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Spinal Opioid Analgesia

A Critical Update

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Summary

Small spinal (intrathecal or extrathecal) doses of opioids induce a long-lasting and regional analgesic effect in various experimental animal models. Nowadays extrathecal morphine administration is considered an established method of controlling postoperative and cancer-induced pain conditions.

The potency of morphine applied by the spinal route is higher than when the drug is applied by the intravenous (IV) route. Opioids which are more lipophilic than morphine will provide a marginally better analgesic effect when administered by the spinal route as compared with the IV route.

Several controlled clinical trials in postoperative patients have demonstrated that a single dose of morphine administered by the spinal route gives a more long-lasting action than a similar IV dose. It is not known whether frequent patient-controlled administration of morphine may provide equally good analgesia without additional side effects. The use of spinal morphine in the treatment of cancer-related pain is based on clinical experience only.

There are risks in replacing opioid administration by the oral or IV route with spinal opioids. Morphine should only be used in selected cases until the advantage of spinal opioid analgesia to control postoperative and cancer pain has been clearly defined in well-designed clinical studies. Spinal morphine dosages must be individualised according to the intensity of the nociceptive stimuli and should take into account intra-individual variability in drug responses due to pharmacokinetic and pharmacodynamic factors

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References

  • Arnér S, Arnér B. Differential effects of epidural morphine in the treatment of cancer-related pain. Acta Anaesthesiologica Scandinavica 29: 32–36, 1985

    Article  PubMed  Google Scholar 

  • Banning AM, Schmidt JF, Chraemmer-Jørgensen B, Risbo A. Comparison of oral controlled-release morphine and epidural morphine in the management of postoperative pain. Anesthesia and Analgesia 65: 385–388, 1986

    Article  PubMed  CAS  Google Scholar 

  • Bengtsson M, Löfström B, Merits H. Postoperative pain relief with intrathecal morphine after major hip surgery. Regional Anaesthesie 8: 139–143, 1983

    Google Scholar 

  • Bromage PR, Camporesi EM, Durant PAC, Nielsen CH. Non-respiratory side effects of epidural morphine. Anesthesia and Analgesia 61: 490–495, 1982

    PubMed  CAS  Google Scholar 

  • Bryant RM, Olley JE, Tyers MB. Antinociceptive actions of morphine and buprenorphine given intrathecally in the conscious rat. British Journal of Pharmacology 78: 659–663, 1983

    Article  PubMed  CAS  Google Scholar 

  • Carl P, Crawford ME, Raulo O, Bach V. Long term treatment with epidural opioids. Anaesthesia 41: 32–38, 1986

    Article  PubMed  CAS  Google Scholar 

  • Colpaert FC, Leysen JE, Michiels M, van den Hoogen RHWM. Epidural and intravenous sufentanil in the rat: analgesia, opiate receptor binding, and drug concentrations in plasma and brain. Anesthesiology 65: 41–49, 1986

    Article  PubMed  CAS  Google Scholar 

  • Copper BY, Vierck Jr CJ, Yoemans DC. Selective reduction of second pain sensations by systemic morphine in man. Pain 24: 93–116, 1986

    Article  Google Scholar 

  • Cousins MJ, Mather LE. Intrathecal and epidural administration of opioids. Anesthesiology 61: 276–310, 1984

    Article  PubMed  CAS  Google Scholar 

  • Durant PAC, Yaksh TL. Epidural injections of bupivacaine, morphine, fentanyl, lofentanil and DADL in chronically implanted rats: a pharmacologic and pathologic study. Anesthesiology 64: 43–53, 1986

    Article  PubMed  CAS  Google Scholar 

  • Gustafsson LL. Spinal opiate analgesia: clinical and experimental aspects. Thesis, Karolinska Institute, Stockholm, 1985

    Google Scholar 

  • Gustafsson LL, Post C. The degree of analgesia correlates to spinal morphine concentrations after intrathecal administration in rats. Acta Pharmacologica et Toxicologica 58: 243–248, 1986

    Article  PubMed  CAS  Google Scholar 

  • Gustafsson LL, Post C, Edvardsen B, Ramsay CH. Distribution of morphine and meperidine after intrathecal administration in rat and mouse. Anesthesiology 63: 483–489, 1985

    Article  PubMed  CAS  Google Scholar 

  • Gustafsson LL, Schildt B, Jacobsen K. Adverse effects of extra-dural and intrathecal opiates: report of a nationwide survey in Sweden. British Journal of Anaesthesia 54: 479–986, 1982

    Article  PubMed  CAS  Google Scholar 

  • Herz A, Teschemachen HS. Activities and sites of antinociceptive action of morphine-like analgesics and kinetics of distribution following intravenous, intracerebral and intraventricular application. Advances in Drug Research 6: 79–119, 1971

    CAS  Google Scholar 

  • Lanz E, Theiss D, Riess W, Sommer E. Epidural morphine for postoperative analgesia: a double-blind study. Anesthesia and Analgesia 61: 236–240, 1982

    Article  PubMed  CAS  Google Scholar 

  • Le Bars D, Guilbaud G, Jurna I, Besson JM. Differential effects of morphine on responses of dorsal horn lamina V-type cells elicited by A and C fiber stimulation in the spinal cat. Brain Research 115: 518–524, 1976

    Article  PubMed  Google Scholar 

  • Malone BT, Beye R, Walker J. Management of pain in the terminally ill by administration of epidural narcotics. Cancer 55: 438–440, 1985

    Article  PubMed  CAS  Google Scholar 

  • Millan MJ. Multiple opioid systems and pain. Pain 27: 303–347, 1986

    Article  PubMed  CAS  Google Scholar 

  • Nordberg G. Epidural versusintrathecal route of opioid administration. International Anesthesiology Clinics 24: 93–111, 1986

    Article  PubMed  CAS  Google Scholar 

  • Nordberg G, Hedner T, Mellstrand T, Dahlström B. Pharmacokinetic aspects of epidural morphine analgesia. Anesthesiology 58: 545–551, 1983

    Article  PubMed  CAS  Google Scholar 

  • Nordberg G, Hedner T, Mellstrand T, Dahlström B. Pharmacokinetic aspects of intrathecal morphine analgesia. Anesthesiology 60: 448–454, 1984

    Article  PubMed  CAS  Google Scholar 

  • Przewlocki R, Stala L, Greczek M, Shearman GT, Przewlocka B, et al. Analgesic effects of mu-, delta- and kappa-opiate agonists and, in particular, dynorphin at the spinal level. Life Sciences 33 (Suppl. 1): 649–652, 1983

    Article  PubMed  CAS  Google Scholar 

  • Rawal N, Arnér S, Gustafsson LL, Allvin R. Present state of extradural and intradural opioid analgesia in Sweden: a nationwide follow-up survey. British Journal of Anaesthesia 59: 791–799, 1987

    Article  PubMed  CAS  Google Scholar 

  • Rawal N, Möllefors K, Axelsson K, Lindgårdh G, Widman B. An experimental study of urodynamic effects of epidural morphine and of nalaxone reversal. Anesthesia and Analgesia 62: 641–647, 1983

    Article  PubMed  CAS  Google Scholar 

  • Rawal N, Sjöstrand UH, Dahlström B, Nydahl PA, Östelius J. Epidural morphine for postoperative pain relief: a comparative study with intramuscular narcotic and intercostal nerve block. Anesthesia and Analgesia 61: 93–98, 1982

    Article  PubMed  CAS  Google Scholar 

  • Rawal N, Wattwil M. Respiratory depression after epidural morphine — an experimental and clinical study. Anesthesia and Analgesia 63: 8–14, 1984

    PubMed  CAS  Google Scholar 

  • Säwe J. Oral morphine and methadone in the treatment of cancer pain: clinical pharmacokinetic studies. Thesis, Karolinska Institute, Stockholm, 1984

    Google Scholar 

  • Schmauss C, Yaksh TL. In vivostudies on spinal opiate receptor systems mediating antinociception. II. Pharmacological profiles suggesting a differential association of mu, delta and kappa receptors with visceral chemical and cutaneous thermal stimuli in the rat. Journal of Pharmacology and Experimental Therapuetics 228: 1–12, 1984

    CAS  Google Scholar 

  • Sjöström S, Hartvig P, Tamsen A. Patient-controlled analgesia with epidural morphine and pethidine. British Journal of Anaesthesia 60: 358–366, 1988

    Article  PubMed  Google Scholar 

  • Stenseth R, Sellevold O, Breivik H. Epidural morphine for postoperative pain: experience with 1085patients. Acta Anaesthe-siologica Scandinavica 29: 148–156, 1985

    Article  CAS  Google Scholar 

  • Tamsen A, Gordh T. Epidural clonidine produces analgesia. Lancet II: 231–232, 1985

    Google Scholar 

  • Terenius L. Families of opioid peptides and classes of opioid receptors. In Fields et al. (Eds). Advances in pain research and therapy 9, pp. 461–477, Raven Press, New York, 1985

    Google Scholar 

  • Yaksh TL. Spinal opiate analgesia characteristics and principles of action. Pain 11: 293–346, 1981

    Article  PubMed  CAS  Google Scholar 

  • Yaksh TL, Harty GS, Onofrio BM. High doses of spinal morphine produce a nonopiate receptor-mediated hyperesthesia: clinical and theoretic implications. Anesthesiology 64: 590–597, 1986

    Article  PubMed  CAS  Google Scholar 

  • Yaksh TL, Noueihed R, Durant PAC. Studies of the pharmacology and pathology of intrathecally administered 4-anilinopiperidine analogues and morphine in the rat and cat. Anesthesiology 64: 54–66, 1986

    Article  PubMed  CAS  Google Scholar 

  • Yaksh TL, Reddy SVR. Studies in the primate on the analgesic effects associated with intrathecal opiates, alfa-adrenergic agonists and baclofen. Anesthesiology 54: 451–467, 1981

    Article  PubMed  CAS  Google Scholar 

  • Yaksh TL, Rudy TA. Analgesia mediated by a direct spinal action of narcotics. Science 192: 1357–1358, 1976

    Article  PubMed  CAS  Google Scholar 

  • Yaksh TL, Rudy TA. Studies on the direct spinal action of narcotics in the production of analgesia in the rat. Journal of Pharmacology and Experimental Therapuetics 202: 411–428, 1977

    CAS  Google Scholar 

  • Yeung JC, Rudy TA. Multiplicative interactions between narcotic agonisms expressed at spinal and supraspinal sites of antinociceptive action as revealed by concurrent intrathecal and intracerebroventricular injections of morphine. Journal of Pharmacology and Experimental Therapeutics 215: 633–642, 1980

    PubMed  CAS  Google Scholar 

  • Weddel SJ, Ritter RR. Serum levels following epidural administration of morphine and correlation with relief of postsurgical pain. Anesthesiology 54: 210–214, 1981

    Article  PubMed  CAS  Google Scholar 

Download references

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Authors and Affiliations

  1. Departments of Clinical Pharmacology and Neurophysiology, Karolinska Institute, Huddinge University Hospital, S-141 86, Huddinge, Sweden

    Lars L. Gustafsson & Zsuzsanna Wiesenfeld-Hallin

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  1. Lars L. Gustafsson
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  2. Zsuzsanna Wiesenfeld-Hallin
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Gustafsson, L.L., Wiesenfeld-Hallin, Z. Spinal Opioid Analgesia. Drugs 35, 597–603 (1988). https://doi.org/10.2165/00003495-198835060-00001

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  • DOI: https://doi.org/10.2165/00003495-198835060-00001

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