title: Opposite effects of the same drug: reversal of topical analgesia by nocebo information.
abstract: 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.
authors.affiliation: Department of Psychology, Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, 9037 Tromsø, Norway.
authors.forename: Per Matti
authors.initials: PM
authors.lastname: Aslaksen
authors.forename: Maria Lorentze
authors.initials: ML
authors.lastname: Zwarg
authors.forename: Hans-Ingvald Hage
authors.initials: HH
authors.lastname: Eilertsen
authors.forename: Marta Maria
authors.initials: MM
authors.lastname: Gorecka
authors.forename: Espen
authors.initials: E
authors.lastname: Bjørkedal
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000698:Analgesia / Q000379:methods* / Q000523:psychology; D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000009:adverse effects; D004644:Emotions; D005260:Female; D006801:Humans; D008012:Lidocaine / Q000008:administration & dosage* / Q000009:adverse effects; D000077442:Lidocaine, Prilocaine Drug Combination; D008297:Male; D064786:Nocebo Effect; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology; D010147:Pain Measurement / Q000187:drug effects* / Q000523:psychology; D011318:Prilocaine / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000779:Anesthetics, Local; D000077442:Lidocaine, Prilocaine Drug Combination; D011318:Prilocaine; D008012:Lidocaine