Potentiating placebo-analgesia in clinical practice   January 1st, 2015

Manchikanti and colleagues (2011) make in their paper entitled ‘placebo and nocebo in interventional pain management: a friend or a foe – or simply foes?’ an argument for a revaluation of placebo effects in clinical practice. They make the claim that clinicians should not try to avoid the placebo effect, but should try to potentiate it, as this effect isn’t just unethical and mythical but must seen as a very real phenomenon, which can be understood from a vast body of both psychological and neurophysiological research.

The authors of this ‘focused review’ define placebo effects as inherent parts of the therapeutic response that are not attributable to the properties of active ingredients. They take placebo responses as inexorably tied to the treatment context in which therapist’s attitudes, psychosocial factors affecting the therapeutic relationship, and the patient mind-set are central ingredients. In the paper the authors summarize evidence that shows that therapeutic efficacy is, at least partly, attributable to the correspondence between the proposed treatment and the patient’s own belief system.

To show how placebo-responses are working in clinical practice a general model is proposed. The model consists of three phases (induction, psychophysiological mediators and actualization of effects), which are all individually characterized. Research shows that in the induction phase, wherein it is realized that interventions are always given in a specific form to a specific patient in a specific context, these non-specific treatment aspects can have far-reaching consequences to its ultimate effects. The authors point to the importance of the content of the therapeutic message (expectancy of positive effect, reassurance, empathic), the role of patient’s beliefs and values, their personal history and their innate predispositions and the influence of the therapeutic context (patient-therapeutic relationship, sociocultural factors). All these non-specific factors play a role in the origination of effect.

These effects are mediated by psychophysiological mediators of which the authors name conditioning, cognition, motivation and emotion as psychological factors and the production of endorphins, dopamine and other neurotransmitters/neuromodulators and the activation of central modulatory mechanisms as neurophysiological factors. For clinicians it seems important to realize that conditioning factors as environmental cues that are paired with effective treatment-outcomes, positive expectations of patients regarding finding relief for their burden, motivational as having strong desires for relief and giving hope as a way to dampen strong emotions are all strong predictors for the origination of placebo effects. 

These placebo effects can be categorized as changes in the subjective experience of pain, emotions, quality of life, satisfaction or relative relief, but also in behavioural markers as the amount of analgesic consumed and overt pain behaviour and in changes in physiological markers as nociceptive activity and other objective clinical indicators.

Based on this model of the existence of placebo responses in daily clinical practice, the authors conclude that clinicians shouldn’t strive for initiating false beliefs or exaggerated expectations, but should realize that to exude confidence in the proposed intervention, to build a strong and empathic relationship with their patients and to give reassurance can give strong support to the effect of therapeutic interventions.

Dr. Lennard Voogt 

2015 Pain in Motion


Manchikanti L, Giordano J, Fellows B, Hirsch J. Placebo and nocebo in interventional pain management: a friend or a foe – or simply foes? Pain Physician 2011; 14:E157-E175. Full text available for free!