Clinical relevance of contextual factors as triggers of placebo and nocebo effects in musculoskeletal pain

Abstract

Placebo and nocebo effects are embodied psycho-neurobiological responses capable of modulating pain and producing changes at different neurobiological, body at perceptual and cognitive levels. These modifications are triggered by different contextual factors (CFs) presented in the therapeutic encounter between patient and healthcare providers, such as healing rituals and signs. The CFs directly impact on the quality of the therapeutic outcome: a positive context, that is a context characterized by the presence of positive CFs, can reduce pain by producing placebo effects, while a negative context, characterized by the presence of negative CFs, can aggravate pain by creating nocebo effects. Despite the increasing interest about this topic; the detailed study of CFs as triggers of placebo and nocebo effects is still lacked in the management of musculoskeletal pain.Increasing evidence suggest a relevant role of CFs in musculoskeletal pain management. CFs are a complex sets of internal, external or relational elements encompassing: patient's expectation, history, baseline characteristics; clinician's behavior, belief, verbal suggestions and therapeutic touch; positive therapeutic encounter, patient-centered approach and social learning; overt therapy, posology of intervention, modality of treatment administration; marketing features of treatment and health care setting. Different explanatory models such as classical conditioning and expectancy can explain how CFs trigger placebo and nocebo effects. CFs act through specific neural networks and neurotransmitters that were described as mediators of placebo and nocebo effects.Available findings suggest a relevant clinical role and impact of CFs. They should be integrated in the clinical reasoning to increase the number of treatment solutions, boosts their efficacy and improve the quality of the decision-making. From a clinical perspective, the mindful manipulation of CFs represents a useful opportunity to enrich a well-established therapy in therapeutic setting within the ethical border. From a translational perspective, there is a strong need of research studies on CFs close to routine and real-world clinical practice in order to underline the uncertainty of therapy action and help clinicians to implement knowledge in daily practice.

Keywords: Clinical reasoning; Conditioning; Contextual factors; Expectation; Learning; Nocebo; Pain; Placebo; Therapeutic encounter; Therapeutic relationship.

Fig. 1

Psycho-neurobiological mechanism of CFs. The image displays how CFs are capable to influence the brain networks, neurochemistry and therapeutic outcome. The principal neural areas and neurotransmitters involved in placebo and nocebo effects are reported. Abbreviation: rACC = Rostral Anterior Cingulate Cortex; DLPFC = Dorsolateral prefrontal cortex; PAG = Periaqueductal gray

Fig. 2

Influencers of decision-making process. The image presents: a the clinical situation in which meeting patient’s expectation, previous experience and beliefs creates positive therapeutic outcomes; b the clinical situation in which ignoring patient’s expectation, previous experience and beliefs creates negative therapeutic outcomes

Fig. 3

Social interaction and learning. The image displays: a a positive social interaction between patients in waiting room capable to produce positive therapeutic outcome; b a negative social interaction between patients in waiting room capable to produce negative therapeutic outcome

Fig. 4

Therapeutic rituals and overt therapeutic administration. The image displays: a an enrich therapeutic context capable to produce positive therapeutic outcome; b a poor therapeutic context capable to produce negative therapeutic outcome