Nocebo and pain: an overview of the psychoneurobiological mechanisms

Introduction: Nocebo effects are defined as adverse events related to negative expectations and learning processes that are involved in the modulation of the descending pain pathways. Research over the last couple of decades has illustrated that behavioral, psychoneurobiological, and functional changes occur during nocebo-induced pain processing. Objectives: We aimed to review published human and nonhuman research on algesia and hyperalgesia resulting from negative expectations and nocebo effects. Methods: Herein, we searched and comprehensively reviewed scientific literature providing informative knowledge about the psychoneurobiological bases of the nocebo effect in the field of pain with an emphasis on how pain processes are shaped by both cognitive and noncognitive factors. Results: Negative expectations are formed through verbal suggestions of heightened pain, prior nociceptive and painful experiences, and observation of pain in others. Susceptibility to the nocebo effect can be also influenced by genetic variants, conscious and nonconscious learning processes, personality traits, and psychological factors. Moreover, providers' behaviors, environmental cues and the appearance of medical devices can induce negative expectations that dramatically influence pain perception and processing in a variety of pain modalities and patient populations. Conclusion: Importantly, we concluded that nocebo studies outline how individual expectations may lead to physiological changes underpinning the central integration and processing of magnified pain signaling. Further research is needed to develop strategies that can identify patients with nocebo-vulnerable pain to optimize the psychosocial and therapeutic context in which the clinical encounter occurs, with the ultimate purpose of improving clinical outcomes.