Skip to main content
Log in

Evidence for analgesia mediated by peripheral opioid receptors in inflamed synovial tissue

  • Originals
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Summary

Intra-articular morphine (5 mg in 25 ml) was administered to patients for post-operative analgesia following arthroscopic knee surgery. At various time intervals, 30 min to 4 h post morphine, venous blood samples were taken in order to determine plasma levels of morphine and its primary metabolites, morphine-3-glucuronide and morphine-6-glucuronide. Measurable amounts of morphine and morphine-3-glucuronide were found in the plasma of 7/10 patients whereas morphine-6-glucuronide was detected in only 2/10 patients. The plasma levels of morphine were lower than that regarded sufficient for post-operative analgesia in all but two patients, indicating a possibility of peripheral analgesia. [p]In addition, synovial biopsy samples were assayed for the presence of opioid binding sites. Tissue samples from 11 different patients were analysed and 6/11 exhibited specific binding of [3H]naloxone, indicating the presence of opioid binding sites/receptors. The receptor type (i. e. μ, δ- or k-) is at present unknown. [p]Taken together, these data provide evidence that locally administered opiates can act on specific opioid receptors in the synovium to mediate analgesia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Appelboom T, DeMaertelaer V, DePrez E, Hauzeur J-P, DeschodtLanckman M (1991) Enkephalinase: a physiologic neuroimmunomodulator detected in the synovial fluid. Arthr Rheum 34: 1048–1051

    Google Scholar 

  • Berkowitz BA, Ngai SH, Yang JC, Hempstead J, Spector S (1975) The disposition of morphine in surgical patients. Clin Pharmacol Ther 17: 629–635

    PubMed  Google Scholar 

  • Dahlstrom B, Bolme P, Feychting H, Noack G, Paalzow L (1979) Morphine kinetics in children. Clin Pharmacol Ther 26: 354–365

    PubMed  Google Scholar 

  • Dahlstrom BE, Tamsen A, Paalzow L (1982) Patient-controlled analgesia therapy; IV Pharmacokinetics and analgesic plasma concentrations of morphine. Clin Pharmacokinet 7: 266–279

    PubMed  Google Scholar 

  • Delay-Goyet P, Kayser V, Zajac JM, Guilbaud G, Besson J-M, Roqwues BP (1989) Lack of significant changes in mu, delta opioid binding sites and neutral endopeptidase EC 3.4.24.11 in the brain and spinal cord of arthritic rats. Neuropbarmacol 28: 1341–1348

    Google Scholar 

  • Gillan MGC, Kosterlitz HW, Paterson S (1980) Comparison of the binding characteristics of tritiated opiates and opioid peptides. Br J Pharmacol 70: 481–490

    PubMed  Google Scholar 

  • Kayser V, Chen YL, Guilbaud G (1991) Behavioural evidence for a peripheral component in the enhanced antinociceptive effect of a low dose of systemic morphine in carrageenin-induced hyperalgesic rats. Brain Res 560: 237–234

    PubMed  Google Scholar 

  • Kayser V, Gobeaux D, Lombard MC, Guilbaud G, Besson J-M (1990) Potent and long lasting antinociceptive effects after injection of low doses of a mu-opioid receptor agonist, fentanyl, into the brachial plexus sheath of the rat. Pain 42: 251–225

    Google Scholar 

  • Kayser V, Guilbaud G (1983) The analgesic effects of morphine, but not those of the enkephalinase inhibitor thiorphan, are enhanced in arthritic rats. Brain Res 267: 131–135

    PubMed  Google Scholar 

  • Matsas R, Kenny AL Turner AJ (1984) The metabolism of neuropeptides: the hydrolysis of peptides, including enkephalins, tachy kinins and their analogues, by endopeptidase 24.11. Biochem J 223: 433–440

    PubMed  Google Scholar 

  • McQuay HJ, Moore RA, Hand CW Sear JW (1987) Potency of oral morphine. Lancet 2: 1458–1459

    Google Scholar 

  • Millan MJ, Czlonkowski A, Pilcher CWT, Almeida OFX, Millan MH, Colpaert FC, Herz A (1987) A model of chronic pain in the rat: functional correlates of alterations in the activity of opioid systems. J Neurosci 7: 77–81

    PubMed  Google Scholar 

  • Nayman J (1979) Measurement and control of postoperative pain. Ann Roy Coll Surg Engl 61: 419–426

    Google Scholar 

  • Osborne R, Joel S, Trew D, Slavin M (1988) Analgesic activity of morphine-6-glucuronide. Lancet 1: 828

    Google Scholar 

  • Sawe J, Kager J, Svensson JO, Rane A (1985) Oral morphine in cancer patients: in vivo kinetics and in vitro hepatic glucuronidation. Br J Clin Pharmacol 19: 495–501

    PubMed  Google Scholar 

  • Sawe J, Svensson JO, Rane A (1983) Morphine metabolism in cancer patients on increasing oral doses - no evidence for autoinduction or dose-dependency. Br J Clin Pharmacol 16: 85–93

    PubMed  Google Scholar 

  • Shimomura K, Kanaat O, Ueki S, Ida S, Oguri K, Yoshimura H, Tsukamoto H (1971) Analgesic effect of morphine glucuronides. Tohaku J Exp Med 105: 45–52

    Google Scholar 

  • Stein C, Comisei K, Haimerl E, Yassouridis A, Lehrberger K, Herz A, Peter K (1991) Analgesic effect of intraarticular morphine after arthroscopic knee surgery. New Engl J Med 325: 1123–1126

    PubMed  Google Scholar 

  • Stein C, Comisel K, Yassouridis A, Herz A, Peter K (1990a) Intraarticular morphine produces analgesia following arthroscopic knee surgery. Anaesthesiol 73: A766

    Google Scholar 

  • Stein C, Gramsch C, Herz A (1990b) Intrinsic mechanisms of antinociception in inflammation: local opioid receptors and betaendorphin. J Neurosci 10: 1292–1298

    PubMed  Google Scholar 

  • Stein C, Millan MJ, Shippenberg TS, Peter K, Herz A (1989) Peripheral opioid receptors mediating antinociceptitivn in inflammation. Evidence for involvement of mu, delta and kappa receptors. J Pharmacol Exp Ther 248: 1269–1275

    PubMed  Google Scholar 

  • Stein C, Millan MJ, Yassouridis A, Herz A (1988) Antinociceptive effects of p- and k-agonists in inflammation are enhanced by a peripheral opioid rQceptor-specific mechanism. Eur J Pharmacol 155: 255–264

    PubMed  Google Scholar 

  • Venn RF, Michalkiewicz A (1990) Fast reliable assay for morphine and its metabolites using high-performance liquid chromatography and native fluorescence detection. J Chromatog 525: 379–388

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lawrence, A.J., Joshi, G.P., Michalkiewiczi, A. et al. Evidence for analgesia mediated by peripheral opioid receptors in inflamed synovial tissue. Eur J Clin Pharmacol 43, 351–355 (1992). https://doi.org/10.1007/BF02220608

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02220608

Key words

Navigation