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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

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Abstract

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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Acknowledgement

This study was supported by grants from The Department of Science and Technology of Hebei province of China (No.: 98276196D, 04276101D-77).

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Authors and Affiliations

  1. Department of Pathophysiology, Institute of Basic Medicine, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, 050017, People’s Republic of China

    Xiao-Cai Sun, Wei-Na Chen, Shu-Qin Li, Jin-Song Cai, Wen-Bin Li, Xiao-Hui Xian, Yu-Yan Hu, Min Zhang & Qing-Jun Li

  2. Aging and Cognition Neuroscience Laboratory of Hebei Province, 89 Donggang Road, Shijiazhuang, 050031, People’s Republic of China

    Wen-Bin Li

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  1. Xiao-Cai Sun
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Correspondence to Wen-Bin Li.

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X.-C. Sun, W.-N. Chen and S.-Q. Li contributed equally to this work.

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Sun, XC., Chen, WN., Li, SQ. et al. 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. Neurochem Res 34, 351–359 (2009). https://doi.org/10.1007/s11064-008-9785-7

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