Interaction between expectancies and drug effects: an experimental investigation of placebo analgesia with caffeine as an active placebo

In a randomised placebo-controlled clinical trial it is assumed that psychosocial effects of the treatment, regression to the mean and spontaneous remission are identical in the drug and placebo group. Consequently, any difference between the groups can be ascribed to the pharmacological effects. Previous studies suggest that side effects of drugs can enhance expectancies of treatment effects in the drug group compared to the placebo group, and thereby increase placebo responses in the drug group compared to the placebo group. The hypothesis that side effects of drugs can enhance expectancies and placebo responses was tested. Painful laser stimuli were delivered to 20 healthy subjects before and after administration of a drink with 0 or 4 mg/kg caffeine. The drink was administered either with information that it contained a painkiller or that it was a placebo. Laser-evoked potentials and reports of pain, expectancy, arousal and stress were measured. Results Four milligrammes per kilogramme of caffeine reduced pain. Information that a painkiller was administered increased the analgesic effect of caffeine compared to caffeine administered with no drug information. This effect was mediated by expectancies. Information and expectancies had no effect on pain intensity when 0 mg/kg was administered. The analgesic effect of caffeine was increased by information that a painkiller was administered. This was due to an interaction of the pharmacological action of the drug and expectancies. Hence, psychosocial effects accompanying a treatment can differ when an active drug is administered compared to a placebo

Reconnaissance report of Kobe Univ. RCUSS geo-hazard team to India

<div><p>Objective</p><p>The perception of pain is susceptible to modulation by psychological and contextual factors. It has been shown that subjects judge noxious stimuli as more painful in a respective suggestive context, which disappears when the modifying context is resolved. However, a context in which subjects judge the painfulness of a nociceptive stimulus in exactly the opposite direction to that of the cues has never been shown so far.</p><p>Methods</p><p>Nociceptive stimuli (300 ms intranasal gaseous CO₂) at the individual pain threshold level were applied after a visual cue announcing the stimulus as either “no pain”, merely a “stimulus”, or “pain”. Among the stimuli at threshold level, other CO₂ stimuli that were clearly below or above pain threshold were randomly interspersed. These were announced beforehand in 12 subjects randomly with correct or incorrect cues, i.e., clearly painful or clearly non-painful stimuli were announced equally often as not painful or painful. By contrast, in a subsequent group of another 12 subjects, the stimuli were always announced correctly with respect to the evoked pain.</p><p>Results</p><p>The random and often incorrect announcement of stimuli clearly below or above pain threshold caused the subjects to rate the stimuli at pain-threshold level in the opposite direction of the cue, i.e., when the stimuli were announced as “pain” significantly more often than as non-painful and vice versa (p < 10^-4). By contrast, in the absence of incongruence between announcement and perception of the far-from-threshold stimuli, stimuli at pain threshold were rated in the cued direction.</p><p>Conclusions</p><p>The present study revealed the induction of associations incongruent with a given message in the perception of pain. We created a context of unreliable cues whereby subjects perceived the stimulus opposite to that suggested by a prior cue, i.e., potentially nociceptive stimuli at pain threshold level that were announced as painful were judged as non-painful and vice versa. These findings are consistent with reported data on the effects of distrust on non-painful cognitive responses.</p></div