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Opposite effects of the same drug: reversal of topical analgesia by nocebo information

Aslaksen, Per Matti*; Zwarg, Maria Lorentze; Eilertsen, Hans-Ingvald Hage; Gorecka, Marta Maria; Bjørkedal, Espen

doi: 10.1016/j.pain.0000000000000004
Research Paper
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Several studies have shown that psychological factors such as learning, expectation, and emotions can affect pharmacological treatment and shape both favorable and adverse effects of drugs. This study investigated whether nocebo information provided during administration of an analgesic cream could reverse topical analgesia to hyperalgesia. Furthermore, we tested whether nocebo effects were mediated by negative emotional activation. A total of 142 healthy volunteers (73 women) were randomized into 6 groups. A topical analgesic cream (Emla) was administered together with suggestions of analgesia in 1 group, whereas another group received Emla with suggestions of hyperalgesia. Two other groups received a placebo cream together with the same information as the groups receiving Emla. A fifth group received Emla with no specific information about the effect, and the sixth group received no treatment but the same pain induction as the other groups. Heat pain stimulation (48°C) was administered during a pretest and 2 posttests. Pain was continuously recorded during stimulation, and measures of subjective stress and blood pressure were obtained before the pretest, after the application of cream, and after the posttests. The results revealed that pain was significantly lower in the group receiving Emla with positive information and highest in the groups receiving suggestions of hyperalgesia, regardless of whether Emla or the placebo was administered. Mediation analyses showed that stress and blood pressure mediated hyperalgesia after nocebo suggestions. These results suggest that nocebo information can reverse topical analgesia and that emotional factors can explain a significant proportion of variance in nocebo hyperalgesia.

Suggestions of pain increase are capable of reversing topical analgesia to hyperalgesia. Increased levels of negative emotions mediate the hyperalgesic effect after nocebo suggestions.

Department of Psychology, Faculty of Health Sciences, University of Tromsø—The Arctic University of Norway, 9037 Tromsø, Norway

Corresponding author. Address: Department of Psychology, Faculty of Health Sciences, University of Tromsø—The Arctic University of Norway, 9037 Tromsø, Norway. Tel.: +47 77649234; fax:+47 77 64 52 91. E-mail address: per.aslaksen@uit.no (P. M. Aslaksen).

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

Received July 01, 2014

Received in revised form October 08, 2014

Accepted October 21, 2014

© 2015 International Association for the Study of Pain
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