Can drug-related information reverse the effects of a local anesthetic cream? An investigation into the nocebo hyperalgesic response

Abstract

Objective: Verbal information accompanying administration of a drug has been shown to modulate treatment outcome, in both positive and negative directions. If drug effects alter as a function of verbal suggestions, negative information may potentially abolish or even reverse treatment effects. To test whether nocebo information can reverse the effect of a drug, we investigated how such information modified the effect of a local anesthetic cream (Emla) on heat pain. Based on previous research, we further hypothesized that there would be an increase in negative emotions in the form of elevated levels of sympathetic arousal and stress in the groups receiving nocebo information. Method: Onehundredandfifty healthy volunteers (76 females) participated in a Six-Condition X Six-Trial between-subjects design, whereby heat pain was induced to the right volar forearm. Pain intensity was rated on a 10-mm visual analogue scale (COVAS), and negative emotional activation was assessed by skin conductance level (SCL), subjective stress ratings and systolic blood pressure measurements. Results: Nocebo information about the effect of Emla reversed its analgesic properties into hyperalgesia. The nocebo hyperalgesic response was accompanied by increased SCL and subjective stress, which indicates that the negative information about the effect of the cream led to increased psychological and sympathetic arousal. Conclusions: Negative information produced the opposite response of the intended effect of an anesthetic cream. The notion that mental processes overrode the biological effects of a pharmacologically based analgesic treatment may have important implications for clinical practice.