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Effects of Systemic Morphine on Monkeys and Man: Generalized Suppression of Behavior and Preferential Inhibition of Pain Elicited by Unmyelinated Nociceptors

  • Charles J. VierckJr.
  • Brian Y. Cooper
  • Richard H. Cohen
  • David C. Yeomans
  • Ove Franzén
Chapter
Part of the Wenner-Gren Center International Symposium Series book series (EMISS, volume 12)

Abstract

After years of extensive usage, morphine is still regarded as the most powerful pharmacological tool for control of pain. Despite this long record of success in the clinics, it is clear that morphine 1s not am analgesic, in that pain is not obliterated at systemic dosages that leave respiration intact in man (Javert and Hardy, l951). Clinical patients report that pain can be elicited 1n the presence of morphine. Also, the effects of morphine on psychophysical ratings of phas1cally elicited pain are subtle in comparison with subjective estimates of clinical effectiveness (Beecher, 1957). This disparity of clinical and experimental findings has led to a number of hypotheses concerning the primary actions of morphine: (a) Morphine has been claimed to be an anxfolyt1o, and its, action has been likened to the effects of frontal lobotomy, which is said to attenuate the emotional reactions to pain without disturbing the primary sensations of pain (Freeman and Watts, 1948). This explanation suggests that modifications of pain experiences occur by actions of morphine at telenoephal1o sites rather than via the brain stem — spinal cord circuitry that has been emphasized 1n recent attempts to understand central mechanisms of opiate hypalgesfa (Yaksh, 1981). (b) Morphine has been thought to exert preferential effects on chronic pain, as distinct from phasically elicited pain (Beecher° 1957). Clear definitions of the crucial, distinguishing features of chronic pain or of morphine’s effects on pain are not available, but there are a number of possibilities.

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References

  1. Beck, P.W., Handwerker, H.O. (1974). Bradykinin end serotonin effects on various types of cutaneous nerve fibers. Pfluger’s Arch., 347, 209–222CrossRefGoogle Scholar
  2. Beecher, H.K. (1957). The measurement of pain: Prototype for the quantitative study of subjective responses. Pharmacol. Rev., 9, 59–209PubMedGoogle Scholar
  3. Bishop, G.H., Landau, W.M., (1958). Evidence for a double peripheral pathway for pain. Science, 132, 712–713CrossRefGoogle Scholar
  4. Cooper, B.Y., Viercky C.J., Jr., (1980). A comparison of operant and reflexive measures of morphine analgesia. Neuroscience Abstr., 6, 430Google Scholar
  5. D’Amour, F.E., Smith, D. (1941). A method for determining loss of pain sensation. J. Pharmacol. Exp. Ther., 72, 74–79Google Scholar
  6. Douglas, W.W. and Ritchie, J.M. (1962). Mammalian nonmyelinated nerve fibers. Physiol. Rev., 42, 297–334PubMedGoogle Scholar
  7. Fitzgerald, M., Lynn, B. (1977). The sensitization of high threshold mechanoreceptors with myelinated axons by repeated heating. J. Physiol., 365, 549–563Google Scholar
  8. Fjällbrant, N., Iggo, A. (1961). The effect of histamine, 5 hydroxytryptamine and acetylcholine on cutameous afferent fibers. J. physiol., 156, 578–590PubMedCentralPubMedGoogle Scholar
  9. Franz, M., Mense, S. (1975). Muscle receptors with group IV afferent fibers responding to application of bradykinin. Brain Res., 96, 369–383CrossRefGoogle Scholar
  10. Freeman, W., Watts, J.W. (1948). Pain mechanisms and the frontal lobes: a study of pre-frontal lobotomy for intractable pain. Ann. Intern. Med., 28, 747–754PubMedCrossRefGoogle Scholar
  11. Goodman, L.S., Gilman, A. (1975). The Pharmacological Basis of Therapeutics. MacMillan, New YorkGoogle Scholar
  12. Gray, B.G., Dostrovsky, J.O., (1983). Descending inhibitory influences from periaqueductal gray, nucleus raphe magnus, and adjacent reticular formation. I. Effects on lumbar spinal cord nociceptive and nonnociceptive neurons. J. Neurophysiol., 49° 932–947Google Scholar
  13. Haffner, F. (1929). Experimentelle Prufung Schmerzstillender mittel. Deutsch Med. Nschr, 55, 731–733CrossRefGoogle Scholar
  14. Henry, J.L. (1979). Naloxone excites nociceptive units in the lumbar dorsal horn of the spinal cat. Neurnsci., 4, 1485–1491Google Scholar
  15. Jackson, H. (1952). The evaluation of analgesic potency of drugs using thermal stimulation in the rat. Brit. J. Pharmacol., 7, 196–203PubMedCentralPubMedGoogle Scholar
  16. Javert, C.T., Hardy, J.D. (1951). Influence of analgesics on pain intensity during labor (with a note on natural childbirth). Anesthesiol., 12, 189–215CrossRefGoogle Scholar
  17. Jurna, I., Grossman, W., Theres, C. (1973). Inhibition by morphine of repetitive activation of cat spinal motoneurons. Neuropharmacol., 12, 983–993CrossRefGoogle Scholar
  18. Jurna, I., Heinz, G., (1979) Differential effects of morphine and opioid analgesics on A and C fibre-evoked activity in ascending axons of the cat spinal cord. Brain Res., 171, 573–576PubMedCrossRefGoogle Scholar
  19. Kenins, P. (1982). Responses of single nerve fibers to capsaicin applied to the skin. Neuroscience Lett., 29, 83–88CrossRefGoogle Scholar
  20. LaMotte, C., Pert, C.G., Snyder, S.H. (1976). Opiate receptor binding in primate spinal cord: distribution and changes after dorsal root section. Brain Res., 112, 407–412CrossRefGoogle Scholar
  21. LaMotte, R.H., Campbell, J.N. (1978). Comparison of responses of warm and nociceptive C fiber afferents in monkey with human judgements of thermal pain. J. Neurophysiol., 41, 509–528Google Scholar
  22. LeBars, D., Gullbaud, G., Jurna, J., Besson, J.M., (1976). Differential effects of morphine on responses of dorsal horn lamina V type cells elicited by A and C fibre stimulation in the spinal cat. Brain Res., 115, 518–524PubMedCrossRefGoogle Scholar
  23. LeBars, D., Chitour, D., Kraus, E., Clot, A.M., Dickinson, A.H., Besson, J.M. (1981). The effect of systemic morphine upon noxious inhibitory controls (DNIC) in the rat: Evidence for a lifting of certain descending inhibitory controls of dorsal horn convergent neurons. Brain Res., 215, 257–274PubMedCrossRefGoogle Scholar
  24. Perl, E.R., Kumazawa, T., Lynn, B., Kenins, P. (1976). Sensitization of high threshold receptors with unmyelinated (C) afferent fibers. Prog. Brain Res., 43, 263–277PubMedCrossRefGoogle Scholar
  25. Randall, L.O., Selitto, J.J., (1957). A method for measurement of analgesic activity of inflamed tissue. Arch. Int. Pharmacodyn. Ther., 111, 409–419PubMedGoogle Scholar
  26. Siegmund, E.A., Cadmus, R.A. Lu, G., (1957). A method for evaluating non-narcotic and narcotic analgesics. Proc. Soc. Exp. Biol. Med., 95, 729–731PubMedCrossRefGoogle Scholar
  27. Szolcsanyi, J. (1980). Effect of pain-producing chemical agents on the activity of slowly conducting afferent fibres. Acta phys. Acad. Sci. Hung., 56, 86Google Scholar
  28. Torebjörk, H.E., Hallin, R.G. (1973). Perceptual changes accompanying controlled, preferential blocking of A and C fibre responses in intact human skin nerves. Exp. Drain Res., 16, 321–332Google Scholar
  29. Van Hees, J., Gybels, J.M. (1972). Pain related to single afferent C fibers in human shin. Brain Res., 48, 397–400PubMedCrossRefGoogle Scholar
  30. Vierck, C.J., Jr., Cooper, B.Y. (1983). Guidelines for assessing pain reactions and pain modulation in laboratory animal subjects. In Advances in Pain Research andd Therapy, Vol. 6. (Eds. L. Kruger and J. Liebeskind ). Raven Press, New YorkGoogle Scholar
  31. Vierck, C.J. Jr., Cooper, B.Y., Franzen, O., Ritz, L.A., Greenspan, J.D. (1983). Behavioral analysis of CNS pathways and transmitter systems involved in conduction and inhibition of pain sensation and reactions in primates. In Progress in Psychobiology and Physiological Psychology, Vol. 10. (Eds. J. Sprague., A. Epstein). Academic Press, New YorkGoogle Scholar
  32. Woolfe, G., MacDonald, A.D. (1944). The evaluation of the analgesic action of pethidine hydrochloride (Demerol). J. Pharmacol. Exp. Ther., 80, 300–307Google Scholar
  33. Yaksh, T.L. (1978). Analgetic actions of the Intrathecal opiates in cat and primate. Brain Res., 153, 205–210PubMedCrossRefGoogle Scholar
  34. Yaksh, T.L. (1981). Spinal opiate analgesia: Characteristics and principles of action. Pain, 11, 293–346PubMedCrossRefGoogle Scholar
  35. Zotterman, Y. (1939). Touch, pain and tickling: An electrophysiological investigation on cutaneous sensory nerves. J. physiol. 95, 1–28PubMedCentralPubMedGoogle Scholar

Copyright information

© The Wenner-Gren Center 1984

Authors and Affiliations

  • Charles J. VierckJr.
    • 1
  • Brian Y. Cooper
    • 1
  • Richard H. Cohen
    • 1
  • David C. Yeomans
    • 1
  • Ove Franzén
    • 2
  1. 1.Department of Neuroscience and Center for Neurobiological SciencesUniversity of Florida College of MedicineGainesvilleUSA
  2. 2.Department of PsychologyUniversity of UppsalaUppsalaSweden

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