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. 1978 Sep;64(1):91–98. doi: 10.1111/j.1476-5381.1978.tb08645.x

Enhancement of a nociceptive reaction by opioid antagonists in mice.

J J Jacob, K Ramabadran
PMCID: PMC1668273  PMID: 698486

Abstract

1. The opioid antagonists, naloxone, GPA 2163, levallorphan and Mr-2266 reduced the latency of the jumping reaction of mice in the hot plate test. The (+)-isomers of levallorphan and Mr-2266 which are devoid of antagonistic activity did not increase this latency. 2. In the same nociceptive reaction test, the enhancing effect of naloxone progressed in a dose-range similar to that required for the antagonism by naloxone of the depressive action of morphine. 3. The facilitatory effect of naloxone was not blocked by the previous administration of morphine or etorphine but it was prevented by pretreatment with a high dose of buprenorphine. 4. The antagonism by naloxone of morphine and of buprenorphine did not follow the same pattern. 5. The factors which are or may be involved in the efficacy of naloxone in enhancing nociceptive reactions are discussed. 6. The enhancing effect of naloxone may be due to an antagonism of endogenous ligands for the opiate receptor. If so, these ligands would be involved in reaction to but not in perception of nociceptive stimuli which need not be harmful ones.

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Selected References

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  1. Akil H., Mayer D. J., Liebeskind J. C. Antagonism of stimulation-produced analgesia by naloxone, a narcotic antagonist. Science. 1976 Mar 5;191(4230):961–962. doi: 10.1126/science.1251210. [DOI] [PubMed] [Google Scholar]
  2. Audigier Y., Malfroy-Camine B., Schwartz J. C. Binding of 3H-Leu-enkephalin in rat striatum: partial inhibition by morphine or naloxone. Eur J Pharmacol. 1977 Jan 21;41(2):247–248. doi: 10.1016/0014-2999(77)90220-5. [DOI] [PubMed] [Google Scholar]
  3. BEECHER H. K. The measurement of pain; prototype for the quantitative study of subjective responses. Pharmacol Rev. 1957 Mar;9(1):59–209. [PubMed] [Google Scholar]
  4. Bell J. A., Martin W. R. The effect of the narcotic antagonists naloxone, naltrexone and nalorphine on spinal cord C-fiber reflexes evoked by electrical stimulation or radiant heat. Eur J Pharmacol. 1977 Mar 21;42(2):147–154. doi: 10.1016/0014-2999(77)90354-5. [DOI] [PubMed] [Google Scholar]
  5. Berkowitz B. A. The relationship of pharmacokinetics to pharmacological activity: morphine, methadone and naloxone. Clin Pharmacokinet. 1976;1(3):219–230. doi: 10.2165/00003088-197601030-00004. [DOI] [PubMed] [Google Scholar]
  6. Berntson G. G., Walker J. M. Effect of opiate receptor blockade on pain sensitivity in the rat. Brain Res Bull. 1977 Mar-Apr;2(2):157–159. doi: 10.1016/0361-9230(77)90014-4. [DOI] [PubMed] [Google Scholar]
  7. Birdsall N. J., Hulme E. C. C fragment of lipotropin has a high affinity for brain opiate receptors. Nature. 1976 Apr 29;260(5554):793–795. doi: 10.1038/260793a0. [DOI] [PubMed] [Google Scholar]
  8. Clarke F. H., Hill R. T., Saelens J. K., Yokoyama N. Antagonists in the 5-phenyl-benzomorphan series. Adv Biochem Psychopharmacol. 1973;8(0):81–89. [PubMed] [Google Scholar]
  9. Cowan A., Lewis J. W., Macfarlane I. R. Agonist and antagonist properties of buprenorphine, a new antinociceptive agent. Br J Pharmacol. 1977 Aug;60(4):537–545. doi: 10.1111/j.1476-5381.1977.tb07532.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cox B. M., Opheim K. E., Teschemacher H., Goldstein A. A peptide-like substance from pituitary that acts like morphine. 2. Purification and properties. Life Sci. 1975 Jun 15;16(12):1777–1782. doi: 10.1016/0024-3205(75)90272-6. [DOI] [PubMed] [Google Scholar]
  11. El-Sobky A., Dostrovsky J. O., Wall P. D. Lack of effect of naloxone on pain perception in humans. Nature. 1976 Oct 28;263(5580):783–784. doi: 10.1038/263783a0. [DOI] [PubMed] [Google Scholar]
  12. Elliott H. W., Spiehler V., Navarro G. Effect of naloxone on antinociceptive activity of phenoxybenzamine. Life Sci. 1976 Dec 1;19(11):1637–1643. doi: 10.1016/0024-3205(76)90068-0. [DOI] [PubMed] [Google Scholar]
  13. Goldfarb J., Hu J. W. Enhancement of reflexes by naloxone in spinal cats. Neuropharmacology. 1976 Dec;15(12):785–792. doi: 10.1016/0028-3908(76)90009-5. [DOI] [PubMed] [Google Scholar]
  14. Goldstein A., Hilgard E. R. Failure of the opiate antagonist naloxone to modify hypnotic analgesia. Proc Natl Acad Sci U S A. 1975 Jun;72(6):2041–2043. doi: 10.1073/pnas.72.6.2041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Goldstein A., Pryor G. T., Otis L. S., Larsen F. On the role of endogenous opioid peptides: failure of naloxone to influence shock escape threshold in the rat. Life Sci. 1976 Mar 15;18(6):599–604. doi: 10.1016/0024-3205(76)90339-8. [DOI] [PubMed] [Google Scholar]
  16. Grevert P., Goldstein A. Effects of naloxone on experimentally induced ischemic pain and on mood in human subjects. Proc Natl Acad Sci U S A. 1977 Mar;74(3):1291–1294. doi: 10.1073/pnas.74.3.1291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Grevert P., Goldstein A. Some effects of naloxone on behavior in the mouse. Psychopharmacology (Berl) 1977 Jul 18;53(2):111–113. doi: 10.1007/BF00426478. [DOI] [PubMed] [Google Scholar]
  18. Gráf L., Rónai A., Bajusz S., Csheh G., Székely J. I. Opioid agonist activity of beta-lipotropin fragments: a possible biological source of morphine-like substances in the pituitary. FEBS Lett. 1976 Apr 15;64(1):181–184. doi: 10.1016/0014-5793(76)80278-5. [DOI] [PubMed] [Google Scholar]
  19. Guillemin R., Ling N., Burgus R. Endorphines, peptides, d'origine hypothalamique et neurohypophysaire à activité morphinomimétique. Isolement et structure moléculaire de l'alpha-endorphine. C R Acad Sci Hebd Seances Acad Sci D. 1976 Feb 23;282(8):783–785. [PubMed] [Google Scholar]
  20. HALEY T. J., MCCORMICK W. G. Pharmacological effects produced by intracerebral injection of drugs in the conscious mouse. Br J Pharmacol Chemother. 1957 Mar;12(1):12–15. doi: 10.1111/j.1476-5381.1957.tb01354.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hardy J. D., Wolff H. G., Goodell H. STUDIES ON PAIN. A NEW METHOD FOR MEASURING PAIN THRESHOLD: OBSERVATIONS ON SPATIAL SUMMATION OF PAIN. J Clin Invest. 1940 Jul;19(4):649–657. doi: 10.1172/JCI101168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hughes J. Isolation of an endogenous compound from the brain with pharmacological properties similar to morphine. Brain Res. 1975 May 2;88(2):295–308. doi: 10.1016/0006-8993(75)90391-1. [DOI] [PubMed] [Google Scholar]
  23. Hughes J., Smith T. W., Kosterlitz H. W., Fothergill L. A., Morgan B. A., Morris H. R. Identification of two related pentapeptides from the brain with potent opiate agonist activity. Nature. 1975 Dec 18;258(5536):577–580. doi: 10.1038/258577a0. [DOI] [PubMed] [Google Scholar]
  24. JACOB J., BLOZOVSKI M. [Action of some analgesics on the behavior of mice exposed to a thermoanalgesic stimulus. II. Immediate nociceptive response. Differential actions of analgesic and psychoactive substances on the leeching and jumping reactions]. Arch Int Pharmacodyn Ther. 1961 Oct 1;133:296–309. [PubMed] [Google Scholar]
  25. Jacob J. J., Michaud G. M. Production par la Naloxone d'Effets Inverses de Ceux de la Morphine chez le Chien Eveillé. Arch Int Pharmacodyn Ther. 1976 Aug;222(2):322–340. [PubMed] [Google Scholar]
  26. Jacob J. J., Tremblay E. C., Colombel M. C. Facilitation de réactions nociceptives par la naloxone chez la souris et chez le rat. Psychopharmacologia. 1974 Jul 11;37(3):217–223. doi: 10.1007/BF00421535. [DOI] [PubMed] [Google Scholar]
  27. Leimgruber W., Mohacsi E., Baruth H., Randall L. O. Levallorphan and related compounds. Adv Biochem Psychopharmacol. 1973;8(0):45–50. [PubMed] [Google Scholar]
  28. Li C. H., Chung D. Primary structure of human beta-lipotropin. Nature. 1976 Apr 15;260(5552):622–624. doi: 10.1038/260622a0. [DOI] [PubMed] [Google Scholar]
  29. Lord J. A., Waterfield A. A., Hughes J., Kosterlitz H. W. Endogenous opioid peptides: multiple agonists and receptors. Nature. 1977 Jun 9;267(5611):495–499. doi: 10.1038/267495a0. [DOI] [PubMed] [Google Scholar]
  30. Madden J., 4th, Akil H., Patrick R. L., Barchas J. D. Stress-induced parallel changes in central opioid levels and pain responsiveness in the rat. Nature. 1977 Jan 27;265(5592):358–360. doi: 10.1038/265358a0. [DOI] [PubMed] [Google Scholar]
  31. Mayer D. J., Price D. D., Rafii A. Antagonism of acupuncture analgesia in man by the narcotic antagonist naloxone. Brain Res. 1977 Feb;121(2):368–372. doi: 10.1016/0006-8993(77)90161-5. [DOI] [PubMed] [Google Scholar]
  32. Merz H., Langbein A., Stockhaus K., Walther G., Wick H. Structure-activity relationships in narcotic antagonists with N-furylmethyl substituents. Adv Biochem Psychopharmacol. 1973;8(0):91–107. [PubMed] [Google Scholar]
  33. Oliveras J. L., Hosobuchi Y., Redjemi F., Guilbaud G., Besson J. M. Opiate antagonist, naloxone, strongly reduces analgesia induced by stimulation of a raphe nucleus (centralis inferior). Brain Res. 1977 Jan 21;120(2):221–229. doi: 10.1016/0006-8993(77)90902-7. [DOI] [PubMed] [Google Scholar]
  34. Pasternak G. W., Goodman R., Snyder S. H. An endogenous morphine-like factor in mammalian brain. Life Sci. 1975 Jun 15;16(12):1765–1769. doi: 10.1016/0024-3205(75)90270-2. [DOI] [PubMed] [Google Scholar]
  35. Pert A., Walter M. Comparison between naloxone reversal of morphine and electrical stimulation induced analgesia in the rat mesencephalon. Life Sci. 1976 Oct 1;19(7):1023–1032. doi: 10.1016/0024-3205(76)90294-0. [DOI] [PubMed] [Google Scholar]
  36. Pomeranz B., Cheng R., Law P. Acupuncture reduces electrophysiological and behavioral responses to noxious stimuli: pituitary is implicated. Exp Neurol. 1977 Jan;54(1):172–178. doi: 10.1016/0014-4886(77)90243-6. [DOI] [PubMed] [Google Scholar]
  37. Pomeranz B., Chiu D. Naloxone blockade of acupuncture analgesia: endorphin implicated. Life Sci. 1976 Dec 1;19(11):1757–1762. doi: 10.1016/0024-3205(76)90084-9. [DOI] [PubMed] [Google Scholar]
  38. Terenius L. Opioid peptides and opiates differ in receptor selectivity. Psychoneuroendocrinology. 1977;2(1):53–58. doi: 10.1016/0306-4530(77)90031-2. [DOI] [PubMed] [Google Scholar]
  39. Tremblay E., Colombel M. C., Jacob J. Précipitation et prévention de l'abstinence chez le rat et la souris en état de dépendance aiguë. Comparison de la naloxone, de la naltrexone et de la diprenorphine. Psychopharmacology (Berl) 1976 Aug 26;49(1):41–48. [PubMed] [Google Scholar]
  40. Tulunay F. C., Sparber S. B., Takemori A. E. The effect of dopaminergic stimulation and blockade on the nociceptive and antinociceptive responses of mice. Eur J Pharmacol. 1975 Aug;33(1):65–70. doi: 10.1016/0014-2999(75)90139-9. [DOI] [PubMed] [Google Scholar]
  41. Woolf C. J., Barrett G. D., Mitchell D., Myers R. A. Naloxone-reversible peripheral electroanalgesia in intact and spinal rats. Eur J Pharmacol. 1977 Oct 1;45(3):311–314. doi: 10.1016/0014-2999(77)90016-4. [DOI] [PubMed] [Google Scholar]
  42. Yaksh T. L., Yeung J. C., Rudy T. A. An inability to antagonize with naloxone the elevated nociceptive thresholds resulting from electrical stimulation of the mesencephalic central gray. Life Sci. 1976 Jun 1;18(11):1193–1198. doi: 10.1016/0024-3205(76)90192-2. [DOI] [PubMed] [Google Scholar]

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