The Journal of Pain
Volume 10, Issue 1 , Pages 80-89 , January 2009

Variants of Neural Nitric Oxide Synthase in the Spinal Cord of Neuropathic Rats and Their Effects on Nuclear Factor-κB (NF-κB) Activity in PC12 Cells

  • Xiao-Gao Jin

      Affiliations

    • Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
    • ,
  • Song-Qing He

      Affiliations

    • Department of Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
    • ,
  • Xue-Tao Yan

      Affiliations

    • Department of Anesthesiology, Taihe Hospital, Yunyang Medical College, Shiyan, Hubei Province, China
    • ,
  • Guangxiong Zhang

      Affiliations

    • Department of Anesthesiology, Hubei Provincial Corps Hospital, Chinese People's Armed Police Forces, Wuhan, Hubei Province, China
    • ,
  • Li Wan

      Affiliations

    • Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
    • ,
  • Jintao Wang

      Affiliations

    • Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
    • ,
  • Yawen Li

      Affiliations

    • Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
    • ,
  • Xuebi Tian

      Affiliations

    • Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
    • ,
  • Yuke Tian

      Affiliations

    • Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
    • ,
  • Ailin Luo

      Affiliations

    • Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
    • Corresponding Author InformationAddress reprint requests to Dr. Ailin Luo, Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China

Received 4 March 2008 ,Revised 13 July 2008 ,Accepted 22 July 2008.

References 

  1. Aarts M, Liu Y, Liu L, Besshoh S, Arundine M, Gurd JW, et al. Treatment of ischemic brain damage by perturbing NMDA receptor-PSD-95 protein interactions. Science. 2002;298:846–850
  2. Alderton WK, Cooper CE, Knowles RG. Nitric oxide synthases: Structure, function and inhibition. Biochem J. 2001;357:593–615
  3. Arruda JL, Sweitzer S, Rutkowski MD, DeLeo JA. Intrathecal anti-IL-6 antibody and IgG attenuates peripheral nerve injury-induced mechanical allodynia in the rat: Possible immune modulation in neuropathic pain. Brain Res. 2000;879:216–225
  4. Bridges D, Thompson SW, Rice AS. Mechanisms of neuropathic pain. Br J Anaesth. 2001;87:12–26
  5. Chen SR, Khan GM, Pan HL. Antiallodynic effect of intrathecal neostigmine is mediated by spinal nitric oxide in a rat model of diabetic neuropathic pain. Anesthesiology. 2001;95:1007–1012
  6. Chen SR, Pan HL. Spinal nitric oxide contributes to the analgesic effect of intrathecal [d-pen2, d-pen5]-enkephalin in normal and diabetic rats. Anesthesiology. 2003;98:217–222
  7. Christopherson KS, Hillier BJ, Lim WA, Bredt DS. PSD-95 assembles a ternary complex with the N-methyl-D-aspartic acid receptor and a bivalent neuronal NO synthase PDZ domain. J Biol Chem. 1999;274:27467–27473
  8. Cizkova D, Lukacova N, Marsala M, Marsala J. Neuropathic pain is associated with alterations of nitric oxide synthase immunoreactivity and catalytic activity in dorsal root ganglia and spinal dorsal horn. Brain Res Bull. 2002;58:161–171
  9. Cui H, Hayashi A, Sun HS, Belmares MP, Cobey C, Phan T, et al. PDZ protein interactions underlying NMDA receptor-mediated excitotoxicity and neuroprotection by PSD-95 inhibitors. J Neurosci. 2007;7:9901–9915
  10. Decosterd I, Woolf CJ. Spared nerve injury: An animal model of persistent peripheral neuropathic pain. Pain. 2000;87:149–158
  11. Eliasson MJ, Blackshaw S, Schell MJ, Snyder SH. Neuronal nitric oxide synthase alternatively spliced forms: Prominent functional localizations in the brain. Proc Natl Acad Sci U S A. 1997;94:3396–3401
  12. Gordh T, Sharma HS, Alm P, Westman J. Spinal nerve lesion induces upregulation of neuronal nitric oxide synthase in the spinal cord: An immunohistochemical investigation in the rat. Amino Acids. 1998;14:105–112
  13. Guan Y, Yaster M, Raja SN, Tao YX. Genetic knockout and pharmacologic inhibition of neuronal nitric oxide synthase attenuate nerve injury-induced mechanical hypersensitivity in mice. Mol Pain. 2007;3:29
  14. Huber A, Saur D, Kurjak M, Schusdziarra V, Allescher HD. Characterization and splice variants of neuronal nitric oxide synthase in rat small intestine. Am J Physiol. 1998;275:G1146–G1156
  15. Iwamoto ET, Marion L. Pharmacologic evidence that spinal muscarinic analgesia is mediated by an L-arginine/nitric oxide/cyclic GMP cascade in rats. J Pharmacol Exp Ther. 1994;271:601–608
  16. Kawamata T, Omote K. Activation of spinal N-methyl-D-aspartate receptors stimulates a nitric oxide/cyclic guanosine 3,5-monophosphate/glutamate release cascade in nociceptive signaling. Anesthesiology. 1999;91:1415–1424
  17. Kennedy MB. The postsynaptic density at glutamatergic synapses. Trends Neurosci. 1997;20:264–268
  18. Khan GM, Li DP, Chen SR, Pan HL. Role of spinal nitric oxide in the inhibitory effect of [D-Pen2,D-Pen5]-enkephalin on ascending dorsal horn neurons in normal and diabetic rats. J Pharmacol Exp Ther. 2002;303:1021–1028
  19. Kone BC, Kuncewicz T, Zhang W, Yu ZY. Protein interactions with nitric oxide synthases: Controlling the right time, the right place, and the right amount of nitric oxide. Am J Physiol Renal Physiol. 2003;285:F178–F190
  20. Lee MA, Cai L, Hübner N, Lee YA, Lindpaintner K. Tissue- and development-specific expression of multiple alternatively spliced transcripts of rat neuronal nitric oxide synthase. J Clin Invest. 1997;100:1507–1512
  21. Lui PW, Lee CH. Preemptive effects of intrathecal cyclooxygenase inhibitor or nitric oxide synthase inhibitor on thermal hypersensitivity following peripheral nerve injury. Life Sci. 2004;75:2527–2538
  22. Ma W, Bisby MA. Increased activation of nuclear factor kappa B in rat lumbar dorsal root ganglion neurons following partial sciatic nerve injuries. Brain Res. 1998;797:243–254
  23. Mabuchi T, Matsumura S, Okuda-Ashitaka E, Kitano T, Kojima H, Nagano T, et al. Attenuation of neuropathic pain by the nociceptin/orphanin FQ antagonist JTC-801 is mediated by inhibition of nitric oxide production. Eur J Neurosci. 2003;17:1384–1392
  24. Martucci C, Trovato AE, Costa B, Borsani E, Franchi S, Magnaghi V, et al. The purinergic antagonist PPADS reduces pain related behaviours and interleukin-1beta, interleukin-6, iNOS and nNOS overproduction in central and peripheral nervous system after peripheral neuropathy in mice. Pain. 2008;137:81–95
  25. Masue T, Dohi S, Asano T, Shimonaka H. Spinal antinociceptive effect of epidural nonsteroidal antiinflammatory drugs on nitric oxide-induced hyperalgesia in rats. Anesthesiology. 1999;91:198–206
  26. Naik AK, Tandan SK, Kumar D, Dudhgaonkar SP. Nitric oxide and its modulators in chronic constriction injury-induced neuropathic pain in rats. Eur J Pharmacol. 2006;530:59–69
  27. Ogura T, Yokoyama T, Fujisawa H, Kurashima Y, Esumi H. Structural diversity of neuronal nitric oxide synthase mRNA in the nervous system. Biochem Biophys Res Commun. 1993;193:1014–1022
  28. O'Rielly DD, Loomis CW. Increased expression of cyclooxygenase and nitric oxide isoforms, and exaggerated sensitivity to prostaglandin E2, in the rat lumbar spinal cord 3 days after L5-L6 spinal nerve ligation. Anesthesiology. 2006;104:328–337
  29. Pan HL, Chen SR, Eisenach JC. Role of spinal NO in antiallodynic effect of intrathecal clonidine in neuropathic rats. Anesthesiology. 1998;89:1518–1523
  30. Sattler R, Xiong Z, Lu WY, Hafner M, MacDonald JF, Tymianski M. Specific coupling of NMDA receptor activation to nitric oxide neurotoxicity by PSD-95 protein. Science. 1999;284:1845–1848
  31. Saur D, Neuhuber WL, Gengenbach B, Huber A, Schusdziarra V, Allescher HD. Site-specific gene expression of nNOS variants in distinct functional regions of rat gastrointestinal tract. Am J Physiol Gastrointest Liver Physiol. 2002;282:G349–G358
  32. Song HK, Pan HL, Eisenach JC. Spinal nitric oxide mediates antinociception from intravenous morphine. Anesthesiology. 1998;89:215–221
  33. Stefano GB, Goumon Y, Bilfinger TV, Welters ID, Cadet P. Basal nitric oxide limits immune, nervous and cardiovascular excitation: Human endothelia express a mu opiate receptor. Prog Neurobiol. 2000;60:513–530
  34. Sun T, Song WG, Fu ZJ, Liu ZH, Liu YM, Yao SL. Alleviation of neuropathic pain by intrathecal injection of antisense oligonucleotides to p65 subunit of NF-kappaB. Br J Anaesth. 2006;97:553–558
  35. Tegeder I, Niederberger E, Schmidt R, Kunz S, Guhring H, Ritzeler O, et al. Specific Inhibition of IkappaB kinase reduces hyperalgesia in inflammatory and neuropathic pain models in rats. J Neurosci. 2004;24:1637–1645
  36. Welters ID, Menzebach A, Goumon Y, Cadet P, Menges T, Hughes TK, et al. Morphine inhibits NF-kappaB nuclear binding in human neutrophils and monocytes by a nitric oxide-dependent mechanism. Anesthesiology. 2000;92:1677–1684
  37. Wu WP, Hao JX, Ongini E, Impagnatiello F, Presotto C, Wiesenfeld-Hallin Z, et al. A nitric oxide (NO)-releasing derivative of gabapentin, NCX 8001, alleviates neuropathic pain-like behavior after spinal cord and peripheral nerve injury. Br J Pharmacol. 2004;141:65–74
  38. Xu L, Mabuchi T, Katano T, Matsumura S, Okuda-Ashitaka E, Sakimura K, et al. Nitric oxide (NO) serves as a retrograde messenger to activate neuronal NO synthase in the spinal cord via NMDA receptors. Nitric Oxide. 2007;17:18–24
  39. Xu Z, Chen SR, Eisenach J, Pan HL. Role of spinal muscarinic and nicotinic receptors in clonidine-induced nitric oxide release in a rat model of neuropathic pain. Brain Res. 2000;861:390–398
  40. Zimmermann M. Ethical guidelines for investigation of experimental pain in conscious animals. Pain. 1983;16:109–110

PII: S1526-5900(08)00688-3

doi: 10.1016/j.jpain.2008.07.009

The Journal of Pain
Volume 10, Issue 1 , Pages 80-89 , January 2009

Article Tools

* Image Usage & Resolution