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Intraventricular morphine produces pain relief, hypothermia, hyperglycaemia and increased prolactin and growth hormone levels in patients with cancer pain

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The effects of analgesic, thermoregulatory and endocrine functions of administering morphine sulphate (0.3mg) into the lateral cerebral ventricle via an Ommaya catheter were assessed in eight patients with cancer pain. Satisfactory control of intractable pain was obtained in these patients, without any change in other sensory modalities. The delay in the onset of pain relief and the duration of analgesia ranged, respectively, from 20 to 40 min and from 12 to 16 h after drug injection. In addition, intraventricular administration of morphine caused a reduction in rectal temperature in these patients at an ambient temperature of 24°C. The hypothermia in response to the injection of morphine was due to cutaneous vasodilation and sweating. There was no change in metabolism or in respiratory evaporative heat loss after morphine injection. Further, 10 to 20 min after intraventricular administration of morphine, the blood levels of prolactin, growth hormone and glucose were elevated in these patients. The changes in temperature and endocrine levels lasted for 1–3 h. In addition to the pain relief, these side-effects of morphine treatment were short-lasting and disappeared as the morphine treatment continued. The results indicate that activation of opiate receptors in the brain produced pain relief, hypothermia (due to cutaneous vasodilation and sweating), and increased blood levels of prolactin, growth hormone and glucose in patients with cancer pain.

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  1. 1.

    Akil H, Liebeskind JC (1975) Monoaminergic mechanisms of stimulation-induced analgesia. Brain Res 94:279–296

  2. 2.

    Baragura S, Ralph T (1973) The analgesic effect of electrical stimulation of the diencephalon and mesencephalon. Brain Res 60:369–379

  3. 3.

    Catlin DH, Poland RE, Gorelick DA, Gerner RH, Hui KK, Rubin RT, Li CH (1980) Intravenous infusion of β-endorphin increases serum prolactin, but not growth hormone or cortisol, in depressed subjects and withdrawing methadone addicts. J Clin Endocrinol Metab 50:1021–1025

  4. 4.

    Chihara K, Arimura A, Coy DH, Schally V (1978) Studies of the interaction of endorphins, substance P and endogenous somatostatin in growth hormone and prolactin release in rats. Endocrinology 102:281–286

  5. 5.

    Collins PI, Wei E, Way EL (1974) Central sites of morphine analgesia. Proc West Pharmacol Soc 17:164–167

  6. 6.

    Dupont A, Cusan L, Garon M, Labrie F, Li CH (1977) β-endorphin: stimulation of growth hormone release in vivo. Proc Natl Acad Sci USA 74:358–362

  7. 7.

    Dupont A, Cusan L, Labrie F, Coy DH, Li CH (1977) Stimulation of prolactin release in the rat by intraventricular injection of β-endorphin and methionine-enkephalin. Biochem Biophys Res Commun 75:76–81

  8. 8.

    Foster LB, Dunn RT (1974) Single-antibody technique of radio-immunoassay of cortisol in unextracted serum or plasma. Clin Chem 20:365–372

  9. 9.

    Harris LS, Dewey WL (1973) Role of cholinergic systems in the central action of narcotic agonists and antagonists. In: Kosterlitz HW, Collier HOJ, Villarreal JE (eds) Agonists and antagonists action of narcotic analgesic drugs. University Park Press, Baltimore, pp 198–206

  10. 10.

    Jacquet YF, Lajtha A (1974) Paradoxical effects after microinjection of morphine in the periaqueductal gray matter in the rat. Science 185:1055–1057

  11. 11.

    Kokka N, Garcia JF, George R, Elliott HW (1972) Growth hormone and ACTH secretion: evidence for an inverse relationship in rats. Endocrinology 90:735–742

  12. 12.

    Leavens ME, Hui CS, Cech DH, Weyland JB, Weston JS (1982) Intrathecal and intraventricular morphine for pain in cancer patients: initial study. J Neurosurg 56:241–245

  13. 13.

    Lees GM, Kosterlitz HW, Waterfield AA (1973) Characteristics of morphine-sensitive release of neurotransmitter substances. In: Kosterlitz HW, Collier HDJ, Villarreal JE (eds) Agonists and antagonists actions of narcotic analgesic durgs. University Park Press, Baltimore, pp 142–152

  14. 14.

    Lenzi A, Galli G, Gandolfini M, Marini G (1985) Intraventricular morphine in paraneoplastic painful syndrome of the cervicofacial region: experience in thirty-eight cases. Neurosurgery 17:6–11

  15. 15.

    Liebeskind JC, Guilbaud G, Besson JM, Oliveras JL (1973) Analgesia from electrical stimulation of the periaqueductal gray matter in the cat: behavioural observations and inhibitory effects on spinal cord interneurons. Brain Res 50:441–446

  16. 16.

    Lin MT, Su CY (1979) Metabolic, respiratory, vasomotor and body temperature responses to β-endorphin and morphine in rabbits. J Physiol (Lond) 295:179–189

  17. 17.

    Lobato RD, Madrid JL, Fatela LV, Rivas JJ, Reig E, Lamas E (1983) Intraventricular morphine for control of pain in terminal cancer patients. J Neurosurg 59:627–633

  18. 18.

    Mayer DJ, Liebeskind JC (1974) Pain reduction by focal electrical stimulation of the brain: an anatomical and behavioral analysis. Brain Res 68:73–93

  19. 19.

    McCann SM, Ojeda SR, Libertun C, Harms PG, Krulich I (1974) Drug-induced alterations in gonadotropin and prolactin release in the rat. In: Zimmermann E, George R (eds) Narcotics and the hypothalamus. Raven Press, New York, pp 121–129

  20. 20.

    Messing RB, Lytle LD (1977) Serotonin-containing neurons: their possible role in pain and analgesia. Pain 4:1–24

  21. 21.

    Meyerson BA (1983) Electrostimulation procedures: effects, presumed rationale, and possible mechanisms. In: Bonica JJ, Lindblom U, Iggo A (eds) Advances in pain research and therapy, vol 5. Raven, New York, pp 495–534

  22. 22.

    Nurchi G (1984) Use of intraventricular and intrathecal morphine in intractable pain associated with cancer. Neurosurgery 15:801–803

  23. 23.

    Odell WD, Rayford DL, Ross GT (1967) Simplified, partially automated method for radioimmunoassay of human thyroid stimulating, growth, luteinizing and follicle stimulating hormone. J Lab Clin Med 70:973–978

  24. 24.

    Oliveras JL, Woda A, Guilbaud G, Besson JM (1974) Inhibition of the jaw opening reflex by electrical stimulation of the periaqueductal gray matter in the awake, unrestrained cat. Brain Res 72:328–331

  25. 25.

    Pert A, Yaksh T (1974) Sites of morphine induced analgesia in the primate brain: relation to pain pathway. Brain Res 80:135–140

  26. 26.

    Rivier C, Vale W, Ling N, Brown M, Guillemin R (1977) Stimulation in vivo of the secretion of prolactin and growth hormone by β-endorphin. Endocrinology 100:238–241

  27. 27.

    Roquefeuil B, Benezech J, Batier C, Frerebeau P, Gros C (1984) Intraventricular administration of morphine in patients with neoplastic intractable pain. Surg Neurol 21:155–158

  28. 28.

    Shaar CJ, Frederickson RCA, Dininger NB, Jackson L (1977) Enkephalin analogue and naloxone modulate the release of growth hormone and prolactin — evidence for regulation by an endogenous opioid peptide in brain. Life Sci 21:853–860

  29. 29.

    Shih CJ, Lin MT (1980) Effects of cholinomimetic drugs on sudomotor, metabolic, respiratory, vasomotor and temperature response in palmar hyperhidrosis. J Neurosurg 53:684–689

  30. 30.

    Sinha YN, Selby FW, Lewis UJ, Vanderlick WP (1973) A homologous radioimmunoassay for human prolactin. J Clin Endocrinol Metab 36:509–514

  31. 31.

    Snyder SH, Childers SR (1979) Opiate receptors and opiate peptides. Rev Neurosci 2:35–64

  32. 32.

    Tolis G, Hickey J, Guyda H (1975) Effects of morphine on serum growth hormone, cortisol, prolactin and thyroid stimulating hormone in man. J Clin Endocrinol Metab 41:797–803

  33. 33.

    Van Vugt DA, Bruni JF, Sylvester PW, Chen HT, Ieiri T, Meites J (1979) Interaction between opiates and hypothalamic dopamine on prolactin release. Life Sci 24:2361–2368

  34. 34.

    Way EL, Shen F (1971) Catecholamines and 5-hydroxytryptamine. In: Clouet DH (ed) Narcotic drugs: biochemical pharmacology. Plenum Press, New York, pp 229–253

  35. 35.

    Yaksh TL (1979) Direct evidence that spinal serotonin and noradrenaline terminals mediate the spinal antinociceptive effects of morphine in the periaqueductal gray. Brain Res 160:180–185

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Correspondence to M. T. Lin.

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Su, C.F., Liu, M.Y. & Lin, M.T. Intraventricular morphine produces pain relief, hypothermia, hyperglycaemia and increased prolactin and growth hormone levels in patients with cancer pain. J Neurol 235, 105–108 (1987). https://doi.org/10.1007/BF00718020

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Key words

  • Pain
  • Morphine
  • Hypothermia
  • Hyperglycemia
  • Prolactin