Current Review of Pain

, Volume 3, Issue 6, pp 432–439 | Cite as

Management of inflammatory pain with selective COX-2 inhibitors: Promises and facts

  • Pedro F. Bejarano
Article

Abstract

The discovery that two cyclooxygenase (COX) isoenzymes, including inducible forms (COX-2), could be selectively inhibited has triggered new research to develop selective inhibitors. During this process, pharmacotherapeutic concepts in inflammatory pain, and clinicians overexpectations, have created some degree of uncertainty for clinicians about the promise of COX-2 inhibitors and the real role they play. The purpose of this article is to critically review, within the context of NSAIDs, some of the old and new concepts in the management of inflammatory pain, as well as to examine the current evidence of the usefulness of COX-2 inhibitors today.

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References and Recommended Reading

  1. 1.
    Vane JR: Inhibition of prostaglandin synthesis as a mechanism for aspirin-like drugs. Nature New Biol 1971, 231:232–235.CrossRefPubMedGoogle Scholar
  2. 2.
    Flower R, Moncada S, Vane JR: Analgesic-antipyretics and anti-inflammatory agents; drugs employed in the treatment of gout. In The Pharmachological Basis of Therapeutics, edn. 6. Edited by Goodman et al. New York: Macmillan; 1981:682–728.Google Scholar
  3. 3.
    De Beaurepaire R, Suaudeau Ch, Chait A, Cimetiére C: Anatomical mapping of brain sites involved in the antinociceptive effects of ketoprofen. Brain Res 1990, 536:201–206.CrossRefPubMedGoogle Scholar
  4. 4.
    McKormack K: The spinal actions of non-steroidal anti-inflammatory drugs and the dissociation between their anti-inflammatory and analgesic effects. Drugs 1994, 47(suppl_5):28–45.CrossRefGoogle Scholar
  5. 5.
    Ferreira S: A classification of peripheral analgesics based upon their mode of action. In Migraine: Spectrum of Ideas. Edited by Sandler M, Collins GM. Oxford: Oxford University Press; 1990:59–72.CrossRefGoogle Scholar
  6. 6.
    Ferreira S: Nitric Oxide analgesia and analgesics [in Spanish]. In Endogenous Nitric Oxide and Nitrovasodilators Drugs. Edited by Berrazueta JR. Santander, Spain: Universidad de Cantabria Publications; 1994:149–162.Google Scholar
  7. 7.
    Kantor T: Selecting the appropiate NSAID. In Drug Therapy. New York: Biomedical Information; 1984 (February issue reprint).Google Scholar
  8. 8.
    Rochon PA, Gurwitz JH, Simms RW, et al.: A study of manufacturer-supported trials of non-steroidal anti-inflammatory drugs in the treatment of Arthritis. Arch Intern Med 1994, 154:157–163.CrossRefPubMedGoogle Scholar
  9. 9.
    Fu JY, Masferrer JL, Seibert K, et al.: The induction and suppression of Prostaglandin H2 synthase (cicloxygenase) in human monocytes. J Biol Chem 1990, 265:16737–16740.PubMedGoogle Scholar
  10. 10.
    Kujubu DA, Fletcher BS, Varnum BC, et al.: TIS10, a phorbol ester tumor promoter-inducible mRNA from swiss 3T3 cells, encodes a novel prostaglandine synthase/cicloxygenase homologue. J Biol Chem 1991, 266:12866–12872.PubMedGoogle Scholar
  11. 11.
    Vane JR, Botting RM: New insights into the mode of action of antiinflammatory drugs. Inflamm Res 1995, 44:1–10.CrossRefPubMedGoogle Scholar
  12. 12.
    Fields H: Peripheral pain sensory system. In Pain. Edited by Fields H. New York: McGraw-Hill; 1987:33.Google Scholar
  13. 13.
    Fields H: Introduction: substances released from primary afferent nociceptors: neurogenic inflammation. In Pain Syndromes in Neurology. Edited by Fields H. London: Butterworths; 1990:4–5.Google Scholar
  14. 14.
    Lotz M, Carson D, Vaughn JH: Substance P activation of rheumatoid synoviocytes: neural pathway in pathogenesis of arthritis. Science 1987, 235:893–895.CrossRefPubMedGoogle Scholar
  15. 15.
    Fries JF, Williams CA, Ramey D, Bloch DA: The relative toxicity of disease-modifying antirheumatic drugs. Arthritis Rheum 1993, 36:297–300.CrossRefPubMedGoogle Scholar
  16. 16.
    Bradley JD, Brandt KD, Katz BP, et al.: Comparison of an antiinflammatory dose of ibuprofen, an analgesic dose of ibuprofen, and acetaminophen in the treatment of patients with osteoarthritis of the knee. N Engl J Med 1991, 325:87–91.CrossRefPubMedGoogle Scholar
  17. 17.
    March L, Irwig L, Schwarz J, et al.: N of 1 trials comparing a non-steroidal anti-inflammatory drug with paracetamol in osteoarthritis. BMJ 1994, 309:1041–1046.CrossRefPubMedCentralPubMedGoogle Scholar
  18. 18.
    Roth SH: Non-steroidal anti-inflammatory drugs: gastropathy, deaths in medical practice [editorial]. Ann Intern Med 1988, 109:353–354.CrossRefPubMedGoogle Scholar
  19. 19.
    Elashoff JD, Grossman MI: Trends in hospital admissions and death rates for peptic ulcer in the United States from 1979 to 1978. Gastroenterology 1980, 78:280–285.PubMedGoogle Scholar
  20. 20.
    Brune K: Spinal cord effects of antipyretic analgesics. Drugs 1994, 47(suppl 5):21–27.CrossRefPubMedGoogle Scholar
  21. 21.
    McCormack K: Non-steroidal anti-inflammatory drugs and spinal processing. Pain 1994, 59:9–43.CrossRefPubMedGoogle Scholar
  22. 22.
    Flynn BL: Rheumatoid arthritis and osteoarthritis: current and future therapies. Am Pharm 1994, NS34:31–37; 41–42.PubMedGoogle Scholar
  23. 23.
    Hawkey CH: COX-2 inhibitors. Lancet 1999, 353:307–314. A very comprehensive review of this new drug class.CrossRefPubMedGoogle Scholar
  24. 24.
    Xie W, Chipman JG, Robertson DL, et al.: Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing. Proc Nat Acad Sci U S A 1991, 88:2692–2696.CrossRefGoogle Scholar
  25. 25.
    O’Banion MK, Sadowski HB, Winn V, et al.: A serum glucocorticoid-regulated 4-Kilobase mRNA encodes a cicloxygenase-related protein. J Biol Chem 1991, 266:23261–23267.PubMedGoogle Scholar
  26. 26.
    Ford-Hutchinson AW: New highly selctive COX-2 inhibitors. In Selective COX-2 Inhibitors: Pharmacology, Clinical Effects and Therapeutical Potential. Edited by Vane J, Botting J. London: William Harvey Press; 1997:117–125.Google Scholar
  27. 27.
    Berde C: COX-2 inhibitors: a status report. IASP Newsletter, Technical Corner. 1998.September/October issue Google Scholar
  28. 28.
    Fu JY, Masferrer JL, Seibert K, et al.: The induction and suppresion of prostaglandin H2 synthase (cicloxygenase) in human monocytes. J Biol Chem 1990, 265:16737–16740.PubMedGoogle Scholar
  29. 29.
    Masferrer JL, Zweifel BS, Seibert S, Needelman P: Selective regulation of cellular cicloxygenase by dexamethasone and endotoxin in mice. J Clin Invest 1990, 86:1375–1379.CrossRefPubMedCentralPubMedGoogle Scholar
  30. 30.
    DeWitt DL: Prostaglandin endoperoxide synthase: regulation of enzyme expression. Biochem Biophys Acta 1991, 1083:121–134.CrossRefPubMedGoogle Scholar
  31. 31.
    Walace JL, Bak A, McKight W, et al.: Cicloxygenase-1 contributes to inflammatory responses in rats end mice: implications for gastrointestinal toxicity. Gastroenterology 1998, 115:101–109.CrossRefGoogle Scholar
  32. 32.
    Goppelt-Struebe, Beiche F: Cicloxygenase-2 in the spinal cord: localization and regulation after a peripheral inflammatory stimulus. Adv Exp Med Biol 1997, 433:213–216.CrossRefPubMedGoogle Scholar
  33. 33.
    Lim H, Paria BC: Multiple female reproductive failures in cicloxygenase deficient mice. Cell 1997, 91:197–208.CrossRefPubMedGoogle Scholar
  34. 34.
    Piret M, Van Ryn J, Mauz A: Differential inhibition of COX-1 and COX-2 by NSAIDs: a summary of results using various test systems. In Selective COX-2 Inhibitors: Pharmachology, Clinical Effects and Therapeuthic Potential, vol 3. Edited by Vane J, Botting J. Dordrecht, The Netherlands: Kluber Academy Publishers; 1997:27–46.Google Scholar
  35. 35.
    Singh G, Rosen-Ramey D: NSAID induced gastrointestinal complications: the ARAMIS perspective. J Rheumatol Suppl 1998, 51:8–16.PubMedGoogle Scholar
  36. 36.
    Patrignani P, Panara MR, Sciulli MG, et al.: Differential inhibition of human prostaglandin endoperoxide-synthase-1 and -2 by non-steroidal anti-inflammatory drugs. J Physiol Pharm 1997, 48:623–631.Google Scholar
  37. 37.
    Lipsky LP, Abramson SB, Crofford L, et al.: The classification of cycloxygenase inhibitors [editorial]. J Rheumatol 1998, 25:2298–2303.PubMedGoogle Scholar
  38. 38.
    Polisson R: Non-steroidal anti-inflammatory drugs: practical and theoretical considerations in their selection. Am J Med 1996, 100(suppl 2A):31–36.CrossRefGoogle Scholar
  39. 39.
    García Rodríguez LA, Jick H: Risk of upper gastrointestinal bleeding and perforation associated with individual non-steroidal anti-inflammatory drugs. Lancet 1994, 343:769–772.CrossRefGoogle Scholar
  40. 40.
    Bjarnason I, McPherson A, Rotman H, et al.: A randomized, double-blind, crossover comparative endoscopy study of the gastroduodenal tolerability of a highly specific cycloxygenase-2 inhibitor flosulide, and naproxen. Scand J Gastroenterol 1997, 32:126–130.CrossRefPubMedGoogle Scholar
  41. 41.
    Rogind H, Bliddal H: Comparison of etodolac and piroxicam in patients with osteoarthritis of the hip or knee. A prospective, randomized, double-blind, controlled multicenter study. Clin Drug Invest 1997, 13:66–75.CrossRefGoogle Scholar
  42. 42.
    Lee S, Lanza F, Lipsky P, et al.: Preliminary study of the safety and efficacy of SC-58635, a novel cycloxygenase-2 inhibitor: efficacy and safety in two placebo-controlled trials in osteoarthritis and rheumatoid arhtritis, and studies of gastrointestinal and platelet effects. Arthritis Rheum 1998, 41:1591–1602.CrossRefGoogle Scholar
  43. 43.
    Lanza Fl, Rack MF, Simon TJ, et al.: Specific inhibition of MK-0966 is associated with less gastroduodenal damage than either aspirin or ibuprofen. Aliment Pharmacol Ther 1999, 13:761–767.CrossRefPubMedGoogle Scholar
  44. 44.
    Engelhart G: Meloxicam: a potent inhibitor of COX-2. In Abstracts of the International Conference on Prostaglandins and Related Compounds. Florence, Italy, June 6–10, 1994;82.Google Scholar
  45. 45.
    Furst DE: Meloxicam: selective COX-2 inhibition in clinical practice. Sem Arthritis Rheum 1997, 26(suppl 6):21–27.CrossRefGoogle Scholar
  46. 46.
    Fenn GC, Morant SV: Safety of meloxicam: a global analysis of clinical trials. Br J Rheum 1997, 36:817–819.CrossRefGoogle Scholar
  47. 47.
    Rainsford KD: Relationship of nimesulide safety to its pharmacokinetics: assessment of adverse reactions. Rheumatology (Oxford) 1999, 38(suppl 1):4–10.CrossRefGoogle Scholar
  48. 48.
    Tannenbaum H, Davis P, Russel A, et al.: An evidence-based approach to prescribing NSAIDs in musculoskeletal disease: a Canadian consensus. CMAJ (Ottawa) 1996, 155:77–88.Google Scholar
  49. 49.
    Catella-Lawson F, McAdam B, Morrison B, et al.: Effects of specific inhibition of cycloxygenase-2 on sodium balance, hemodynamics, and vasoactive eicosanoids. J Pharm Exp Ther 1999, 289:735–741.Google Scholar
  50. 50.
    Bevis PJ, Bird HA, Lapham G, et al.: An open study to assess the safety and tolerability of meloxicam 15 mg in subjects with rheumatic disease and mild renal impairment. Br J Rheumatol 1996, 35(suppl 1):56–60.CrossRefPubMedGoogle Scholar
  51. 51.
    Leone R, Conforti A, Ghiotto E, et al.: Nimesulide and renal impairment. Eur J Clin Pharm 1999, 55:151–154.CrossRefGoogle Scholar
  52. 52.
    Walker A: Quantitative studies of the risk of serious hepatic injury in persons using non-steroidal anti-inflammatory drugs. Arthritis Rheum 1997, 40:201–208.CrossRefPubMedGoogle Scholar
  53. 53.
    García Rodríguez LA, Pérez-Guttman S, Walker AM, et al.: The role of NSAIDs in acute liver injury. BMJ 1992, 305:865–868.CrossRefGoogle Scholar
  54. 54.
    Tolman K: Hepatotoxicity of non-narcotic analgesics. Am J Med 1998, 105(1B):13S-19S.CrossRefPubMedGoogle Scholar
  55. 55.
    Schafer A: Effects of non-steroidal anti-inflammatory therapy on platelets. Am J Med 1999, 106(5B):25S-33S.CrossRefPubMedGoogle Scholar
  56. 56.
    Mengle-Gaw, Hubbard RC, Karim A, et al.: A study of the platelet effects of SC-58635, a novel COX-2 selective inhibitor. Arthritis Rheum 1997, 40(suppl 9):S93.Google Scholar
  57. 57.
    Malmberg AB, Yaksh TL: Antinociceptive actions of spinal non-steroidal anti-inflammatory agents on the formalin test in the rat. J Pharm Exp Ther 1992, 263:136–146.Google Scholar
  58. 58.
    Malmberg AB, Yaksh TL: Hyperalgesia mediated by spinal glutamate or substance P receptor blockade by spinal cicloxigenase inhibition. Science 1992, 257:1276–1279.CrossRefPubMedGoogle Scholar
  59. 59.
    Ballantyne J, Dershwitz M: The pharmacology of non-steroidal antiinflammatory drugs for acute pain. Curr Opin Anesth 1995, 8:461–468.CrossRefGoogle Scholar
  60. 60.
    Woolf C: A new strategy for the treatment of inflammatory pain: prevention or elimination of central sensitization. Drugs 1994, 47(suppl 5):1–9.CrossRefPubMedGoogle Scholar
  61. 61.
    Bejarano PF: Matching analgesic prescription to the pain mechanism [abstract]. In Book of Abstracts, VIIth World Congress on Pain. Seattle: IASP Press; 1993:502.Google Scholar
  62. 62.
    Woolf C, Bennet C, Doherty M, et al.: Towards a mechanismbased classification of pain? Pain 1998, 77:227–229. With reference [61] introduces the hypothesis toward a rational therapeutic approach in pain management.CrossRefPubMedGoogle Scholar
  63. 63.
    Hubbard RC, Geiss GS, Woods EM, et al.: Efficacy, tolerability, and safety of celecoxib, a specific COX-2 inhibitor in osteoarthritis. Rheumatol Eur 1998, 27(suppl 1):118.Google Scholar
  64. 64.
    Saag K, Fisher C, McKay J, et al.: MK-0966 a specific COX-2 inhibitor, has clinical efficacy comparable to ibuprofen in the treatment of knee and hip osteoarthritis (OA) in a six-week controlled clinical trial. Arthritis Rheum 1998, 41(suppl 9):S84.Google Scholar
  65. 65.
    Mehlisch DR, Hubbard RC: The analgesic efficacy and plasma levels of a highly selective inhibitor of COX-2 (SC-58635) in patients with postsurgical dental pain. Clin Pharmacol Ther 1997, 61:195.Google Scholar
  66. 66.
    Erich EW, Dallo B, De Lepeleire, et al.: Characterization of rofecoxib as a cycloxygenase-2 isoform inhibitor and demonstration of analgesia in the dental pain model. Clin Pharmacol Ther 1999, 65:336–347.CrossRefGoogle Scholar
  67. 67.
    Erich D, Mehlisch DR, Perkins S, et al.: Efficacy of MK-966, a highly selective COX-2 inhibitor, in the treatment of postoperative dental pain. Arthritis Rheum 1996, 39(suppl 9):S81.Google Scholar
  68. 68.
    Lipsky P: The clinical potential of cyclooxygenase-2 specific inhibitors. Am J Med 1999, 106(5B):51S-57S. Printed within the proceedings of the most recently published symposium on this topic.CrossRefPubMedGoogle Scholar
  69. 69.
    Kawamori T, Rao TV: Chemopreventive activity of celecoxib, a specific cicloxigenase-2 inhibitor, against colon carcinogenesis. Cancer Res 1998, 58:409–412.PubMedGoogle Scholar

Copyright information

© Current Science Inc 1999

Authors and Affiliations

  • Pedro F. Bejarano
    • 1
  1. 1.Pain Medicine Section, Department of AnesthesiologyFundación Santa Fe de Bogotá, Santafé de BogotáColombia

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