Pain Response to Open Label Placebo in Induced Acute Pain in Healthy Adult Males,

Tobias Schneider, M.D.; Julian Luethi, M.D.; Eckhard Mauermann, M.D.; Oliver Bandschapp, M.D.; Wilhelm Ruppen, M.D.
 Author Notes
From the Department for Anesthesia, Intensive Care Medicine, Prehospital Emergency Medicine and Pain Therapy, University Hospital of Basel, Basel, Switzerland.
T.S. and J.L. contributed equally to this article.
Submitted for publication December 4, 2018. Accepted for publication October 29, 2019.
Correspondence: Address correspondence to Dr. Schneider: Anesthesiology, Pain Unit, University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerland. tobias.schneider@usb.ch. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Anesthesiology Newly Published on December 2, 2019. doi:https://doi.org/10.1097/ALN.0000000000003076

Abstract
Editor’s Perspective:

What We Already Know about This Topic:

Placebo treatments even if known to the patient to be placebo, so-called “open label placebo,” may be effective in reducing chronic pain

The effects of the extent of placebo education are poorly understood

What This Article Tells Us That Is New:

Using a well-characterized electrical pain sensitization model in human volunteers, the effects of short versus detailed placebo educational protocols were measured

Open label placebo treatment reduced pain sensitization in the volunteers, but the extent of placebo education did not modify these responses

Background: Open label placebos with patient education are effective in reducing chronic pain, and recent studies on their effect on pain have established interest in this field. Nevertheless, data on their effect on acute pain are scarce, and on hyperalgesia and allodynia, absent. This study assessed the effect of open label placebos on acute pain in healthy adult males and the influence of placebo education.

Methods: Thirty-two healthy males were included in this prospective, randomized, assessor-blinded crossover, single-center study assessing pain intensities (via numeric rating scale), area of hyperalgesia (von Frey filament), and allodynia (dry cotton swab) in a pain model utilizing intracutaneous electrical stimulation. The authors compared the effect of intravenous open label placebo on pain compared to no treatment. The authors further examined the effect of placebo on hyperalgesia and allodynia, and the influence of education (short vs. detailed) before placebo application. Saliva cortisol concentrations were also measured.

Results: Pain ratings (median, first to third quartile) were 21% lower during placebo treatment compared to no treatment, 4.0 (3.2 to 4.9) versus 5.1 (4.7 to 5.4), respectively (P = 0.001). The areas of hyperalgesia and allodynia were lower during placebo treatment compared to no treatment (hyperalgesia, 30 cm2 [17 to 47] vs. 55 cm2 [42 to 68], P = 0.003; allodynia, 24 cm2 [11 to 39] vs. 45 cm2 [31 to 62], P = 0.007). This corresponds to reductions of 47%. The extent of placebo education had no effect on pain. Saliva cortisol decreased significantly over time and was under the limit of detectability in the majority of participants in postbaseline measurements in both treatment branches. Baseline cortisol was not associated with the placebo effect or strength applied of current to reach defined pain ratings.

Conclusions: Open label placebos might play a role in multimodal analgesic concepts.