Abstract
It is increasingly recognized that the efficacy of medical treatments is determined in critical part by the therapeutic context in which it is delivered. An important characteristic of that context is treatment history. We recently reported first evidence for a carry-over of treatment experience to subsequent treatment response across different treatment approaches. Here we expand on these findings by exploring the psychological and neurobiological underpinnings of the effect of treatment experience on future treatment response in an experimental model of placebo analgesia with a conditioning procedure. In a combined behavioral and neuroimaging study we experimentally induced positive or negative experiences with an analgesic treatment in two groups of healthy human subjects. Subsequently we compared responses to a second, different analgesic treatment between both groups. We found that participants with an experimentally induced negative experience with the first treatment showed a substantially reduced response to a second analgesic treatment. Intriguingly, several psychological trait variables including anxiety, depression and locus of control modulate the susceptibility for the effects of prior treatment experiences on future treatment outcome. These behavioral effects were supported by neuroimaging data which showed significant differences in brain regions encoding pain and analgesia between groups. These differences in activation patterns were present not only during the pain phase, but also already prior to painful stimulation and scaled with the individual treatment response. Our data provide behavioral and neurobiological evidence showing that the influence of treatment history transfers over time and over therapeutic approaches. Our experimental findings emphasize the careful consideration of treatment history and a strictly systematic treatment approach to avoid negative carry-over effects.
Highlights
Experimental and clinical observations suggest that treatment outcome is not solely determined by the genuine characteristics of a treatment, and depends in critical part on the therapeutic context in which it is delivered [1]
We found that the stronger analgesic effect in the positive compared to the negative treatment history group was associated with activity within the striatum and anterior cingulate cortex (ACC) during both pain phases and in the right dorsolateral prefrontal cortex (DLPFC) during the late pain phase [9]
This was studied in an experimental model of analgesia using an analgesic patch as the first treatment and an analgesic ointment treatment as the second analgesic treatment
Summary
Experimental and clinical observations suggest that treatment outcome is not solely determined by the genuine characteristics of a treatment (e.g., pharmacological properties), and depends in critical part on the therapeutic context in which it is delivered [1]. The pivotal role of this factor for the therapeutic outcome is most apparent in experimental placebo analgesia studies involving a conditioning component [4,5,6,7] In these studies the administration of a placebo treatment is combined with a conditioning procedure (e.g., reduction of pain stimulus intensity) in which participants experience analgesia and thereby learn the efficacy of the treatment. Prior experience modulates the efficacy of a subsequently applied active treatment, presumably by inducing treatment-specific expectations, via (pharmacological) conditioning or a combination of both mechanisms; for review see [3]. To date, this influence of prior treatment experience has only been studied within the same treatment approach. Whether the experience with one treatment approach can ‘carry over’ to a subsequent, different treatment, is currently unknown
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