The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Preventing Extracellular Diffusion of Trigeminal Nitric Oxide Enhances Formalin-induced Orofacial Pain

  • Jung, Hwi-Seok (School of Dentistry, Brain Korea 21, Brain Science and Engineering Institute, Kyungpook National University) ;
  • Jeon, Hong-Bin (School of Dentistry, Brain Korea 21, Brain Science and Engineering Institute, Kyungpook National University) ;
  • Jeon, Ik-Sung (School of Dentistry, Brain Korea 21, Brain Science and Engineering Institute, Kyungpook National University) ;
  • Lee, Bum-Jun (School of Dentistry, Brain Korea 21, Brain Science and Engineering Institute, Kyungpook National University) ;
  • Yoo, Hyun-Woo (School of Dentistry, Brain Korea 21, Brain Science and Engineering Institute, Kyungpook National University) ;
  • Ahn, Dong-Kuk (Department of Oral Physiology, Brain Korea 21, Brain Science and Engineering Institute, Kyungpook National University) ;
  • Youn, Dong-Ho (Department of Oral Physiology, Brain Korea 21, Brain Science and Engineering Institute, Kyungpook National University)
  • Published : 2009.10.31
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Abstract

Nitric oxide (NO), a diffusible gas, is produced in the central nervous system, including the spinal cord dorsal horn and the trigeminal nucleus, the first central areas processing nociceptive information from periphery. In the spinal cord, it has been demonstrated that NO acts as pronociceptive or antinociceptive mediators, apparently in a concentration-dependent manner. However, the central role of NO in the trigeminal nucleus remains uncertain in support of processing the orofacial nociception. Thus, we here investigated the central role of NO in formalin (3%)-induced orofacial pain in rats by administering membrane-permeable or -impermeable inhibitors, relating to the NO signaling pathways, into intracisternal space. The intracisternal pretreatments with the NO synthase inhibitor L-NAME, the NO-sensitive guanylate cyclase inhibitor ODQ, and the protein kinase C inhibitor GF109203X, all of which are permeable to the cell membrane, significantly reduced the formalin-induced pain, whereas the membrane-impermeable NO scavenger PTIO significantly enhanced it, compared to vehicle controls. These data suggest that an overall effect of NO production in the trigeminal nucleus is pronociceptive, but NO extracellularly diffused out of its producing neurons would have an antinociceptive action.

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References

  1. Bredt DS, Ferris CD, Snyder SH. Nitric oxide synthase regulatory sites. Phosphorylation by cyclic AMP-dependent protein kinase, protein kinase C, and calcium/calmodulin protein kinase; identification of flavin and calmodulin binding sites. J Biol Chem 267: 10976−10981, 1992
  2. Clavelou P, Dallel R, Orliaguet T, Woda A, Raboisson P. The orofacial formalin test in rats: effects of different formalin concentrations. Pain 62: 295−301, 1995 https://doi.org/10.1016/0304-3959(94)00273-H
  3. Dinerman JL, Steiner JP, Dawson TM, Dawson V, Snyder SH. Cyclic nucleotide dependent phosphorylation of neuronal nitric oxide synthase inhibits catalytic activity. Neuropharmacology 33: 1245−1251, 1994 https://doi.org/10.1016/0028-3908(94)90023-X
  4. Ding JD, Weinberg RJ. Localization of soluble guanylyl cyclase in the superficial dorsal horn. J Comp Neurol 495: 668−678, 2006 https://doi.org/10.1002/cne.20901
  5. Duarte ID, Ferreira SH. L-NAME causes antinociception by stimulation of the arginine-NO-cGMP pathway. Mediators Inflamm 9: 25−30, 2000 https://doi.org/10.1080/09629350050024348
  6. Gerber G, Kangrga I, Ryu PD, Larew JS, Randic M. Multiple effects of phorbol esters in the rat spinal dorsal horn. J Neurosci 9: 3606−3617, 1989
  7. Hama AT, Sagen J. Induction of spinal NADPH-diaphorase by nerve injury is attenuated by adrenal medullary transplants. Brain Res 640: 345−351, 1994 https://doi.org/10.1016/0006-8993(94)91892-9
  8. Herdegen T, Rudiger S, Mayer B, Bravo R, Zimmermann M. Expression of nitric oxide synthase and colocalisation with Jun, Fos and Krox transcription factors in spinal cord neurons following noxious stimulation of the rat hindpaw. Brain Res Mol Brain Res 22: 245−258, 1994 https://doi.org/10.1016/0169-328X(94)90053-1
  9. Knowles RG, Palacios M, Palmer RM, Moncada S. Formation of nitric oxide from L-arginine in the central nervous system: a transduction mechanism for stimulation of the soluble guanylate cyclase. Proc Natl Acad Sci U S A 86: 5159−5162, 1989 https://doi.org/10.1073/pnas.86.13.5159
  10. Lin Q, Peng YB, Willis WD. Possible role of protein kinase C in the sensitization of primate spinothalamic tract neurons. J Neurosci 16: 3026−3034, 1996
  11. Meller ST, Gebhart GF. Nitric oxide (NO) and nociceptive processing in the spinal cord. Pain 52: 127−136, 1993 https://doi.org/10.1016/0304-3959(93)90124-8
  12. Nakane M, Mitchell J, Forstermann U, Murad F. Phosphorylation by calcium calmodulin-dependent protein kinase II and protein kinase C modulates the activity of nitric oxide synthase. Biochem Biophys Res Commun 180: 1396−1402, 1991 https://doi.org/10.1016/S0006-291X(05)81351-8
  13. Nakane M, Mitchell J, Forstermann U, Murad F. Phosphorylation by calcium calmodulin-dependent protein kinase II and protein kinase C modulates the activity of nitric oxide synthase. Biochem Biophys Res Commun 180: 1396−1402, 1991 https://doi.org/10.1016/S0006-291X(05)81351-8
  14. Palecek J, Paleckova V, Willis WD. The effect of phorbol esters on spinal cord amino acid concentrations and responsiveness of rats to mechanical and thermal stimuli. Pain 80: 597−605, 1999 https://doi.org/10.1016/S0304-3959(98)00250-4
  15. Ruscheweyh R, Goralczyk A, Wunderbaldinger G, Schober A, Sandkuhler J. Possible sources and sites of action of the nitric oxide involved in synaptic plasticity at spinal lamina I projection neurons. Neuroscience 141: 977−988, 2006 https://doi.org/10.1016/j.neuroscience.2006.04.010
  16. Schmidtko A, Gao W, Konig P, Heine S, Motterlini R, Ruth P, Schlossmann J, Koesling D, Niederberger E, Tegeder I, Friebe A, Geisslinger G. cGMP produced by NO-sensitive guanylyl cyclase essentially contributes to inflammatory and neuropathic pain by using targets different from cGMP-dependent protein kinase I. J Neurosci 28: 8568−8576, 2008 https://doi.org/10.1523/JNEUROSCI.2128-08.2008
  17. Schmidtko A, Tegeder I, Geisslinger G. No NO, no pain? The role of nitric oxide and cGMP in spinal pain processing. Trends Neurosci 32: 339−346, 2009 https://doi.org/10.1016/j.tins.2009.01.010
  18. Semos ML, Headley PM. The role of nitric oxide in spinal nociceptive reflexes in rats with neurogenic and non-neurogenic peripheral inflammation. Neuropharmacology 33: 1487−1497, 1994 https://doi.org/10.1016/0028-3908(94)90053-1
  19. Sluka KA, Willis WD. The effects of G-protein and protein kinase inhibitors on the behavioral responses of rats to intradermal injection of capsaicin. Pain 71: 165−178, 1997 https://doi.org/10.1016/S0304-3959(97)03371-X
  20. Sousa AM, Prado WA. The dual effect of a nitric oxide donor in nociception. Brain Res 897: 9−19, 2001 https://doi.org/10.1016/S0006-8993(01)01995-3
  21. Tegeder I, Schmidtko A, Niederberger E, Ruth P, Geisslinger G. Dual effects of spinally delivered 8-bromo-cyclic guanosine mono- phosphate (8-bromo-cGMP) in formalin-induced nociception in rats. Neurosci Lett 332: 146−150, 2002 https://doi.org/10.1016/S0304-3940(02)00938-2
  22. Valtschanoff JG, Weinberg RJ, Rustioni A, Schmidt HH. Nitric oxide synthase and GABA colocalize in lamina II of rat spinal cord. Neurosci Lett 148: 6−10, 1992 https://doi.org/10.1016/0304-3940(92)90791-5
  23. Yashpal K, Pitcher GM, Parent A, Quirion R, Coderre TJ. Noxious thermal and chemical stimulation induce increases in 3H- phorbol 12,13-dibutyrate binding in spinal cord dorsal horn as well as persistent pain and hyperalgesia, which is reduced by inhibition of protein kinase C. J Neurosci 15: 3263−3272, 1995
  24. Yeo JF. Does nitric oxide play a role in orofacial pain transmission? Ann N Y Acad Sci 962: 151−160, 2002 https://doi.org/10.1111/j.1749-6632.2002.tb04065.x
  25. Yeo JF, Tang FR, Leong SK. Ultrastructural study of NADPH-d positive neurons in laminae I and II of the rat caudal spinal trigeminal nucleus. Int J Neurosci 91: 29−43, 1997 https://doi.org/10.3109/00207459708986363

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