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Erschienen in: Der Schmerz 4/2019

20.06.2019 | Opioide | Übersichten

Schmerzinhibition durch Opioide – neue Konzepte

verfasst von: Prof. Dr. med. C. Stein

Erschienen in: Der Schmerz | Ausgabe 4/2019

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Zusammenfassung

Hintergrund

Opioide sind die ältesten und stärksten Schmerzmedikamente, allerdings sind sie durch gefährliche Nebenwirkungen wie Atemdepression, Suchtpotenzial, Sedierung, Übelkeit und Obstipation limitiert. Die klinische Anwendung ist unbestritten in der Behandlung von akutem (z.B. perioperativem) und tumorassoziiertem Schmerz, jedoch hat die Langzeitanwendung bei chronischem Nichttumorschmerz zunehmend Kritik erfahren und zur aktuellen „Opioidkrise“ beigetragen.

Fragestellung und Ziele

Diese Übersicht behandelt pharmakologische Grundlagen und neue Forschungsstrategien zur Reduktion von Nebenwirkungen. Mechanismen der Schmerzentstehung und -inhibition sowie anderer Opioidwirkungen werden beschrieben. Zur Illustration der klinischen Situation und medizinischer Probleme werden pathophysiologische Veränderungen des Opioidsystems wie Plastizität von Opioidrezeptoren, Signalwegen, endogener Opioide, zentraler und peripherer Wirkorte diskutiert.

Schlussfolgerungen

Der epidemische Fehlgebrauch und Missbrauch von Opioiden hat gezeigt, dass große Wissenslücken in der Behandlung von chronischem Schmerz bestehen, dass Interessenkonflikte und die Validität von Modellen in der Medikamentenentwicklung stärker berücksichtigt werden müssen, und dass dringend neue Schmerzmedikamente ohne Suchtpotenzial gebraucht werden. Aktuell erscheinen die Verstärkung endogener Opioidwirkungen und die selektive Aktivierung peripherer Opioidrezeptoren am vielversprechendsten.
Literatur
1.
Zurück zum Zitat Albert-Vartanian A, Boyd MR, Hall AL et al (2016) Will peripherally restricted kappa-opioid receptor agonists (pKORAs) relieve pain with less opioid adverse effects and abuse potential? J Clin Pharm Ther 41:371–382CrossRefPubMed Albert-Vartanian A, Boyd MR, Hall AL et al (2016) Will peripherally restricted kappa-opioid receptor agonists (pKORAs) relieve pain with less opioid adverse effects and abuse potential? J Clin Pharm Ther 41:371–382CrossRefPubMed
2.
Zurück zum Zitat Altarifi AA, David B, Muchhala KH et al (2017) Effects of acute and repeated treatment with the biased mu opioid receptor agonist TRV130 (oliceridine) on measures of antinociception, gastrointestinal function, and abuse liability in rodents. J Psychopharmacol 31:730–739CrossRefPubMedPubMedCentral Altarifi AA, David B, Muchhala KH et al (2017) Effects of acute and repeated treatment with the biased mu opioid receptor agonist TRV130 (oliceridine) on measures of antinociception, gastrointestinal function, and abuse liability in rodents. J Psychopharmacol 31:730–739CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Baron R, Hans G, Dickenson AH (2013) Peripheral input and its importance for central sensitization. Ann Neurol 74:630–636CrossRefPubMed Baron R, Hans G, Dickenson AH (2013) Peripheral input and its importance for central sensitization. Ann Neurol 74:630–636CrossRefPubMed
5.
Zurück zum Zitat Bassiony MM, Salah El-Deen GM, Yousef U et al (2015) Adolescent tramadol use and abuse in Egypt. Am J Drug Alcohol Abuse 41:206–211CrossRefPubMed Bassiony MM, Salah El-Deen GM, Yousef U et al (2015) Adolescent tramadol use and abuse in Egypt. Am J Drug Alcohol Abuse 41:206–211CrossRefPubMed
6.
Zurück zum Zitat Basso L, Boue J, Auge C et al (2018) Mobilization of CD4+ T lymphocytes in inflamed mucosa reduces pain in colitis mice: toward a vaccinal strategy to alleviate inflammatory visceral pain. Pain 159:331–341CrossRefPubMed Basso L, Boue J, Auge C et al (2018) Mobilization of CD4+ T lymphocytes in inflamed mucosa reduces pain in colitis mice: toward a vaccinal strategy to alleviate inflammatory visceral pain. Pain 159:331–341CrossRefPubMed
7.
Zurück zum Zitat Basso L, Bourreille A, Dietrich G (2015) Intestinal inflammation and pain management. Curr Opin Pharmacol 25:50–55CrossRefPubMed Basso L, Bourreille A, Dietrich G (2015) Intestinal inflammation and pain management. Curr Opin Pharmacol 25:50–55CrossRefPubMed
8.
Zurück zum Zitat Becker WC, Fiellin DA (2017) Abuse-deterrent opioid formulations—putting the potential benefits into perspective. N Engl J Med 376:2103–2105CrossRefPubMed Becker WC, Fiellin DA (2017) Abuse-deterrent opioid formulations—putting the potential benefits into perspective. N Engl J Med 376:2103–2105CrossRefPubMed
10.
Zurück zum Zitat Bhala N, Emberson J, Merhi A et al (2013) Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet 382:769–779CrossRefPubMed Bhala N, Emberson J, Merhi A et al (2013) Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet 382:769–779CrossRefPubMed
11.
Zurück zum Zitat Celik MO, Labuz D, Henning K et al (2016) Leukocyte opioid receptors mediate analgesia via Ca(2+)-regulated release of opioid peptides. Brain Behav Immun 57:227–242CrossRefPubMed Celik MO, Labuz D, Henning K et al (2016) Leukocyte opioid receptors mediate analgesia via Ca(2+)-regulated release of opioid peptides. Brain Behav Immun 57:227–242CrossRefPubMed
12.
Zurück zum Zitat Chou R, Gordon DB, de Leon-Casasola OA et al (2016) Management of postoperative pain: a clinical practice guideline from the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists’ Committee on Regional Anesthesia, executive committee, and administrative council. J Pain 17:131–157CrossRefPubMed Chou R, Gordon DB, de Leon-Casasola OA et al (2016) Management of postoperative pain: a clinical practice guideline from the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists’ Committee on Regional Anesthesia, executive committee, and administrative council. J Pain 17:131–157CrossRefPubMed
13.
Zurück zum Zitat Compton P, Miotto K, Elashoff D (2004) Precipitated opioid withdrawal across acute physical dependence induction methods. Pharmacol Biochem Behav 77:263–268CrossRefPubMed Compton P, Miotto K, Elashoff D (2004) Precipitated opioid withdrawal across acute physical dependence induction methods. Pharmacol Biochem Behav 77:263–268CrossRefPubMed
14.
Zurück zum Zitat Cox BM (2013) Recent developments in the study of opioid receptors. Mol Pharmacol 83:723–728CrossRefPubMed Cox BM (2013) Recent developments in the study of opioid receptors. Mol Pharmacol 83:723–728CrossRefPubMed
15.
Zurück zum Zitat Del Vecchio G, Spahn V, Stein C (2017) Novel opioid analgesics and side effects. Acs Chem Neurosci 8:1638–1640CrossRefPubMed Del Vecchio G, Spahn V, Stein C (2017) Novel opioid analgesics and side effects. Acs Chem Neurosci 8:1638–1640CrossRefPubMed
16.
Zurück zum Zitat Dembla S, Behrendt M, Mohr F et al (2017) Anti-nociceptive action of peripheral mu-opioid receptors by G‑beta-gamma protein-mediated inhibition of TRPM3 channels. Elife 6:e26280CrossRefPubMedPubMedCentral Dembla S, Behrendt M, Mohr F et al (2017) Anti-nociceptive action of peripheral mu-opioid receptors by G‑beta-gamma protein-mediated inhibition of TRPM3 channels. Elife 6:e26280CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Dosen-Micovic L, Ivanovic M, Micovic V (2006) Steric interactions and the activity of fentanyl analogs at the mu-opioid receptor. Bioorg Med Chem 14:2887–2895CrossRefPubMed Dosen-Micovic L, Ivanovic M, Micovic V (2006) Steric interactions and the activity of fentanyl analogs at the mu-opioid receptor. Bioorg Med Chem 14:2887–2895CrossRefPubMed
18.
19.
Zurück zum Zitat Endres-Becker J, Heppenstall PA, Mousa SA et al (2007) Mu-opioid receptor activation modulates transient receptor potential vanilloid 1 (TRPV1) currents in sensory neurons in a model of inflammatory pain. Mol Pharmacol 71:12–18CrossRefPubMed Endres-Becker J, Heppenstall PA, Mousa SA et al (2007) Mu-opioid receptor activation modulates transient receptor potential vanilloid 1 (TRPV1) currents in sensory neurons in a model of inflammatory pain. Mol Pharmacol 71:12–18CrossRefPubMed
20.
Zurück zum Zitat Eriksen J, Sjogren P, Bruera E et al (2006) Critical issues on opioids in chronic non-cancer pain: an epidemiological study. Pain 125:172–179CrossRefPubMed Eriksen J, Sjogren P, Bruera E et al (2006) Critical issues on opioids in chronic non-cancer pain: an epidemiological study. Pain 125:172–179CrossRefPubMed
21.
Zurück zum Zitat Fordyce WE (1992) Opioids, pain and behavioral outcomes. APS J 1:282–284CrossRef Fordyce WE (1992) Opioids, pain and behavioral outcomes. APS J 1:282–284CrossRef
22.
23.
Zurück zum Zitat Graham T, Grocott P, Probst S et al (2013) How are topical opioids used to manage painful cutaneous lesions in palliative care? A critical review. Pain 154:1920–1928CrossRefPubMed Graham T, Grocott P, Probst S et al (2013) How are topical opioids used to manage painful cutaneous lesions in palliative care? A critical review. Pain 154:1920–1928CrossRefPubMed
25.
Zurück zum Zitat Hill R, Disney A, Conibear A et al (2018) The novel mu–opioid receptor agonist PZM21 depresses respiration and induces tolerance to antinociception. Br J Pharmacol 175:2653–2661CrossRefPubMedPubMedCentral Hill R, Disney A, Conibear A et al (2018) The novel mu–opioid receptor agonist PZM21 depresses respiration and induces tolerance to antinociception. Br J Pharmacol 175:2653–2661CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Imam MZ, Kuo A, Ghassabian S et al (2018) Progress in understanding mechanisms of opioid-induced gastrointestinal adverse effects and respiratory depression. Neuropharmacology 131:238–255CrossRefPubMed Imam MZ, Kuo A, Ghassabian S et al (2018) Progress in understanding mechanisms of opioid-induced gastrointestinal adverse effects and respiratory depression. Neuropharmacology 131:238–255CrossRefPubMed
27.
Zurück zum Zitat Jagla CA, Martus P, Stein C (2014) Peripheral opioid receptor blockade increases postoperative morphine demands—a randomized, double-blind, placebo-controlled trial. Pain 155:2056–2062CrossRefPubMed Jagla CA, Martus P, Stein C (2014) Peripheral opioid receptor blockade increases postoperative morphine demands—a randomized, double-blind, placebo-controlled trial. Pain 155:2056–2062CrossRefPubMed
28.
29.
Zurück zum Zitat Lee LA, Caplan RA, Stephens LS et al (2015) Postoperative opioid-induced respiratory depression: a closed claims analysis. Anesthesiology 122:659–665CrossRefPubMed Lee LA, Caplan RA, Stephens LS et al (2015) Postoperative opioid-induced respiratory depression: a closed claims analysis. Anesthesiology 122:659–665CrossRefPubMed
30.
Zurück zum Zitat Leung PTM, Macdonald EM, Stanbrook MB et al (2017) A 1980 letter on the risk of opioid addiction. N Engl J Med 376:2194–2195CrossRefPubMed Leung PTM, Macdonald EM, Stanbrook MB et al (2017) A 1980 letter on the risk of opioid addiction. N Engl J Med 376:2194–2195CrossRefPubMed
31.
Zurück zum Zitat Li JG, Chen C, Yin J et al (1999) ASP147 in the third transmembrane helix of the rat mu opioid receptor forms ion-pairing with morphine and naltrexone. Life Sci 65:175–185CrossRefPubMed Li JG, Chen C, Yin J et al (1999) ASP147 in the third transmembrane helix of the rat mu opioid receptor forms ion-pairing with morphine and naltrexone. Life Sci 65:175–185CrossRefPubMed
32.
Zurück zum Zitat Li Y, van den Pol AN (2008) Mu-opioid receptor-mediated depression of the hypothalamic hypocretin/orexin arousal system. J Neurosci 28:2814–2819CrossRefPubMedPubMedCentral Li Y, van den Pol AN (2008) Mu-opioid receptor-mediated depression of the hypothalamic hypocretin/orexin arousal system. J Neurosci 28:2814–2819CrossRefPubMedPubMedCentral
33.
Zurück zum Zitat Livingston KE, Traynor JR (2018) Allostery at opioid receptors: modulation with small molecule ligands. Br J Pharmacol 175:2846–2856CrossRefPubMed Livingston KE, Traynor JR (2018) Allostery at opioid receptors: modulation with small molecule ligands. Br J Pharmacol 175:2846–2856CrossRefPubMed
34.
Zurück zum Zitat Lüscher C, Slesinger PA (2010) Emerging roles for G protein-gated inwardly rectifying potassium (GIRK) channels in health and disease. Nat Rev Neurosci 11:301–315CrossRefPubMedPubMedCentral Lüscher C, Slesinger PA (2010) Emerging roles for G protein-gated inwardly rectifying potassium (GIRK) channels in health and disease. Nat Rev Neurosci 11:301–315CrossRefPubMedPubMedCentral
35.
Zurück zum Zitat Machelska H (2011) Dual peripheral actions of immune cells in neuropathic pain. Arch Immunol Ther Exp (Warsz) 59:11–24CrossRef Machelska H (2011) Dual peripheral actions of immune cells in neuropathic pain. Arch Immunol Ther Exp (Warsz) 59:11–24CrossRef
36.
Zurück zum Zitat Machelska H, Pflüger M, Weber W et al (1999) Peripheral effects of the kappa-opioid agonist EMD 61753 on pain and inflammation in rats and humans. J Pharmacol Exp Ther 290:354–361PubMed Machelska H, Pflüger M, Weber W et al (1999) Peripheral effects of the kappa-opioid agonist EMD 61753 on pain and inflammation in rats and humans. J Pharmacol Exp Ther 290:354–361PubMed
37.
Zurück zum Zitat Meissner W, Komann M, Erlenwein J et al (2017) The quality of postoperative pain therapy in German hospitals. Dtsch Arztebl Int 114:161–167PubMedPubMedCentral Meissner W, Komann M, Erlenwein J et al (2017) The quality of postoperative pain therapy in German hospitals. Dtsch Arztebl Int 114:161–167PubMedPubMedCentral
38.
Zurück zum Zitat Montandon G, Ren J, Victoria NC et al (2016) G‑protein-gated inwardly rectifying potassium channels modulate respiratory depression by opioids. Anesthesiology 124:641–650CrossRefPubMed Montandon G, Ren J, Victoria NC et al (2016) G‑protein-gated inwardly rectifying potassium channels modulate respiratory depression by opioids. Anesthesiology 124:641–650CrossRefPubMed
39.
Zurück zum Zitat Mousa SA, Straub RH, Schäfer M et al (2007) Beta-endorphin, Met-enkephalin and corresponding opioid receptors within synovium of patients with joint trauma, osteoarthritis and rheumatoid arthritis. Ann Rheum Dis 66:871–879CrossRefPubMedPubMedCentral Mousa SA, Straub RH, Schäfer M et al (2007) Beta-endorphin, Met-enkephalin and corresponding opioid receptors within synovium of patients with joint trauma, osteoarthritis and rheumatoid arthritis. Ann Rheum Dis 66:871–879CrossRefPubMedPubMedCentral
40.
Zurück zum Zitat Nockemann D, Rouault M, Labuz D et al (2013) The K channel GIRK2 is both necessary and sufficient for peripheral opioid-mediated analgesia. EMBO Mol Med 5:1263–1277CrossRefPubMedPubMedCentral Nockemann D, Rouault M, Labuz D et al (2013) The K channel GIRK2 is both necessary and sufficient for peripheral opioid-mediated analgesia. EMBO Mol Med 5:1263–1277CrossRefPubMedPubMedCentral
41.
42.
Zurück zum Zitat Psaty BM, Merrill JO (2017) Addressing the opioid epidemic—opportunities in the postmarketing setting. N Engl J Med 376:1502–1504CrossRefPubMed Psaty BM, Merrill JO (2017) Addressing the opioid epidemic—opportunities in the postmarketing setting. N Engl J Med 376:1502–1504CrossRefPubMed
43.
44.
Zurück zum Zitat Raffa RB, Taylor R Jr., Pergolizzi JV Jr. (2014) Sequestered naltrexone in sustained release morphine or oxycodone—a way to inhibit illicit use? Expert Opin Drug Saf 13:181–190CrossRefPubMed Raffa RB, Taylor R Jr., Pergolizzi JV Jr. (2014) Sequestered naltrexone in sustained release morphine or oxycodone—a way to inhibit illicit use? Expert Opin Drug Saf 13:181–190CrossRefPubMed
45.
Zurück zum Zitat Raja SN (2012) Modulating pain in the periphery: gene-based therapies to enhance peripheral opioid analgesia: bonica lecture, ASRA 2010. Reg Anesth Pain Med 37:210–214CrossRefPubMedPubMedCentral Raja SN (2012) Modulating pain in the periphery: gene-based therapies to enhance peripheral opioid analgesia: bonica lecture, ASRA 2010. Reg Anesth Pain Med 37:210–214CrossRefPubMedPubMedCentral
46.
Zurück zum Zitat Reinecke H, Weber C, Lange K et al (2015) Analgesic efficacy of opioids in chronic pain: recent meta-analyses. Br J Pharmacol 172:324–333CrossRefPubMed Reinecke H, Weber C, Lange K et al (2015) Analgesic efficacy of opioids in chronic pain: recent meta-analyses. Br J Pharmacol 172:324–333CrossRefPubMed
47.
Zurück zum Zitat Richards N, McMahon SB (2013) Targeting novel peripheral mediators for the treatment of chronic pain. Br J Anaesth 111:46–51CrossRefPubMed Richards N, McMahon SB (2013) Targeting novel peripheral mediators for the treatment of chronic pain. Br J Anaesth 111:46–51CrossRefPubMed
48.
50.
Zurück zum Zitat Roques BP, Fournie-Zaluski MC, Wurm M (2012) Inhibiting the breakdown of endogenous opioids and cannabinoids to alleviate pain. Nat Rev Drug Discov 11:292–310CrossRefPubMed Roques BP, Fournie-Zaluski MC, Wurm M (2012) Inhibiting the breakdown of endogenous opioids and cannabinoids to alleviate pain. Nat Rev Drug Discov 11:292–310CrossRefPubMed
51.
Zurück zum Zitat Schmid CL, Kennedy NM, Ross NC et al (2017) Bias factor and therapeutic window correlate to predict safer opioid analgesics. Cell 171:1165–1175.e13CrossRefPubMedPubMedCentral Schmid CL, Kennedy NM, Ross NC et al (2017) Bias factor and therapeutic window correlate to predict safer opioid analgesics. Cell 171:1165–1175.e13CrossRefPubMedPubMedCentral
52.
Zurück zum Zitat Schreiter A, Gore C, Labuz D et al (2012) Pain inhibition by blocking leukocytic and neuronal opioid peptidases in peripheral inflamed tissue. FASEB J 26:5161–5171CrossRefPubMed Schreiter A, Gore C, Labuz D et al (2012) Pain inhibition by blocking leukocytic and neuronal opioid peptidases in peripheral inflamed tissue. FASEB  J 26:5161–5171CrossRefPubMed
53.
Zurück zum Zitat Schubert I, Ihle P, Sabatowski R (2013) Increase in opiate prescription in Germany between 2000 and 2010: a study based on insurance data. Dtsch Arztebl Int 110:45–51PubMedPubMedCentral Schubert I, Ihle P, Sabatowski R (2013) Increase in opiate prescription in Germany between 2000 and 2010: a study based on insurance data. Dtsch Arztebl Int 110:45–51PubMedPubMedCentral
55.
Zurück zum Zitat Schumacher MA, Basbaum AI, Naidu RK (2015) Opioid agonists and antagonists. In: Katzung BG, Trevor AJ (Hrsg) Basic and clinical pharmacology. McGraw-Hill, New York, S 531–551 Schumacher MA, Basbaum AI, Naidu RK (2015) Opioid agonists and antagonists. In: Katzung BG, Trevor AJ (Hrsg) Basic and clinical pharmacology. McGraw-Hill, New York, S 531–551
56.
Zurück zum Zitat Smith SM, Dart RC, Katz NP et al (2013) Classification and definition of misuse, abuse, and related events in clinical trials: ACTTION systematic review and recommendations. Pain 154:2287–2296CrossRefPubMedPubMedCentral Smith SM, Dart RC, Katz NP et al (2013) Classification and definition of misuse, abuse, and related events in clinical trials: ACTTION systematic review and recommendations. Pain 154:2287–2296CrossRefPubMedPubMedCentral
57.
Zurück zum Zitat Soergel DG, Subach RA, Burnham N et al (2014) Biased agonism of the mu-opioid receptor by TRV130 increases analgesia and reduces on-target adverse effects versus morphine: a randomized, double-blind, placebo-controlled, crossover study in healthy volunteers. Pain 155:1829–1835CrossRefPubMed Soergel DG, Subach RA, Burnham N et al (2014) Biased agonism of the mu-opioid receptor by TRV130 increases analgesia and reduces on-target adverse effects versus morphine: a randomized, double-blind, placebo-controlled, crossover study in healthy volunteers. Pain 155:1829–1835CrossRefPubMed
58.
Zurück zum Zitat Spahn V, Del Vecchio G, Labuz D et al (2017) A nontoxic pain killer designed by modeling of pathological receptor conformations. Science 355:966–969CrossRefPubMed Spahn V, Del Vecchio G, Labuz D et al (2017) A nontoxic pain killer designed by modeling of pathological receptor conformations. Science 355:966–969CrossRefPubMed
59.
Zurück zum Zitat Spahn V, Del Vecchio G, Rodriguez-Gaztelumendi A et al (2018) Opioid receptor signaling, analgesic and side effects induced by a computationally designed pH-dependent agonist. Sci Rep 8:8965CrossRefPubMedPubMedCentral Spahn V, Del Vecchio G, Rodriguez-Gaztelumendi A et al (2018) Opioid receptor signaling, analgesic and side effects induced by a computationally designed pH-dependent agonist. Sci Rep 8:8965CrossRefPubMedPubMedCentral
60.
Zurück zum Zitat Spahn V, Stein C (2017) Targeting delta opioid receptors for pain treatment: drugs in phase I and II clinical development. Expert Opin Investig Drugs 26:155–160CrossRefPubMed Spahn V, Stein C (2017) Targeting delta opioid receptors for pain treatment: drugs in phase I and II clinical development. Expert Opin Investig Drugs 26:155–160CrossRefPubMed
61.
64.
Zurück zum Zitat Stein C, Comisel K, Haimerl E et al (1991) Analgesic effect of intraarticular morphine after arthroscopic knee surgery. N Engl J Med 325:1123–1126CrossRefPubMed Stein C, Comisel K, Haimerl E et al (1991) Analgesic effect of intraarticular morphine after arthroscopic knee surgery. N Engl J Med 325:1123–1126CrossRefPubMed
65.
Zurück zum Zitat Stein C, Hassan AH, Przewlocki R et al (1990) Opioids from immunocytes interact with receptors on sensory nerves to inhibit nociception in inflammation. Proc Natl Acad Sci U S A 87:5935–5939CrossRefPubMedPubMedCentral Stein C, Hassan AH, Przewlocki R et al (1990) Opioids from immunocytes interact with receptors on sensory nerves to inhibit nociception in inflammation. Proc Natl Acad Sci U S A 87:5935–5939CrossRefPubMedPubMedCentral
66.
Zurück zum Zitat Stein C, Hassan AHS, Lehrberger K et al (1993) Local analgesic effect of endogenous opioid peptides. Lancet 342:321–324CrossRefPubMed Stein C, Hassan AHS, Lehrberger K et al (1993) Local analgesic effect of endogenous opioid peptides. Lancet 342:321–324CrossRefPubMed
67.
Zurück zum Zitat Stein C, Küchler S (2013) Targeting inflammation and wound healing by opioids. Trends Pharmacol Sci 34:303–312CrossRefPubMed Stein C, Küchler S (2013) Targeting inflammation and wound healing by opioids. Trends Pharmacol Sci 34:303–312CrossRefPubMed
68.
Zurück zum Zitat Stein C, Millan MJ, Shippenberg TS et al (1989) Peripheral opioid receptors mediating antinociception in inflammation. Evidence for involvement of mu, delta and kappa receptors. J Pharmacol Exp Ther 248:1269–1275PubMed Stein C, Millan MJ, Shippenberg TS et al (1989) Peripheral opioid receptors mediating antinociception in inflammation. Evidence for involvement of mu, delta and kappa receptors. J Pharmacol Exp Ther 248:1269–1275PubMed
69.
Zurück zum Zitat Stein C, Pflüger M, Yassouridis A et al (1996) No tolerance to peripheral morphine analgesia in presence of opioid expression in inflamed synovia. J Clin Investig 98:793–799CrossRefPubMedPubMedCentral Stein C, Pflüger M, Yassouridis A et al (1996) No tolerance to peripheral morphine analgesia in presence of opioid expression in inflamed synovia. J Clin Investig 98:793–799CrossRefPubMedPubMedCentral
70.
Zurück zum Zitat Stevens CW (2015) Bioinformatics and evolution of vertebrate nociceptin and opioid receptors. Vitam Horm 97:57–94CrossRefPubMed Stevens CW (2015) Bioinformatics and evolution of vertebrate nociceptin and opioid receptors. Vitam Horm 97:57–94CrossRefPubMed
71.
Zurück zum Zitat Szigethy E, Knisely M, Drossman D (2018) Opioid misuse in gastroenterology and non-opioid management of abdominal pain. Nat Rev Gastroenterol Hepatol 15:168–180CrossRefPubMed Szigethy E, Knisely M, Drossman D (2018) Opioid misuse in gastroenterology and non-opioid management of abdominal pain. Nat Rev Gastroenterol Hepatol 15:168–180CrossRefPubMed
73.
Zurück zum Zitat Vadivelu N, Mitra S, Hines RL (2011) Peripheral opioid receptor agonists for analgesia: a comprehensive review. J Opioid Manag 7:55–68CrossRefPubMed Vadivelu N, Mitra S, Hines RL (2011) Peripheral opioid receptor agonists for analgesia: a comprehensive review. J Opioid Manag 7:55–68CrossRefPubMed
74.
Zurück zum Zitat Valverde A, Gunkel CI (2005) Pain management in horses and farm animals. J Vet Emerg Crit Care 15:295–307CrossRef Valverde A, Gunkel CI (2005) Pain management in horses and farm animals. J Vet Emerg Crit Care 15:295–307CrossRef
75.
Zurück zum Zitat Viscusi ER, Webster L, Kuss M et al (2016) A randomized, phase 2 study investigating TRV130, a biased ligand of the mu-opioid receptor, for the intravenous treatment of acute pain. Pain 157:264–272CrossRefPubMed Viscusi ER, Webster L, Kuss M et al (2016) A randomized, phase 2 study investigating TRV130, a biased ligand of the mu-opioid receptor, for the intravenous treatment of acute pain. Pain 157:264–272CrossRefPubMed
76.
Zurück zum Zitat Vowles KE, McEntee ML, Julnes PS et al (2015) Rates of opioid misuse, abuse, and addiction in chronic pain: a systematic review and data synthesis. Pain 156:569–576CrossRefPubMed Vowles KE, McEntee ML, Julnes PS et al (2015) Rates of opioid misuse, abuse, and addiction in chronic pain: a systematic review and data synthesis. Pain 156:569–576CrossRefPubMed
79.
Zurück zum Zitat Wieschowski S, Chin WWL, Federico C et al (2018) Preclinical efficacy studies in investigator brochures: do they enable risk-benefit assessment? Plos Biol 16:e2004879CrossRefPubMedPubMedCentral Wieschowski S, Chin WWL, Federico C et al (2018) Preclinical efficacy studies in investigator brochures: do they enable risk-benefit assessment? Plos Biol 16:e2004879CrossRefPubMedPubMedCentral
80.
Zurück zum Zitat Williams JT, Ingram SL, Henderson G et al (2013) Regulation of mu-opioid receptors: desensitization, phosphorylation, internalization, and tolerance. Pharmacol Rev 65:223–254CrossRefPubMedPubMedCentral Williams JT, Ingram SL, Henderson G et al (2013) Regulation of mu-opioid receptors: desensitization, phosphorylation, internalization, and tolerance. Pharmacol Rev 65:223–254CrossRefPubMedPubMedCentral
81.
Zurück zum Zitat Wood E (2018) Strategies for reducing opioid-overdose deaths—lessons from Canada. N Engl J Med 378:1565–1567CrossRefPubMed Wood E (2018) Strategies for reducing opioid-overdose deaths—lessons from Canada. N Engl J Med 378:1565–1567CrossRefPubMed
82.
83.
Zurück zum Zitat Zamponi GW, Currie KP (2013) Regulation of Ca(V)2 calcium channels by G protein coupled receptors. Biochim Biophys Acta 1828:1629–1643CrossRefPubMed Zamponi GW, Currie KP (2013) Regulation of Ca(V)2 calcium channels by G protein coupled receptors. Biochim Biophys Acta 1828:1629–1643CrossRefPubMed
84.
Zurück zum Zitat Zeng C, Gao SG, Cheng L et al (2013) Single-dose intra-articular morphine after arthroscopic knee surgery: a meta-analysis of randomized placebo-controlled studies. Arthroscopy 29:1450–1458 e2CrossRefPubMed Zeng C, Gao SG, Cheng L et al (2013) Single-dose intra-articular morphine after arthroscopic knee surgery: a meta-analysis of randomized placebo-controlled studies. Arthroscopy 29:1450–1458 e2CrossRefPubMed
85.
Zurück zum Zitat Zöllner C, Shaqura MA, Bopaiah CP et al (2003) Painful inflammation-induced increase in mu-opioid receptor binding and G‑protein coupling in primary afferent neurons. Mol Pharmacol 64:202–210CrossRefPubMed Zöllner C, Shaqura MA, Bopaiah CP et al (2003) Painful inflammation-induced increase in mu-opioid receptor binding and G‑protein coupling in primary afferent neurons. Mol Pharmacol 64:202–210CrossRefPubMed
86.
Zurück zum Zitat Zöllner C, Stein C (2007) Opioids. In: Stein C (Hrsg) Analgesia. Handbook of Experimental Pharmacology, Bd. 177. Springer, Heidelberg, S 31–63CrossRef Zöllner C, Stein C (2007) Opioids. In: Stein C (Hrsg) Analgesia. Handbook of Experimental Pharmacology, Bd. 177. Springer, Heidelberg, S 31–63CrossRef
Metadaten
Titel
Schmerzinhibition durch Opioide – neue Konzepte
verfasst von
Prof. Dr. med. C. Stein
Publikationsdatum
20.06.2019
Verlag
Springer Medizin
Erschienen in
Der Schmerz / Ausgabe 4/2019
Print ISSN: 0932-433X
Elektronische ISSN: 1432-2129
DOI
https://doi.org/10.1007/s00482-019-0386-y

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