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Placebo effects of a sham opioid solution: a randomized controlled study in patients with chronic low back pain

Klinger, Reginea,*; Kothe, Ralphb,c; Schmitz, Juliaa; Kamping, Sandraa; Flor, Hertad,e

doi: 10.1097/j.pain.0000000000000977
Research Paper
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This study tested the experimental placebo effect in a group of chronic pain patients. Forty-eight patients having chronic back pain participated in a randomized clinical trial that tested the efficacy of a sham opioid solution (NaCl) compared with an alleged neutral, completely inactive solution (NaCl). We shaped the placebo effect by 2 interventions: verbal instruction and conditioning. The patients were either told that the “solution reduces pain and improves physical capacity” or the “solution is neutral, a placebo.” Half of each group was additionally conditioned (coupling solution with reduced experimental pain), yielding 4 subgroups with 12 participants each. Outcome measures were as follows: the patients' clinical back pain ratings and acute pain ratings (both examined by numerical rating scale 0-10) and self-rated functional capacity (0%-100%; time required for the exercise). Expected pain relief before and after solution intake was also assessed. The inactive solution (NaCl), when presented as an effective treatment (sham “opioid” solution), induced placebo analgesia as evident in lower ratings of the patients' clinical back pain (F(3.12,144.21) = 25.05, P < 0.001), acute pain ratings (F(1.99,87.40) = 18.12, P < 0.01), and time needed to complete a series of daily activities exercises (F(1,44) = 8.51, P < 0.01) as well as increased functional capacity (F(1,44.00) = 19.42, P < 0.001). The 2 manipulations (instruction and conditioning) changed pain expectations, and they were maintained in both sham opioid groups. The results suggest that it may be clinically useful to explicitly integrate placebo analgesia responses into pain management.

Supplemental Digital Content is Available in the Text.Placebos associated with the instruction “highly effective opioid” and additional conditioning reduce experimental and clinical pain and improve physical capacity of chronic back pain patients.

aDepartment of Anesthesiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

bDepartment of Spinal Surgery, Schön Klink Hamburg Eilbek, Hamburg, Germany

cDepartment of Orthopedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

dDepartment of Clinical and Cognitive Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany

eDepartment of Psychology, University of Mannheim, Mannheim, Germany

Corresponding author. Address: Department of Anesthesiology, Pain Therapy and Pain Psychology, Center for Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg-Eppendorf (UKE), Martinistraße 52, 20246 Hamburg, Germany. E-mail address: Tel.: +49 40 7410 52837; fax: +49 40 7410 44963 (R. Klinger).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

Received December 23, 2016

Received in revised form May 24, 2017

Accepted May 30, 2017

© 2017 International Association for the Study of Pain
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