Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1992 Feb;105(2):412–416. doi: 10.1111/j.1476-5381.1992.tb14267.x

Effects of systemic non-steroidal anti-inflammatory drugs on nociception during tail ischaemia and on reperfusion hyperalgesia in rats.

L Gelgor 1, N Butkow 1, D Mitchell 1
PMCID: PMC1908643  PMID: 1559131

Abstract

1. We have investigated the effects of five non-steroidal anti-inflammatory drugs (NSAIDs) on nociception during ischaemia and on reperfusion hyperalgesia in rats. 2. We induced tail ischaemia in conscious rats by applying a tourniquet at the base of the tail until the rats exhibited co-ordinated escape behaviour when we released the tourniquet. 3. We assessed hyperalgesia by measuring the tail flick latency following tail immersion in water at 49 degrees C, before applying and immediately after releasing the tourniquet, and then at 30 min intervals for 2 h. 4. Intraperitoneal injection of NSAIDs prior to applying the tourniquet had no effect on the co-ordinated escape behaviour during ischaemia, nor on tail flick latency in the absence of prior ischaemia. However all the drugs attenuated reperfusion hyperalgesia in a log dose-dependent manner. Doses required to abolish hyperalgesia, were indomethacin 5 mg kg-1, diclofenac sodium 42 mg kg-1, ibuprofen 54 mg kg-1, dipyrone 168 mg kg-1 and paracetamol 170 mg kg-1. 5. We conclude that the mechanisms underlying nociception during ischaemia are not the same as those underlying reperfusion hyperalgesia. Moreover our procedure provides a rapid and more humane method for measuring the antinociceptive potency of NSAIDs.

Full text

PDF
415

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berge O. G., Garcia-Cabrera I., Hole K. Response latencies in the tail-flick test depend on tail skin temperature. Neurosci Lett. 1988 Apr 12;86(3):284–288. doi: 10.1016/0304-3940(88)90497-1. [DOI] [PubMed] [Google Scholar]
  2. Carlsson K. H., Helmreich J., Jurna I. Activation of inhibition from the periaqueductal grey matter mediates central analgesic effect of metamizol (dipyrone). Pain. 1986 Dec;27(3):373–390. doi: 10.1016/0304-3959(86)90161-2. [DOI] [PubMed] [Google Scholar]
  3. Ethical standards for investigations of experimental pain in animals. The Committee for Research and Ethical Issues of the International Association for the Study of Pain. Pain. 1980 Oct;9(2):141–143. doi: 10.1016/0304-3959(80)90002-0. [DOI] [PubMed] [Google Scholar]
  4. Ferreira S. H., Lorenzetti B. B., Corrêa F. M. Central and peripheral antialgesic action of aspirin-like drugs. Eur J Pharmacol. 1978 Dec 15;53(1):39–48. doi: 10.1016/0014-2999(78)90265-0. [DOI] [PubMed] [Google Scholar]
  5. Flower R. J., Vane J. R. Inhibition of prostaglandin synthetase in brain explains the anti-pyretic activity of paracetamol (4-acetamidophenol). Nature. 1972 Dec 15;240(5381):410–411. doi: 10.1038/240410a0. [DOI] [PubMed] [Google Scholar]
  6. Flower R., Gryglewski R., Herbaczyńska-Cedro K., Vane J. R. Effects of anti-inflammatory drugs on prostaglandin biosynthesis. Nat New Biol. 1972 Jul 26;238(82):104–106. doi: 10.1038/newbio238104a0. [DOI] [PubMed] [Google Scholar]
  7. Gelgor L., Phillips S., Butkow N., Mitchell D. Injectable aspirin and mepyramine abolish post-ischaemic hyperalgesia in rats. Pain. 1986 Sep;26(3):353–359. doi: 10.1016/0304-3959(86)90063-1. [DOI] [PubMed] [Google Scholar]
  8. Gelgor L., Phillips S., Mitchell D. Hyperalgesia following ischaemia of the rat's tail. Pain. 1986 Feb;24(2):251–257. doi: 10.1016/0304-3959(86)90047-3. [DOI] [PubMed] [Google Scholar]
  9. Han J. S., Ren M. F. The importance of monitoring tail-skin temperature in measuring tail-flick latency. Pain. 1991 Jul;46(1):117–117. doi: 10.1016/0304-3959(91)90043-W. [DOI] [PubMed] [Google Scholar]
  10. Juan H. Dependence of histamine-evoked nociception on prostaglandin release. Agents Actions. 1981 Dec;11(6-7):706–710. doi: 10.1007/BF01978793. [DOI] [PubMed] [Google Scholar]
  11. Juan H. Prostaglandins as modulators of pain. Gen Pharmacol. 1978;9(6):403–409. doi: 10.1016/0306-3623(78)90025-3. [DOI] [PubMed] [Google Scholar]
  12. Jurna I., Brune K. Central effect of the non-steroid anti-inflammatory agents, indomethacin, ibuprofen, and diclofenac, determined in C fibre-evoked activity in single neurones of the rat thalamus. Pain. 1990 Apr;41(1):71–80. doi: 10.1016/0304-3959(90)91111-U. [DOI] [PubMed] [Google Scholar]
  13. Lands W. E. The biosynthesis and metabolism of prostaglandins. Annu Rev Physiol. 1979;41:633–652. doi: 10.1146/annurev.ph.41.030179.003221. [DOI] [PubMed] [Google Scholar]
  14. Longhurst J. C., Dittman L. E. Hypoxia, bradykinin, and prostaglandins stimulate ischemically sensitive visceral afferents. Am J Physiol. 1987 Sep;253(3 Pt 2):H556–H567. doi: 10.1152/ajpheart.1987.253.3.H556. [DOI] [PubMed] [Google Scholar]
  15. Lund A., Tjølsen A., Hole K. The apparent antinociceptive effect of desipramine and zimelidine in the tail flick test in rats is mainly caused by changes in tail skin temperature. Pain. 1989 Jul;38(1):65–69. doi: 10.1016/0304-3959(89)90074-2. [DOI] [PubMed] [Google Scholar]
  16. Lynn B. Cutaneous hyperalgesia. Br Med Bull. 1977 May;33(2):103–108. doi: 10.1093/oxfordjournals.bmb.a071408. [DOI] [PubMed] [Google Scholar]
  17. Maier R., Menassé R., Riesterer L., Pericin C., Ruegg M., Ziel R. The pharmacology of diclofenac sodium (Voltarol). Rheumatol Rehabil. 1979;Suppl 2:11–21. [PubMed] [Google Scholar]
  18. Menassé R., Hedwall P. R., Kraetz J., Pericin C., Riesterer L., Sallmann A., Ziel R., Jaques R. Pharmacological properties of diclofenac sodium and its metabolites. Scand J Rheumatol Suppl. 1978;(22):5–16. doi: 10.3109/03009747809097211. [DOI] [PubMed] [Google Scholar]
  19. Milne R. J., Gamble G. D. Habituation to sham testing procedures modifies tail-flick latencies: effects on nociception rather than vasomotor tone. Pain. 1989 Oct;39(1):103–107. doi: 10.1016/0304-3959(89)90180-2. [DOI] [PubMed] [Google Scholar]
  20. Neugebauer V., Schaible H. G., Schmidt R. F. Sensitization of articular afferents to mechanical stimuli by bradykinin. Pflugers Arch. 1989 Dec;415(3):330–335. doi: 10.1007/BF00370884. [DOI] [PubMed] [Google Scholar]
  21. Okuyama S., Aihara H. The mode of action of analgesic drugs in adjuvant arthritic rats as an experimental model of chronic inflammatory pain: possible central analgesic action of acidic nonsteroidal antiinflammatory drugs. Jpn J Pharmacol. 1984 Jun;35(2):95–103. doi: 10.1254/jjp.35.95. [DOI] [PubMed] [Google Scholar]
  22. Pal P., Koley J., Bhattacharyya S., Gupta J. S., Koley B. Cardiac nociceptors and ischemia: role of sympathetic afferents in cat. Jpn J Physiol. 1989;39(1):131–144. doi: 10.2170/jjphysiol.39.131. [DOI] [PubMed] [Google Scholar]
  23. RANDALL L. O., SELITTO J. J. A method for measurement of analgesic activity on inflamed tissue. Arch Int Pharmacodyn Ther. 1957 Sep 1;111(4):409–419. [PubMed] [Google Scholar]
  24. Robinson D. R., McGuire M. B., Bastian D., Kantrowitz F., Levine L. The effects of anti-inflammatory drugs on prostaglandin production by rheumatoid synovial tissue. Prostaglandins Med. 1978 Dec;1(6):461–477. doi: 10.1016/0161-4630(78)90117-9. [DOI] [PubMed] [Google Scholar]
  25. Sacchetti G., Lampugnani R., Battistini C., Mandelli V. Response of pathological ischaemic muscle pain to analgesics. Br J Clin Pharmacol. 1980 Feb;9(2):165–169. doi: 10.1111/j.1365-2125.1980.tb05828.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Shibata M., Ohkubo T., Takahashi H., Inoki R. Modified formalin test: characteristic biphasic pain response. Pain. 1989 Sep;38(3):347–352. doi: 10.1016/0304-3959(89)90222-4. [DOI] [PubMed] [Google Scholar]
  27. Skoutakis V. A., Carter C. A., Mickle T. R., Smith V. H., Arkin C. R., Alissandratos J., Petty D. E. Review of diclofenac and evaluation of its place in therapy as a nonsteroidal antiinflammatory agent. Drug Intell Clin Pharm. 1988 Nov;22(11):850–859. doi: 10.1177/106002808802201102. [DOI] [PubMed] [Google Scholar]
  28. Small R. E. Diclofenac sodium. Clin Pharm. 1989 Aug;8(8):545–558. [PubMed] [Google Scholar]
  29. Staszewka-Barczak J., Ferreira S. H., Vane J. R. An excitatory nociceptive cardiac reflex elicited by bradykinin and potentiated by prostaglandins and myocardial ischaemia. Cardiovasc Res. 1976 May;10(3):314–327. doi: 10.1093/cvr/10.3.314. [DOI] [PubMed] [Google Scholar]
  30. Stebbins C. L., Smith R. C., Longhurst J. C. Effect of prostaglandins on bradykinin-induced visceral-cardiac reflexes. Am J Physiol. 1985 Jul;249(1 Pt 2):H155–H163. doi: 10.1152/ajpheart.1985.249.1.H155. [DOI] [PubMed] [Google Scholar]
  31. Stevens M. K., Yaksh T. L. Time course of release in vivo of PGE2, PGF2 alpha, 6-keto-PGF1 alpha, and TxB2 into the brain extracellular space after 15 min of complete global ischemia in the presence and absence of cyclooxygenase inhibition. J Cereb Blood Flow Metab. 1988 Dec;8(6):790–798. doi: 10.1038/jcbfm.1988.134. [DOI] [PubMed] [Google Scholar]
  32. Terenius L. Biochemical mediators in pain. Triangle. 1981;20(1-2):19–26. [PubMed] [Google Scholar]
  33. Tjølsen A., Berge O. G., Eide P. K., Broch O. J., Hole K. Apparent hyperalgesia after lesions of the descending serotonergic pathways is due to increased tail skin temperature. Pain. 1988 May;33(2):225–231. doi: 10.1016/0304-3959(88)90094-2. [DOI] [PubMed] [Google Scholar]
  34. Tjølsen A., Lund A., Berge O. G., Hole K. An improved method for tail-flick testing with adjustment for tail-skin temperature. J Neurosci Methods. 1989 Jan;26(3):259–265. doi: 10.1016/0165-0270(89)90124-6. [DOI] [PubMed] [Google Scholar]
  35. Tolman E. L., Rosenthale M. E., Capetola R. J., McGuire J. L. Suprofen: the pharmacology and clinical efficacy of a new non-narcotic peripheral analgesic. Clin Rheum Dis. 1984 Aug;10(2):353–368. [PubMed] [Google Scholar]
  36. Vane J., Botting R. Inflammation and the mechanism of action of anti-inflammatory drugs. FASEB J. 1987 Aug;1(2):89–96. [PubMed] [Google Scholar]
  37. Vinegar R., Truax J. F., Selph J. L., Johnston P. R. New analgesic assay utilizing trypsin-induced hyperalgesia in the hind limb of the rat. J Pharmacol Methods. 1990 Mar;23(1):51–61. doi: 10.1016/0160-5402(90)90008-9. [DOI] [PubMed] [Google Scholar]
  38. Vinegar R., Truax J. F., Selph J. L. Quantitative comparison of the analgesic and anti-inflammatory activities of aspirin, phenacetin and acetaminophen in rodents. Eur J Pharmacol. 1976 May;37(1):23–30. doi: 10.1016/0014-2999(76)90004-2. [DOI] [PubMed] [Google Scholar]
  39. Vogt A., Vetterlein F., dal Ri H., Schmidt G. Excitation of afferent fibres in the cardiac sympathetic nerves induced by coronary occlusion and injection of bradykinin. The influence of acetylsalicylic acid and dipyron. Arch Int Pharmacodyn Ther. 1979 May;239(1):86–98. [PubMed] [Google Scholar]
  40. Wall P. D., Woolf C. J. Muscle but not cutaneous C-afferent input produces prolonged increases in the excitability of the flexion reflex in the rat. J Physiol. 1984 Nov;356:443–458. doi: 10.1113/jphysiol.1984.sp015475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Woolf C. J. Evidence for a central component of post-injury pain hypersensitivity. Nature. 1983 Dec 15;306(5944):686–688. doi: 10.1038/306686a0. [DOI] [PubMed] [Google Scholar]
  42. van Kolfschoten A. A., Hagelen F., Hillen F. C., van Noordwijk J. The influence of paracetamol on the anti-inflammatory, the anti-pyretic and the analgesic activity of indomethacin. Arch Int Pharmacodyn Ther. 1983 Sep;265(1):55–60. [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES