Placeboeffekte bei chronischen Schmerzen: Forschungsstand und klinische Anwendung

Maike Müller; Anne-Kathrin Bräscher

doi:10.1055/s-0043-121683

AINS - Anästhesiologie · Intensivmedizin · Notfallmedizin · Schmerztherapie, Inhaltsverzeichnis

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53(09): 605-617
DOI: 10.1055/s-0043-121683

Topthema

CME-Fortbildung

Georg Thieme Verlag KG Stuttgart · New York

Placeboeffekte bei chronischen Schmerzen: Forschungsstand und klinische Anwendung

Placebo Responses in Chronic Pain: State of Research and Clinical Implications

Maike Müller

,

Anne-Kathrin Bräscher

Abstract

Zusammenfassung

Spielte der Placeboeffekt ehemals vorwiegend eine (eher unliebsame) Rolle bei randomisierten kontrollierten Studien, so treten nun vermehrt die mit dem Placeboeffekt verbundenen Chancen in den Vordergrund. Dieser Beitrag bespricht bisherige Forschungserkenntnisse zum Placeboeffekt bei chronischen Schmerzen und zeigt, wie durch eine gezielte Beeinflussung des therapeutischen Kontexts die Wirksamkeit pharmakologisch aktiver Schmerzmedikamente gesteigert werden kann.

Abstract

Placebo hypoalgesia has been found to play an important role in every health care by modulating patientsʼ responses to pharmacologically active analgesic treatments. It may be seen as reflecting the capacity for endogenous pain modulation. Enhancing the efficacy of analgesic treatments by boosting endogenous pain modulation might be particularly relevant for chronic pain patients. Research into placebo hypoalgesic responses to chronic pain is sparse, however. In healthy subjects, placebo hypoalgesia is induced by expectations of pain relief through verbal information and learning experiences. Here we review the existing evidence on placebo hypoalgesia to chronic pain. To our knowledge, placebo hypoalgesia to chronic pain has been investigated experimentally in chronic back and chronic musculoskeletal pain, neuropathic pain after thoracotomy, and episodic migraine. Results point towards a maintenance of placebo hypoalgesic responses in chronic pain populations, thus highlighting the potential benefit of boosting placebo hypoalgesic responses in the treatment of chronic pain. Strategies on boosting placebo hypoalgesic responses in every day healthcare are presented.

Schlüsselwörter

Placeboeffekt - Placebohypoalgesie - chronischer Schmerz - Erwartung - klassische Konditionierung

Key words

placebo effect - placebo hypoalgesia - chronic pain - expectation - classical conditioning

Volltext

Referenzen

Literatur
1 Colloca L, Lopiano L, Lanotte M. et al. Overt versus covert treatment for pain, anxiety, and Parkinsonʼs disease. Lancet Neurology 2004; 3: 679-684
2 Amanzio M, Pollo A, Maggi G. et al. Response variability to analgesics: a role for non-specific activation of endogenous opioids. Pain 2001; 90: 205-215
3 Bingel U, Wanigasekera V, Wiech K. et al. The effect of treatment expectation on drug efficacy: imaging the analgesic benefit of the opioid remifentanil. Sci Transl Med 2011; 3: 70ra14
4 Benedetti F, Pollo A, Lopiano L. et al. Conscious expectation and unconscious conditioning in analgesic, motor, and hormonal placebo/nocebo responses. J Neurosci 2003; 23: 4315-4323
5 Colloca L, Benedetti F. Nocebo hyperalgesia: how anxiety is turned into pain. Curr Op Anaesthesiol 2007; 20: 435-439 doi:10.1097/ACO.0b013e3282b972fb
6 Colloca L, Miller FG. The nocebo effect and its relevance for clinical practice. Psychosom Med 2011; 73: 598-603 doi:10.1097/PSY.0b013e3182294a50
7 Bräscher AK, Witthöft M, Becker S. The Underestimated Significance of Conditioning in Placebo Hypoalgesia and Nocebo Hyperalgesia. Pain Res Manag 2018; 2018: 6841985 doi:10.1155/2018/6841985
8 Kessner S, Wiech K, Forkmann K. et al. The effect of treatment history on therapeutic outcome: an experimental approach. JAMA Intern Med 2013; 173: 1468-1469 doi:10.1001/jamainternmed.2013.6705
9 Colloca L, Benedetti F. Placebo analgesia induced by social observational learning. Pain 2009; 144: 28-34 doi:10.1016/j.pain.2009.01.033
10 Flaten MA, Aslaksen PM, Lyby PS. et al. The relation of emotions to placebo responses. Philos Trans R Soc Lond B Biol Sci 2011; 366: 1818-1827 doi:10.1098/rstb.2010.0407
11 Geers AL, Wellman JA, Fowler SL. et al. Dispositional optimism predicts placebo analgesia. J Pain 2010; 11: 1165-1171 doi:10.1016/j.jpain.2010.02.014
12 Wager TD, Rilling JK, Smith EE. et al. Placebo-induced changes in FMRI in the anticipation and experience of pain. Science 2004; 303: 1162-1167 doi:10.1126/science.1093065
13 Geuter S, Eippert F, Hindi Attar C. et al. Cortical and subcortical responses to high and low effective placebo treatments. Neuroimage 2013; 67: 227-236 doi:10.1016/j.neuroimage.2012.11.029
14 Eippert F, Finsterbusch J, Bingel U. et al. Direct evidence for spinal cord involvement in placebo analgesia. Science 2009; 326: 404 doi:10.1126/science.1180142
15 Enck P, Bingel U, Schedlowski M. et al. The placebo response in medicine: minimize, maximize or personalize?. Nat Rev Drug Discov 2013; 12: 191-204 doi:10.1038/nrd3923nrd3923
16 Levine JD, Gordon NC, Fields HL. The mechanism of placebo analgesia. Lancet 1978; 2: 654-657
17 Schweinhardt P, Seminowicz DA, Jaeger E. et al. The anatomy of the mesolimbic reward system: a link between personality and the placebo analgesic response. J Neurosci 2009; 29: 4882-4887 doi:10.1523/jneurosci.5634-08.2009
18 Benedetti F, Amanzio M, Rosato R. et al. Nonopioid placebo analgesia is mediated by CB1 cannabinoid receptors. Nat Med 2011; 17: 1228-1230 doi:10.1038/nm.2435
19 Lee HF, Hsieh JC, Lu CL. et al. Enhanced affect/cognition-related brain responses during visceral placebo analgesia in irritable bowel syndrome patients. Pain 2012; 153: 1301-1310 doi:10.1016/j.pain.2012.03.018
20 Schmid J, Langhorst J, Gass F. et al. Placebo analgesia in patients with functional and organic abdominal pain: a fMRI study in IBS, UC and healthy volunteers. Gut 2015; 64: 418-427 doi:10.1136/gutjnl-2013-306648
21 Bushnell MC, Ceko M, Low LA. Cognitive and emotional control of pain and its disruption in chronic pain. Nat Rev Neurosci 2013; 14: 502-511 doi:10.1038/nrn3516
22 Vase L, Robinson ME, Verne GN. et al. The contributions of suggestion, desire, and expectation to placebo effects in irritable bowel syndrome patients. An empirical investigation. Pain 2003; 105: 17-25
23 Vase L, Robinson ME, Verne GN. et al. Increased placebo analgesia over time in irritable bowel syndrome (IBS) patients is associated with desire and expectation but not endogenous opioid mechanisms. Pain 2005; 115: 338-347 doi:10.1016/j.pain.2005.03.014
24 Klinger R, Kothe R, Schmitz J. et al. Placebo effects of a sham opioid solution: a randomized controlled study in patients with chronic low back pain. Pain 2017; 158: 1893-1902 doi:10.1097/j.pain.0000000000000977
25 Charron J, Rainville P, Marchand S. Direct comparison of placebo effects on clinical and experimental pain. Clin J Pain 2006; 22: 204-211 doi:10.1097/01.ajp.0000161526.25374.e5
26 Muller M, Kamping S, Benrath J. et al. Treatment history and placebo responses to experimental and clinical pain in chronic pain patients. Eur J Pain 2016; 20: 1530-1541 doi:10.1002/ejp.877
27 Kam-Hansen S, Jakubowski M, Kelley JM. et al. Altered placebo and drug labeling changes the outcome of episodic migraine attacks. Sci Transl Med 2014; 6: 218ra5 doi:10.1126/scitranslmed.3006175
28 Petersen GL, Finnerup NB, Norskov KN. et al. Placebo manipulations reduce hyperalgesia in neuropathic pain. Pain 2012; 153: 1292-1300 doi:10.1016/j.pain.2012.03.011
29 Petersen GL, Finnerup NB, Grosen K. et al. Expectations and positive emotional feelings accompany reductions in ongoing and evoked neuropathic pain following placebo interventions. Pain 2014; 155: 2687-2698 doi:10.1016/j.pain.2014.09.036
30 de Craen AJ, Lampe-Schoenmaeckers AJ, Kraal JW. et al. Impact of experimentally-induced expectancy on the analgesic efficacy of tramadol in chronic pain patients: a 2 x 2 factorial, randomized, placebo-controlled, double-blind trial. J Pain Symptom Manage 2001; 21: 210-217
31 Peerdeman KJ, van Laarhoven AI, Keij SM. et al. Relieving patientsʼ pain with expectation interventions: a meta-analysis. Pain 2016; 157: 1179-1191 doi:10.1097/j.pain.0000000000000540
32 Colloca L, Benedetti F. How prior experience shapes placebo analgesia. Pain 2006; 124: 126-133 doi:10.1016/j.pain.2006.04.005
33 Deutsche Interdisziplinäre Vereinigung für Schmerztherapie (DIVS). S3-Leitlinie Behandlung akuter perioperativer und posttraumatischer Schmerzen. Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF); 2009. Im Internet: http://www.awmf.org/uploads/tx_szleitlinien/001-025l_S3_Behandlung_akuter_perioperativer_und_posttraumatischer_Schmerzen_abgelaufen.pdf Stand: 06.08.2018
34 Klinger R, Colloca L, Bingel U. et al. Placebo analgesia: clinical applications. Pain 2014; 155: 1055-1058 doi:10.1016/j.pain.2013.12.007
35 Klinger R, Flor H. Clinical and ethical implications of placebo effects: enhancing patientsʼ benefits from pain treatment. Handb Exp Pharmacol 2014; 225: 217-235 doi:10.1007/978-3-662-44519-8_13
36 Doering BK, Rief W. Utilizing placebo mechanisms for dose reduction in pharmacotherapy. Trends Pharmacol Sci 2012; 33: 165-172 doi:10.1016/j.tips.2011.12.001
37 Colloca L, Enck P, DeGrazia D. Relieving pain using dose-extending placebos: a scoping review. Pain 2016; 157: 1590-1598 doi:10.1097/j.pain.0000000000000566
38 Babel P, Bajcar EA, Adamczyk W. et al. Classical conditioning without verbal suggestions elicits placebo analgesia and nocebo hyperalgesia. PLoS One 2017; 12: e0181856 doi:10.1371/journal.pone.0181856
39 Carvalho C, Caetano JM, Cunha L. et al. Open-label placebo treatment in chronic low back pain: a randomized controlled trial. Pain 2016; 157: 2766-2772 doi:10.1097/j.pain.0000000000000700
40 Kaptchuk TJ, Friedlander E, Kelley JM. et al. Placebos without deception: a randomized controlled trial in irritable bowel syndrome. PLoS One 2010; 5: e15591 doi:10.1371/journal.pone.0015591