be involved in the NO-mediated nociceptive transmission in the spinal cord.

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Section: Introductionmentioning

confidence: 99%

Fluorocitrate, an Inhibitor of Glial Metabolism, Inhibits the Up-Regulation of NOS Expression, Activity and NO Production in the Spinal Cord Induced by Formalin Test in Rats

Sun

Chen

et al. 2008

Neurochem Res

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“…This may be due to the decreased NO and cGMP production in diabetic condition as a result of decreased nNOS activity. In contrast, earlier studies have demonstrated that chronic constriction of sciatic nerve causes profound increase of nNOS in the DRG, which could be responsible for hyperalgesia [12].…”

Section: Discussionmentioning

confidence: 76%

Modulatory Effect of the PDE-5 Inhibitor Sildenafil in Diabetic Neuropathy

Patil

Singh

et al. 2004

Pharmacology

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Diabetic neuropathy is one of the most frequent peripheral neuropathies associated with hyperalgesia and hyperesthesia. Besides alteration in the levels of neurotransmitter, alteration in the neuronal nitric oxide synthase (nNOS) is a key factor in the pathogenesis of diabetic neuropathy. The present study was aimed at evaluating the role of PDE-5 inhibitor on nociception in streptozotocin-induced diabetes in animal models of nociception (writhing assay in mice and paw hyperalgesia test in rats). Diabetic animals showed a significant decrease in pain threshold as compared to non-diabetic animals in both tests, indicating diabetes induced hyperalgesia in mice and rats. The PDE-5 inhibitor, sildenafil, significantly increased the pain threshold in both diabetic and non-diabetic animals. However, L-NAME, a non-specific NOS inhibitor and methylene blue (MB), a guanylate cyclase inhibitor blocked the antinociceptive effect. The per se administration of L-NAME or MB augmented the hyperalgesic response in diabetic animals with little or no effect in non-diabetic animals, indicating the alteration of NO-cGMP pathway in diabetes. The results in the present study demonstrate that the decreased nNOS-cGMP system may play a crucial role in the pathogenesis of diabetic neuropathy.

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“…Essas alterações devem ter refletido principalmente as alterações em todo o subcutâneo envolvendo a junta, diferentemente da avaliação do edema apenas das estruturas articulares que efetuamos. A administração intratecal de hemoglobina reduziu a hiperalgesia no modelo da imersão de cauda de ratos (29) e na hiperalgesia térmica (30) . Nós não conseguimos explicar o fato da hemoglobina não ter sido efetiva em reduzir a IA ou a migração celular na artrite por Zy, quando cotejando nossos dados com a literatura, mas diferenças metodológicas certamente estão envolvidas.…”

Section: Discussionunclassified

“…Zy (1mg) foi injetado intra-articularmente (ia) e o IC foi medido na 6 a hora após a indução da artrite no exsudato articular usando câmara de Neubauer. LN (10,30 Figura 4a -Efeito da administração intra-articular de (i.a.) de azul de metileno (AM 500µg/joint) ou hemoglobina (30µmol/junta) sobre a incapacitação articular (IA) na artrite induzida por zymosan (Zy) em ratos.…”

Section: Efeito De Inibidores De Nos No Edema Articular E Naunclassified

Efeito de inibidores da sintase de óxido nítrico na dor inflamatória articular e influxo celular da artrite induzida por zymosan em ratos

Rocha¹,

Rocha²,

Peixoto³

et al. 2003

Rev. Bras. Reumatol.

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Rapid development of nitric oxide-induced hyperalgesia depends on an alternate to the cGMP-mediated pathway in the rat neuropathic pain model

Cited by 55 publications

References 52 publications

Fluorocitrate, an Inhibitor of Glial Metabolism, Inhibits the Up-Regulation of NOS Expression, Activity and NO Production in the Spinal Cord Induced by Formalin Test in Rats

Fluorocitrate, an Inhibitor of Glial Metabolism, Inhibits the Up-Regulation of NOS Expression, Activity and NO Production in the Spinal Cord Induced by Formalin Test in Rats

Modulatory Effect of the PDE-5 Inhibitor Sildenafil in Diabetic Neuropathy

Efeito de inibidores da sintase de óxido nítrico na dor inflamatória articular e influxo celular da artrite induzida por zymosan em ratos

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