Ruolo dei fattori neuropsicobiologici nell'analgesia da placebo

ROLE OF NEUROPSYCHOBIOLOGICAL FACTORS IN PLACEBO ANALGESIA. A literature review of articles of the lasts sixty years was performed in the following pages to clarify the knowledge we have today about placebo analgesia, that is one of the most studied placebo effects. Placebo effects are beneficial health outcomes not related to the direct biological effects of an intervention and can be elicited by an agent that is inert. Reductions in pain ratings following the administration of a placebo with expected analgesic properties have been described and this phenomenon is hypothesized to be mediated by the pain-suppressive endogenous opioid system. In fact significant placebo-induced activation of opioid receptor-mediated neurotransmission was observed in both higher-order and subcortical brain regions and recent research in placebo analgesia has demonstrated that several neurotransmitter systems, such as opiate and dopamine, are involved with the placebo effect so that brain nociceptive networks are downregulated in parallel with behavioral analgesia. The activation of endogenous opioid neurotransmission is also associated with reductions in pain report and negative affective state. The pharmacological method confirm this results because naloxone reduce both behavioral and neural placebo effects as well as placebo-induced responses in pain-modulatory cortical structures, pain-modulating areas and the projections to downstream effectors of the descending pain control system. Brain imaging studies published over the last decade, using either positron emission tomography (PET) or functional magnetic resonance imaging (fMRI), suggest that multiple brain regions are involved in this process and the main networks largely overlap those involved in the regulation of emotional processes. The latest scientific evidence has demonstrated that the placebo and the nocebo effects are mediated by psychological mechanisms such as expectation and conditioning. Expectations induced from the surrounding context, positive or negative, and conditioning processes are modulating factors thought to underlie placebo effects: they are balanced in different ways in placebo analgesia and this balance is crucial for the activation of opioid or non-opioid systems. Expectation, trough the reward system, triggers endogenous opioids, whereas conditioning activates specific subsystems. After trying to define correctly the placebo effect and also describing what it is not, we will discuss current cognitive and neurobiological models like expectation-induced activation of the brain reward circuitry, Pavlovian conditioning, and anxiety mechanisms of the nocebo response to understand how complex this phenomenon is, how many factors can influence it and how many clinical implications it could have. Although in most of the cases the placebo response appears to be unpredictable, several factors have been considered in order to explain the placebo analgesic effect: for example, it is widely recognized that placebo analgesia is experience-dependent because it's more likely to occur after a successful analgesic therapy. In modern medicine, the placebo response has often been regarded as a nuisance, but the results of modern research shows that understanding this phenomenon and the way it is generated from the psychosocial context will help to improve clinical trial design and maximize an expectancy effect that is important for clinicians to optimize the health of their patients.