Pharmaceutisch Weekblad

, Volume 12, Issue 2, pp 41–45 | Cite as

Opioid receptors and pain

  • R. Dirksen
Review Articles


A receptor site is considered to be a transducing factor for effect of the natural ligand. Endorphins and the drugs that mimic their effects (the opiates) are important for analgesia, and consequently the receptor sites involved in actions of opioid drugs are to be considered as relevant to the transmission of pain. The present review describes the distribution of the opioid receptor sites in the central nervous system, and links their presence to pain-specific areas of the central nervous system.


Central nervous system Nociceptors Opioids Pain Receptors 


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  1. 1.
    Pert CB, Snyder SH. Opiate receptors: demonstration in nervous tissue. Science 1973;179:1011–4.PubMedGoogle Scholar
  2. 2.
    Simon EJ, Hiller JM, Edelman I. Stereospecific binding of the potent narcotic analgesic (3H)-etorphine to rat brain homogenate. Proc Natl Acad Sci USA 1973;70:1947–9.PubMedGoogle Scholar
  3. 3.
    Terenius L. Stereospecific interaction between narcotic analgesics and a synaptic plasma membrane fraction of rat cerebral cortex. Acta Pharmacol Toxicol 1973;32:317–20.Google Scholar
  4. 4.
    Hughes J. Isolation of an endogenous compound from the brain with properties similar to morphine. Brain Res 1975;88:295–308.CrossRefPubMedGoogle Scholar
  5. 5.
    Terenius L, Wahlström A. Search for an endogenous ligand for the opiate receptor. Acta Physiol Scand 1975;94:74–81.PubMedGoogle Scholar
  6. 6.
    Dirksen R. The clinical relevance of endorphin receptors. The antinociceptive effectiveness of epidurally or intrathecally injected endorphinomimetics [Dissertation]. Nijmegen: University of Nijmegen, 1983.Google Scholar
  7. 7.
    Goodman RR, Adler BA, Pasternak GW. Regional distribution of opioid receptors. In: Pasternak GW, ed. The opiate receptors. New Jersey: Humana Press, 1988:197–231.Google Scholar
  8. 8.
    Martin WR, Eades CG, Thompson JA, Huppler RE, Gilbert PE. The effects of morphine and nalorphinelike drugs in the non-dependent and morphinedependent chronic spinal dog. J Pharm Exp Ther 1976;231:539–44.Google Scholar
  9. 9.
    Wolozin BL, Pasternak GW. Classification of multiple morphine and enkephalin binding sites in the central nervous system. Proc Natl Acad Sci USA 1981;78:6181–5.PubMedGoogle Scholar
  10. 10.
    Chang K-J, Cuatrecasas P. Multiple opiate receptors: enkephalins and morphine bind to receptors of different specificity. J Biol Chem 1979;26:484–8.Google Scholar
  11. 11.
    Itzhak Y, Hiller JM, Simon EJ. Characterization of specific binding sites for (+)-N-allylnormetazocine in rat membranes. Mol Pharmacol 1985;27:46–52.PubMedGoogle Scholar
  12. 12.
    Kosterlitz HW, Paterson SJ, Robson LE. Characterization of the kappa-subtype of the opiate receptor in the guinea-pig brain. Br J Pharmacol 1981;73:939–49.PubMedGoogle Scholar
  13. 13.
    Schultz R, Faase E, Wuster M, Herz A. Selective receptors forβ-endorphin on the rat vas deferens. Life Sci 1979;24:843–50.CrossRefPubMedGoogle Scholar
  14. 14.
    Contreras PC, DiMaggio DA, O'Donohue TL. An endogenous ligand for the signa opioid binding site. Synapse 1987;1:57–61.CrossRefPubMedGoogle Scholar
  15. 15.
    Dirksen R. Organisatie van het pijnsysteem [Organization of the pain system]. In: Booij LHDJ, Lip H, Rolly G, Van Vijver AED, eds. Nederlands handboek voor de anesthesiologie [Dutch Handbook for anaesthesiology]. Utrecht: Wetenschappelijke Uitgeverij Bunge, 1989:359–72.Google Scholar
  16. 16.
    Traynor JR, Kelly PD, Rance MJ. Multiple opiate binding sites in rat spinal cord. Life Sci 1982;31:1377–80.CrossRefPubMedGoogle Scholar
  17. 17.
    Wood PL, Iyengar S. Central actions of opiates and opioid peptides. In: Pasternak GW, ed. The opiate receptors. New York: Humana Press, 1988:307–57.Google Scholar
  18. 18.
    Schmauss C, Doherty C, Yaksh TL. The analgesic effects of intrathecally administered partial agonist, nalbuphine hydrochloride. Eur J Pharmacol 1983;86:1–7.CrossRefGoogle Scholar
  19. 19.
    Dickenson AH, Sullivan AF, Roques BP. Evidence that endogenous enkephalins and a δ opioid receptor agonist have a common site of action in spinal anti-nociception. Eur J Pharmacol 1989;148:437–9.CrossRefGoogle Scholar
  20. 20.
    Onofrio BM, Yaksh T. Intrathecal delta-receptor ligand produces analgesia in man. Lancet 1983;1:1386–7.CrossRefGoogle Scholar
  21. 21.
    Pinckaers JWM, Nijhuis GMM, Dirksen R. Epidural and spinal nicomorphine: the incidence of side effects. In: Cools AR, Nijhuis GMM, ed. Analgesia by peridural and spinal opiates. Nijmegen: Institute for Anaesthesiology 1980:129–41.Google Scholar
  22. 22.
    Criswell HD. Analgesia and hyperreactivity following morphine microinjection into mouse brain. Pharmacol Biochem Behav 1976;4:23–6.CrossRefPubMedGoogle Scholar
  23. 23.
    Jensen TS, Yaksh TL. Comparison of the antinociceptive action of mu and delta opioid receptor ligands in the periaquaductal gray matter, medial and paramedial ventral medulla in the rat as studied by micro-injection technique. Brain Res 1986;372:301–12.CrossRefPubMedGoogle Scholar
  24. 24.
    Yaksh TL, Al-Rodhan NRF, Jensen TS. Sites of action of opiates in production of analgesia. In: Fields HL, Besson J-M, eds. Progress in brain research; vol. 77. Amsterdam: Elsevier Science Publishers: 1988:371–95.Google Scholar
  25. 25.
    Wood PL, Rackham A, Richard RJ. Spinal analgesia: comparison of the mu agonist morphine and the kappa agonist ethylketazocine. Life Sci 1981;28:2119–25.CrossRefPubMedGoogle Scholar
  26. 26.
    Bodnar RJ, Williams CL, Lee SJ, Pasternak GW. Role ofμ 1-opiate receptors in supraspinal analgesia: a microinjection study. Brain Res 1988;477:25–43.CrossRefGoogle Scholar
  27. 27.
    Smith DJ, Perrotti JM, Crisp T, Cabral MEY, Long JT, Scalzitti JM. Theμ opiate receptor is responsible for descending pain inhibition originating in the periaquaductal gray region of the rat brain. Eur J Pharmacol 1988;156:47–54.CrossRefPubMedGoogle Scholar
  28. 28.
    Tseng L-F, Towell JF, Fujimoto JM. Spinal release of immunoreactive Met-enkephalin by intraventricular beta-endorphin and its analogues in anesthetized rats. J Pharm Exp Ther 1986;237:65–75.Google Scholar
  29. 29.
    Walker GE, Yaksh TL. Studies on the effects of intrathalamically injected DADL and morphine on nociceptive thresholds and electroencephalographic activity: a thalamicδ receptor syndrome. Brain Res 1986;381:1–14.CrossRefPubMedGoogle Scholar
  30. 30.
    Emmers R. Pain: a spike-coded message in the brain. New York: Raven Press, 1981.Google Scholar
  31. 31.
    Jurna I. Dose-dependent inhibition by naloxone of nociceptive activity evoked in the rat thalamus. Pain 1988;35:349–54.CrossRefPubMedGoogle Scholar
  32. 32.
    North RA, Williams JT, Surprenant A, Christie MJ.μ And δ receptors belong to a family of receptors that are coupled to potassium channels. Proc Natl Acad Sci USA 1987;84:5487–91.PubMedGoogle Scholar
  33. 33.
    Shook JE, Kazmierski W, Wire WS, Lemcke PK, Hruby VJ, Burks TF. Opioid receptor selectivity ofβ-endorphinin vitro andin vivo: mu, delta, and epsilon receptors. J Pharm Exp Ther 1988;246:1018–25.Google Scholar
  34. 34.
    Yaksh TL, Rudy TA. Narcotic analgesics. CNS site and mechanism of action as revealed by intracerebral injection techniques. Pain 1978;4:299–359.CrossRefPubMedGoogle Scholar
  35. 35.
    Schmauss C, Yaksh TL.In vivo studies on spinal opiate receptor systems mediating antinociception. II. Pharmacological profiles suggesting a differential association of mu, delta and kappa receptors with visceral and cutaneous thermal stimuli in the rat. J Pharm Exp Ther 1984;228:1–12.Google Scholar
  36. 36.
    Satoh M, Kawaira S, Yamamoto M, Foong F-W, Masuda C. Analgesic action of cyclazocine: blocking nociceptive responses induced by intra-arterial bradykinin injection and tooth pulp stimulation. Arch Int Pharmacol 1979;241:300–6.Google Scholar
  37. 37.
    Inukai T, Takagi H. Site of anti-nociceptive action of a new benzomorphan derivative ID-1229. Arch Int Pharmacodyn Ther 1979;242:262–72.PubMedGoogle Scholar
  38. 38.
    Dehen H, Willer JC, Boureau F, Cambier J. Congenital insensitivity to pain, and endogenous morphinelike sunstances. Lancet 1977;2:293–5.CrossRefPubMedGoogle Scholar
  39. 39.
    Goldfarb J, Hu JW. Enhancement of reflexes by naloxone in spinal cats. Neuropharmacology 1976;15:785–92.CrossRefPubMedGoogle Scholar
  40. 40.
    Levine JD, Gordon NC, Taiwo YD, Coderre TJ. Potentiation of pentazocine analgesia by low-dose naloxone. J Clin Invest 1988;82:1574–7.PubMedGoogle Scholar
  41. 41.
    Vaccarino AL, Tasker RAR, Melzack R. Analgesia produced by normal doses of opioid antagonist alone and in combination with morphine. Pain 1989;36:103–9.CrossRefPubMedGoogle Scholar
  42. 42.
    Taiwo YO, Basbaum AI, Perry F, Levine JD. Paradoxical analgesia produced by low doses of the opiateantagonist naloxone is mediated by interaction at a site with characteristics of the delta opioid receptor. J Pharm Exp Ther 1989;249:97–100.Google Scholar
  43. 43.
    Kraus E, LeBars D. Morphine antagonizes inhibitory controls of nociceptive reactions, triggered by visceral pain in the rat. Brain Res 1986;379:151–6.CrossRefPubMedGoogle Scholar
  44. 44.
    Iadarola MJ, Brady LS, Draisci G, Dubner R. Enhancement of dynorphin gene expression in spinal cord following experimental inflammation: stimulus specificity, behavioural parameters, and opioid receptor binding. Pain 1988;35:313–26.CrossRefPubMedGoogle Scholar
  45. 45.
    Van de Brink FG. Histamine and antihistamines [Dissertation]. Nijmegen: University of Nijmegen, 1969.Google Scholar
  46. 46.
    Dirksen R, Nijhuis GMM. The relevance of cholinergic transmission at the spinal level to opiate effectiveness. Eur J Pharmacol 1983;91:215–21.CrossRefPubMedGoogle Scholar
  47. 47.
    Germany A, Contreras E, Villar M. A comparison of GABAergic influences on the analgesic responses to morphine and pentazocine. Gen Pharmacol 1989;20:157–9.PubMedGoogle Scholar
  48. 48.
    Manner G, Foldes FF, Deery AM, Kuleba M. Acute and chronic effects of morphine on choline acetylase, cholinesterase and acetylcholine in cultured cells of nervous origin. In: Knoll J, Vizi ES, eds. Symposium on analgesics. Budapest: Akademiai Kiadó, 1976:113–9.Google Scholar
  49. 49.
    Seeman P. The membrane actions of anesthetics and tranquilizers. Pharm Rev 1972;24:583–655.PubMedGoogle Scholar
  50. 50.
    Acalovschi I, Ene V, Lörinczi E, Nicolaus F. Saddle block with pethidine for perineal operations. Br J Anaesth 1986;58:1012–6.PubMedGoogle Scholar

Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1990

Authors and Affiliations

  • R. Dirksen
    • 1
  1. 1.Institute for AnaesthesiologyUniversity of NijmegenHB NijmegenThe Netherlands

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