title: Sympathetic activation triggers endogenous opioid release and analgesia within peripheral inflamed tissue.
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 alpha(1)-, alpha(2)- and beta(2)-antagonists. alpha(1)-, alpha(2)- and beta(2)-adrenergic receptors were demonstrated on beta-endorphin-containing immune cells and noradrenaline induced adrenergic receptor-specific release of beta-endorphin from immune cell suspensions. This antinociceptive effect of noradrenaline was reversed by micro - and delta-opioid antagonists as well as by anti-beta-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 beta-endorphin, which induces analgesia via activation of peripheral opioid receptors.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Klinikum Benjamin Franklin, Freie Universität, Hindenburgdamm 30, D-12200 Berlin, Germany. W.Binde@unsw.edu.au
authors.forename: Waltraud
authors.initials: W
authors.lastname: Binder
authors.forename: Shaaban A
authors.initials: SA
authors.lastname: Mousa
authors.forename: Nicolle
authors.initials: N
authors.lastname: Sitte
authors.forename: Myriam
authors.initials: M
authors.lastname: Kaiser
authors.forename: Christoph
authors.initials: C
authors.lastname: Stein
authors.forename: Michael
authors.initials: M
authors.lastname: Schäfer
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000698:Analgesia; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005620:Freund's Adjuvant; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D012684:Sensory Thresholds / Q000187:drug effects; D013312:Stress, Physiological / Q000378:metabolism; D013550:Swimming; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism; D013566:Sympathomimetics / Q000494:pharmacology*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D001615:beta-Endorphin / Q000378:metabolism
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D009292:Narcotic Antagonists; D009294:Narcotics; D018340:Receptors, Adrenergic, alpha-1; D018343:Receptors, Adrenergic, beta-2; D013566:Sympathomimetics; D001615:beta-Endorphin; D005620:Freund's Adjuvant; D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine