Sympathetic activation triggers endogenous opioid release and analgesia within peripheral inflamed tissue

Authors

  • Waltraud Binder,

    1. Department of Anesthesiology and Critical Care Medicine, Klinikum Benjamin Franklin, Freie Universität, Hindenburgdamm 30, D-12200 Berlin, Germany
    Search for more papers by this author
  • Shaaban A. Mousa,

    1. Department of Anesthesiology and Critical Care Medicine, Klinikum Benjamin Franklin, Freie Universität, Hindenburgdamm 30, D-12200 Berlin, Germany
    Search for more papers by this author
  • Nicolle Sitte,

    1. Department of Anesthesiology and Critical Care Medicine, Klinikum Benjamin Franklin, Freie Universität, Hindenburgdamm 30, D-12200 Berlin, Germany
    Search for more papers by this author
  • Myriam Kaiser,

    1. Department of Anesthesiology and Critical Care Medicine, Klinikum Benjamin Franklin, Freie Universität, Hindenburgdamm 30, D-12200 Berlin, Germany
    Search for more papers by this author
  • Christoph Stein,

    1. Department of Anesthesiology and Critical Care Medicine, Klinikum Benjamin Franklin, Freie Universität, Hindenburgdamm 30, D-12200 Berlin, Germany
    Search for more papers by this author
  • Michael Schäfer

    1. Department of Anesthesiology and Critical Care Medicine, Klinikum Benjamin Franklin, Freie Universität, Hindenburgdamm 30, D-12200 Berlin, Germany
    Search for more papers by this author

  • *

    Present address: Department of Physiology & Pharmacology, School of Medical Sciences, University of New South Wales, Sydney 2052, Australia.

Dr W. Binder, *present address below.
E-mail: W.Binder@unsw.edu.au

Abstract

Stress induces analgesia by mechanisms within and outside the brain. Here we show that the sympathetic nervous system is an essential trigger of intrinsic opioid analgesia within peripheral injured tissue. Noradrenaline, injected directly into inflamed hind paws of male Wistar rats, produced dose-dependent antinociception, reversible by α1-, α2- and β2-antagonists. α1-, α2- and β2-adrenergic receptors were demonstrated on β-endorphin-containing immune cells and noradrenaline induced adrenergic receptor-specific release of β-endorphin from immune cell suspensions. This antinociceptive effect of noradrenaline was reversed by µ- and δ-opioid antagonists as well as by anti-β-endorphin. Stress-induced peripheral analgesia was abolished by chemical sympathectomy and by adrenergic antagonists. These findings indicate that sympathetic neuron-derived noradrenaline stimulates adrenergic receptors on inflammatory cells to release β-endorphin, which induces analgesia via activation of peripheral opioid receptors.

Ancillary