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Effects of NOS Inhibitors on Arthritis and Arthritic Pain in Rats  

Min, Sun-Seek (Department of Physiology and Biophysics, College of Medicine, Eulji University)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.11, no.6, 2007 , pp. 253-257 More about this Journal
Abstract
Among the arthritis symptoms, chronic pain is the most serious, and it can profoundly affect the quality of human life. Unfortunately, the mechanism of development in arthritis and arthritic pain has not yet been precisely elucidated. Accumulating evidence indicates that nitric oxide (NO) plays a pivotal role in nociceptive processing in the spinal cord. However, the modulation mechanism of NO in the peripheral site of arthritis and arthritic pain has not been clarified. Therefore, I determined in the present study which nitric oxide synthase (NOS) was involved in the induction of arthritis and arthritic pain. Monoarthritis was induced by intra-articular injection of carrageenan (2%, $50{\mu}l$) into rats, and resulted in the reduction of weight load on the injected leg, increase of knee joint diameter and inflammatory response. Pre-treatment of rats with L-N6-(1-iminoethyl)-lysine (L-NIL, $500{\mu}g$, in $50{\mu}l$), an inhibitor of inducible NOS (iNOS), partially prevented the induction of pain-related behavior and partially reduced inflammatory response in the synovial membrane in the knee joint. These results suggest that iNOS in the knee joint may play an important role in the induction of pain-related behavior and inflammation, and that NO produced by iNOS may be associated with nociceptive signaling in the peripheral site.
Keywords
Nitric oxide (NO); Arthritis; Arthritic pain; Nitric oxide syntase (NOS);
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1 Honore P, Chapman V, Buritova J, Besson JM. Reduction of carrageenin oedema and the associated c-Fos expression in the rat lumbar spinal cord by nitric oxide synthase inhibitor. Br J Pharmacol 114: 77-84, 1995
2 Ialenti A, Moncada S, Di Rosa M. Modulation of adjuvant arthritis by endogenous nitric oxide. Br J Pharmacol 110: 701-706, 1993
3 Moncada S, Palmar RMJ, Higgs EA. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327: 524-526, 1991
4 Yang LC, Masala M, Yaksh TL. Characterization of time course of spinal cord amino acids, citrulline adn PGE2 release after carrageenan/kaolin-induced knee joint inflammation : a chronic microdialysis study. Pain 67: 345-354, 1996
5 Chu YC, Guan Y, Skinner J, Raja SN, Johns RA, Tao YX. Effect of genetic knockout or pharmacologic inhibition of neuronal nitric oxide synthase on complete Freund's adjuvant-induced persistent pain. Pain 119: 113-123, 2005   DOI   PUBMED   ScienceOn
6 Cannon GW, Openshaw SJ, Hibbs JBJ, Hoidal JR, Huecksteadt TP, Griffiths MM. Nitric oxide production during adjuvantinduced and collagen-induced arthritis. Arthritis Rheum 39: 1677-1684, 1996
7 Bredt DS, Snyder SH. Nitric oxide, a novel neuronal messenger. Neuron 8: 3-11, 1992
8 Stadler JM, Stefanovic-Racic, Billiar TR, Curran RD, McIntyre LA,Georgescu HI, Simmons RL, Evans CH. Articular chondrocytes synthesize nitric oxide in response to cytokines and lipopolysaccharide. J Immunol 147: 3915-3920, 1991
9 Connor JR, Manning PT, Settle SL, Moore WM, Jerome GM, Webber RK, Tjoeng FS, Currie MG. Suppression of adjuvantinduced arthritis by selective inhibition of inducible nitric oxide synthase. Eur J Pharmacol 273: 15-24, 1995
10 Holthusen H, Arndt JO. Nitric oxide evokes pain in humans on intracutaneous injection. Neurosci Lett 165: 71-74, 1994
11 Moncada S, Palmar RMJ, Higgs EA. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327, 524-526, 1991
12 Min SS, Han JS, Kim YI, Na HS, Yoon YW, Hong SK, Han HC. A novel method for convenient assessment of arthritic pain in voluntarily walking rats. Neurosci Lett 308: 95-98, 2001
13 Palmer RMJ, Hickery MS, Charles IG, Moncada S, Bayliss MT. Induction of nitric oxide synthase in human chondrocytes. Biochem Biophys Res Commun 193: 398-405, 1993
14 Zimmermann M. Pathobiology of neuropathic pain. Eur J Pharmacol 429: 23-37, 2001   DOI   PUBMED   ScienceOn
15 Infante C, Díaz M, Hernández A, Constandil L, Pelissier T. Expression of nitric oxide synthase isoforms in the dorsal horn of monoarthritic rats: effects of competitive and uncompetitive N-methyl-D-aspartate antagonists. Arthritis Res Ther 9: R53, 2007   DOI   ScienceOn
16 Langrehr JM, Murase N, Markus PM, Cai X, Neuhaus P, Schraut W, Simmons RL, Hoffman RA. Nitric oxide production in hist-versus-graft and graft-versus-host reactions in the rat. J Clin Invest 90: 679-683, 1992
17 Murphy S. Production of nitric oxide by glial cells. Glia 29: 1-13, 2000
18 Corbett JA, Lancaster JR, Sweetland Jr MA, McDaniel ML. Interleukin-1$\beta$-induced formation of EPR-detectable iron-nitrosyl complexes in islets of Langerhans. J Biol Chem 266: 21351- 21354, 1991
19 Lawand NB, Willis WD, Westlund KN. Blockade of joint inflammation and secondary hyperalgesia by L-NAME, a nitric oxide synthase inhibitor. Neuro Report 8: 895-899, 1997
20 Charles IG, Palmer RMJ, Hickery MS, Bayliss MT, Chubb AP, Hall VS, Moss DW, Moncada S. Cloning, characterization and expression of a cDNA encoding an inducible nitric oxide synthase from the human chondrocyte. Proc Natl Acad Sci 90: 11419-11423, 1993
21 Kolb H, Kiesel U, Kroncke KD, Kolb-Bachofen V. Suppression of low dose streptozotocin induced diabetes in mice by administration of a nitric oxide synthase inhibitor. Life Sci 49: 213- 217, 1991
22 Zheng YM, Schafer MKH, Weihe E, Sheng H, Corisdco S, Fu ZF, Koprowski H, Dietzschold B. Severity of neurological signs and degree of inflammatory lesions in the brains of rats with borna disease correlate with the induction of nitric oxide synthase. J Virol 67: 5786-5789, 1993
23 Laurido C, Hernández A, Constandil L, Pelissier T. Nitric oxide synthase and soluble guanylate cyclase are involved in spinal cord wind-up activity of monoarthritic, but not of normal rats. Neurosci Lett 352: 64-66, 2003   DOI   ScienceOn
24 Corbett JA, Lancaster JR, Sweetland Jr MA, McDaniel ML. Interleukin-1$\beta$-induced formation of EPR-detectable iron-nitrosyl complexes in islets of Langerhans. J Biol Chem 266: 21351- 21354, 1991
25 Moore PK, Wallace P, Gaffen Z, Hart SL, Babbedge RC. Characterization of the novel nitric oxide synthase inhibitor 7-nitro indazole and related indazoles: antinociceptive and cardiovascular effects. Br J Pharmacol 110: 219-224, 1993
26 Farrell AJ, Blake DR, Palmer RMJ, Moncada S. Increased concentrations of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases. Ann Rheum Dis 51: 1219-1222, 1992
27 Stefanovic-Racic M, Mayers K, Meschter C, Coffey JW, Hoffman RA, Evans CH. N-monomethyl arginine, an inhibitor of nitric oxide synthase, suppresses the development of adjuvant arthritis in rats. Arthritis Rheum 37: 1062-1069, 1994
28 Meller ST, Cumming CP, Traub RJ, Gebhart GF. The role of nitric oxide in the development and maintenance of the hyperalgesia produced by intraplantar injection of carrageenan in the rat. Neuroscience 60: 367-374, 1994