Context matters: the psychoneurobiological determinants of placebo, nocebo and context-related effects in physiotherapy

Abstract

Background: Placebo and nocebo effects embody psychoneurobiological phenomena where behavioural, neurophysiological, perceptive and cognitive changes occur during the therapeutic encounter in the healthcare context. Placebo effects are produced by a positive healthcare context; while nocebo effects are consequences of negative healthcare context. Historically, placebo, nocebo and context-related effects were considered as confounding elements for clinicians and researchers. In the last two decades this attitude started to change, and the understanding of the value of these effects has increased. Despite the growing interest, the knowledge and the awareness of using the healthcare context to trigger placebo and nocebo effects is currently limited and heterogeneous among physiotherapists, reducing their translational value in the physiotherapy field.

Objectives: To introduce the placebo, nocebo and context-related effects by: (1) presenting their psychological models; (2) describing their neurophysiological mechanisms; (3) underlining their impact for the physiotherapy profession; and (4) tracing lines for future researches.

Conclusion: Several psychological mechanisms are involved in placebo, nocebo and context-related effects; including expectation, learning processes (classical conditioning and observational learning), reinforced expectations, mindset and personality traits. The neurophysiological mechanisms mainly include the endogenous opioid, the endocannabinoid and the dopaminergic systems. Neuroimaging studies have identified different brain regions involved such as the dorsolateral prefrontal cortex, the rostral anterior cingulate cortex, the periaqueductal gray and the dorsal horn of spine. From a clinical perspective, the manipulation of the healthcare context with the best evidence-based therapy represents an opportunity to trigger placebo effects and to avoid nocebo effects respecting the ethical code of conduct. From a managerial perspective, stakeholders, organizations and governments should encourage the assessment of the healthcare context aimed to improve the quality of physiotherapy services. From an educational perspective, placebo and nocebo effects are professional topics that should be integrated in the university program of health and medical professions. From a research perspective, the control of placebo, nocebo and context-related effects offers to the scientific community the chance to better measure the impact of physiotherapy on different outcomes and in different conditions through primary studies.

Keywords: Conditioning; Contextual factors; Expectation; Learning; Nocebo effect; Pain; Physical therapy modalities; Placebo effect; Rehabilitation; Therapeutic outcome.

Fig. 1

Contextual factors in clinical practice. The following contextual factors were accepted as effective modifiers of physiotherapy outcomes. For a review of this topic see reviews [16, 17, 19]. a Physiotherapist’s features: professionalism (expertise, qualification, reputation, education, trining); mindset (behaviour, beliefs, expectation, previous experience); appearance (attire, uniform, white coat, trustworthiness). b Patient’s features: mindset (expectation, previous experience, history of treatment, preference, desire, and emotion); baseline (level of symptoms, comorbidity, health condition, gender, age). c Patient-physiotherapist relationship: verbal communication (positive message, tone of voice, active listening, suggestions of support and encouragement, language reciprocity, warmth, attention, care, empathetic interaction); non-verbal communication (eye contact, facial caring expression, smiling, posture, gestures, head nodding, forward leaning, open body orientation). d Treatment features: therapeutic touch (emotional, empathetic, affective); modality (level of invasiveness, open/overt application, observational/social learning); posology (personalized treatment, treatment delivered by the same physiotherapist, cleanliness, adequate length of the consultation, punctuality, flexibility with patient’s appointments, timely and efficient treatment, adequate frequency, duration and follow-up of therapy); marketing (brand, prize, novelty, rituality). e Healthcare setting features: positive distractors (natural lighting, low noise levels, relaxing and soft music, pleasing aromas, adequate temperature); supportive indications (highly visible and easy to read signs, parking information, accessible entrances, clear and consistent verbal or written directions, information desks and accessible electronic information); comfort element (windows and skylights, private therapeutic settings, good access to services, convenient clinic hours, location, parking, and available and approachable support staff); decorations and ornaments (nature artworks, green vegetation, flowers, water, plants, garden, colour)

Fig. 2

Psychobiological determinants of placebo, nocebo and context-related effects. Principal psychobiological determinants of placebo, nocebo and context related effects

Fig. 3

Neurophysiological mechanisms of placebo, nocebo and context-related effects. Principal neurobiological mechanisms of placebo, nocebo and context related effects. a Pharmacological studies. The opioid and cannabinoid systems are involved in placebo and nocebo effects. In some circumstances, placebo analgesia occurs through the activation of the opioid system and can be reversed by naloxone. In other circumstances, placebo analgesia occurs through the activation of the cannabinoid system and can be reversed by rimonabant. Anticipatory anxiety can activate the pro-nociceptive cholecystokinin (CCK) system, leading to nocebo hyperalgesia. The pro-nociceptive CCK effect can be reversed by proglumide and agonized by pentagastrin. b Neuroimaging studies. The activation and deactivation of different brain regions during placebo analgesia and nocebo hyperalgesia have been described trough different brain imaging studies. c Electrophysiological studies. Electroencephalographic (EEG) studies showed the dynamical studies showed the dynamical and temporal changes that occur in the brain before and after the administration of inert treatments