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Blockade of intra-articular adrenergic receptors increases analgesic demands for pain relief after knee surgery

Rheumatology International volume 31, pages 1299–1306 (2011)Cite this article

Abstract

Activation of opioid receptors on peripheral sensory nerve terminals by opioid peptides that are produced and released from immune cells can result in inhibition of inflammatory pain. This study tests the hypothesis that postoperative pain is attenuated endogenously through a local sympathetic neurotransmitter-activated release of opioids in patients undergoing knee surgery. We examined the expression of opioid peptides and adrenergic receptors in cells infiltrating inflamed synovial tissue and we hypothesized that intra-articular (i.a.) administration of the adrenergic receptor antagonist labetalol will increase postoperative analgesic consumption and/or pain intensity in these patients. In a double-blind, randomized manner, 75 patients undergoing therapeutic knee arthroscopy received i.a. placebo (20 ml saline) or labetalol (2.5 or 5 mg in 20 ml saline) at the end of surgery. Postoperative pain intensity was assessed by visual analog and verbal rating scales at rest and on exertion, and by the consumption of morphine via patient-controlled analgesia. Synovial biopsies were taken during the operation for double-immunofluorescence confocal microscopy studies. Alpha1- and beta2-adrenergic receptors were co-expressed in opioid peptide-containing cells. No significant difference was seen in pain scores, but patients receiving 2.5 mg labetalol requested significantly higher amounts of morphine. These findings are consistent with the notion that surgical stress induces sympathetically activated release of endogenous opioids from inflammatory cells and subsequent analgesia via activation of peripheral opioid receptors.

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Acknowledgments

We are grateful to Dr. H. Steinkellner, Department of Traumatology, LKH Klagenfurt and to all our colleagues in the Departments of Anesthesiology and Traumatology, LKH Klagenfurt for invaluable help in patient recruitment. This work was supported by the Deutsche Forschungsgemeinschaft (KFO 100/2).

Conflict of interest statement

The authors state no conflicts of interest.

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Author notes

  1. Shaaban A. Mousa

    Present address: Department of Anesthesiology and Critical Care Medicine, Charité Campus Virchow Klinikum, Berlin, Germany

Affiliations

  1. Department of Anesthesiology, Landeskrankenhaus Klagenfurt, Klagenfurt, Austria

    Ingo Kager, W. Pipam & Rudolf Likar

  2. Department of Anesthesiology and Critical Care Medicine, Freie Universität Berlin, Charité Campus Benjamin Franklin, 12200, Berlin, Germany

    Shaaban A. Mousa & Christoph Stein

  3. Department of Internal Medicine/Rheumatology, Freie Universität Berlin, Charité Campus Benjamin Franklin, 12200, Berlin, Germany

    Joachim Sieper

  4. Department of Anesthesiology and Intensive Medicine, General Hospital Klagenfurt, St. Veiter Strasse 47, 9020, Klagenfurt, Austria

    Rudolf Likar

Authors
  1. Ingo Kager
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  2. Shaaban A. Mousa
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  3. Joachim Sieper
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  4. Christoph Stein
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  5. W. Pipam
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  6. Rudolf Likar
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Correspondence to Rudolf Likar.

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Kager, I., Mousa, S.A., Sieper, J. et al. Blockade of intra-articular adrenergic receptors increases analgesic demands for pain relief after knee surgery. Rheumatol Int 31, 1299–1306 (2011). https://doi.org/10.1007/s00296-010-1489-z

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  • DOI: https://doi.org/10.1007/s00296-010-1489-z

Keywords

  • Inflammation
  • Pain
  • Opioid receptors
  • Peripheral
  • Adrenergic receptors