The Korean Journal of Pain

  • 제19권1호
  • /
  • Pages.17-21
  • /
  • 2006
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  • 2005-9159(pISSN)
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  • 2093-0569(eISSN)
대한통증학회 (The Korean Pain Society)
권호 표지

쥐를 이용한 포르말린 및 열 유발 통증에서 척수강 Sildenafil의 효과에 관한 연구

Evaluation for the Effects of Intrathecal Sildenafil on the Formalin- and Thermal-induced Nocieption of Rats

  • 윤명하 (전남대학교 의과대학 마취통증의학교실) ;
  • 배홍범 (전남대학교 의과대학 마취통증의학교실) ;
  • 신동진 (전남대학교 의과대학 마취통증의학교실) ;
  • 김창모 (전남대학교 의과대학 마취통증의학교실) ;
  • 정성태 (전남대학교 의과대학 마취통증의학교실) ;
  • 김석재 (전남대학교 의과대학 마취통증의학교실) ;
  • 최정일 (전남대학교 의과대학 마취통증의학교실)
  • Yoon, Myung Ha (Department of Anesthesiology and Pain Medicine, Medical School, Chonnam National University) ;
  • Bae, Hong Buem (Department of Anesthesiology and Pain Medicine, Medical School, Chonnam National University) ;
  • Shin, Dong Jin (Department of Anesthesiology and Pain Medicine, Medical School, Chonnam National University) ;
  • Kim, Chang Mo (Department of Anesthesiology and Pain Medicine, Medical School, Chonnam National University) ;
  • Jeong, Sung Tae (Department of Anesthesiology and Pain Medicine, Medical School, Chonnam National University) ;
  • Kim, Seok Jai (Department of Anesthesiology and Pain Medicine, Medical School, Chonnam National University) ;
  • Choi, Jeong Il (Department of Anesthesiology and Pain Medicine, Medical School, Chonnam National University)
  • 투고 : 2005.03.31
  • 심사 : 2005.07.07
  • 발행 : 2006.06.30
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초록

Background: Cyclic guanosine monophosphate (cGMP) plays an important role in the modulation of nociception. Although local sildenafil produces antinociception, by increasing cGMP through the inhibition of phosphodiesterase 5, the effect of spinal sildenafil has not been determined. The authors evaluated the effects of intrathecal sildenafil on the nociceptive behavior evoked by formalin injection and thermal stimulation. Methods: Lumbar intrathecal catheters were implanted into rats, with formalin and Hot-Box tests used as nociceptive models. The formalin-induced nociceptive behavior (flinching response) and withdrawal latency to radiant heat were measured, and the general behaviors also observed. Results: The intrathecal administration of sildenafil produced dose-dependent suppression of the flinches in both phases in the formalin test, and increased the withdrawal latency in the Hot-Box test. No abnormal behaviors were noted. Conclusions: Sildenafil, an inhibitor of phosphodiesterase 5, is active against the nociceptive state evoked in the spinal cord by formalin and thermal stimulations. Accordingly, spinal sildenafil may be useful in the management of pain.

키워드

과제정보

연구 과제 주관 기관 : 전남대학교병원

참고문헌

  1. Beavo JA, Reifsnyder DH: Primary sequence of cyclic nucleotide phosphodiesterase isozymes and the design of selective inhibitors. Trends Pharmacol Sci 1990; 11: 150-5 https://doi.org/10.1016/0165-6147(90)90066-H
  2. Moreland RB, Goldstein II, Kim NN, Traish A: Sildenafil citrate, a selective phosphodiesterase type 5 inhibitor. Trends Endoctinol Metab 1999; 10: 97-104 https://doi.org/10.1016/S1043-2760(98)00127-1
  3. Pyne NJ, Atshavsky V, Lochhead A: cGMP signal termination. Biochem Soc Trans 1996; 24: 1019-22 https://doi.org/10.1042/bst0241019
  4. Moncada S, Higgs A: The L-arginine-nitric oxide pathway. N Engl J Med 1993; 329: 2002-12 https://doi.org/10.1056/NEJM199312303292706
  5. Nathan C: Inducible nitric oxide synthase: what diffetence does it make? J Clin Invest 1997; 100: 2417-23 https://doi.org/10.1172/JCI119782
  6. Mixcoatl-Zecuatl T, Aguirre-Banuelos P, Granados-Soto V: Sildenafil ptoduces antinockeption and increases morphine antinociception in the formalin test. Eur J Pharmacol 2000; 400: 81-7 https://doi.org/10.1016/S0014-2999(00)00361-7
  7. Jain NK, Patil CS, Singh A, Kulkarni SK: Sildenafil-induced peripheral analgesia and activation of the nitric oxide-cyclic GMP pathway. Brain Res 2001; 909: 170-8 https://doi.org/10.1016/S0006-8993(01)02673-7
  8. Asomoza-Espinosa R, Alonso-Lopez R, Mixcoatl-Zecuatl T, Aguirre-Banuelos P, Torres-Lopez JE, Granados-Soto V: Sildenafil incteases diclofenac antinociception in the formalin test. Eur J Pharmacol 2001; 418: 195-200 https://doi.org/10.1016/S0014-2999(01)00956-6
  9. Jain NK, Patil CS, Singh A, Kulkarni SK: Sildenafil, a phospho-diestetase-5 inhibitor, enhances the antinociceptive effect of morphine. Pharmacology 2003; 67: 150-6 https://doi.org/10.1159/000067802
  10. Patil CS, Jain NK, Singh A, Kulkarm SK: Modulatory effect of cyclooxygenase inhibitors on sildenafil-induced antinociception. Pharmacology 2003; 69: 183-9 https://doi.org/10.1159/000073662
  11. Terrert NK, Bell AS, Brown D, Ellis P: Sildenafil ($Vigra^{TM}$) a potent and selective inhibitor of type 5 cGMP phosphodiesterase with utility for the treatment of male erectile dysfunction. Bioorg Med Chem Lett 1996; 6: 1819-24 https://doi.org/10.1016/0960-894X(96)00323-X
  12. Boolell M, Gepi-Attee S, Gingell JC, Allen MJ: Sildenafil, a novel effective oral therapy for male erectile dysfunction. Br J Urol 1996; 78: 257-61 https://doi.org/10.1046/j.1464-410X.1996.10220.x
  13. Yoon MH, Choi JI, Kwak SH: Characteristic of interactions berween intrathecal gabapentin and either clonidine or neostigmine in the formalin test. Anesth Analg 2004; 98: 1374-9
  14. Yoon MH, Yaksh TL: The effect of intrathecal gabapentin on pain behavior and hemodynamic on rhe formalin rest in the rat. Anesth Analg 1999; 89: 434-9 https://doi.org/10.1097/00000539-199908000-00034
  15. Yaksh TL, Rudy TA: Chronic catheterization of the spinal subarachnoid space. Physiol Behav 1976; 17: 1031-6 https://doi.org/10.1016/0031-9384(76)90029-9
  16. Tallarida RJ, Murray RB: Manual of pharmacologic calculations with computer programs. 2nd ed. New York, Springer-Verlag. 1987, pp 1-95
  17. Wilcox GL, Seybold V: Pharmacology of spinal afferent processing. In: Anesthesia: Biologic foundations. Edited by Yaksh TL, Lynch III C, Zapol WM, Maze M, Biebuyck JF, Saidman LJ: Philadelphia, Lippincott-Raven Publishers. 1997, pp 557-76
  18. Stacey P, Rulten S, Dapling A, Phillips SC: Molecular cloning and expression of human cGMP-binding cGMP-specific phosphodiesterase (PDE5). Biochem Biophys Res Commun 1998; 247: 249-54 https://doi.org/10.1006/bbrc.1998.8769
  19. Pyne NJ, Arshavsky V, Lochhead A: cGMP signal termination. Biochem Soc Trans 1996; 24: 1019-22 https://doi.org/10.1042/bst0241019
  20. Beavo JA: Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms. Physiol Rev 1995; 75: 725-48 https://doi.org/10.1152/physrev.1995.75.4.725