Acebo Response Mediated Endogenous Opioid Activity On Regulation Of Autonomic Nervous System

The placebo effect is a psychobiological phenomenon that can be attributable to different mechanisms, including expectation of improvement and conditioning. So far, most of the neurobiological mechanisms underlying this complex phenomenon have been studied in the field of pain and analgesia. Substantial evidence implicates the endogenous opioid system in the mediation of placebo effects under conditions of expectation of analgesia. Besides the classie pharmacological approach in which the opioid antagonist naloxone is used, there is now direct evidence that placebos activate the same brain regions which are activated by narcotics, thus indicating that at least some common mechanisms are involved in both placebo and opioid analgesia. The placebo-activated endogenous opioids are also known to act on specific parts of the body as well as on specific systems, such as the respiratory centers. All these findings suggest that the activation of endogenous opioids during placebo analgesia may have an important impact on different body functions. Therefore, we wanted to further investigate whether placebo analgesia affects other systems and apparatuses. For example, the endogenous opioid systems regulate the cardiovascular function in many complex situations, and this regulation occurs through both the sympathetic and parasympathetic nervous system. On the basis of these considerations, we investigated the heart sympathetic and parasympathetic activity during placebo analgesia.The combination of human functional neuroimaging and peripheral nervous activity’s measures can study central-peripheral nervous systems’ interactions in relation to physical health. To test the hypothesis that endogenous opioid modulate the autonomic nervous system, we used positron emission tomography and examined autonomic interaction with endogenous opioid systems on mu-opioid receptors in humans during anticipation of pain and sustained pain with and without placebo administration. Placebo analgesia mediated endogenous opioid activity on the regulation of autonomic nervous activities such as changes in heart rate and skin conductance are found in forebrain including hypothalamus, basal ganglia, nucleus accumbens, amygdala, thalamus, insula and periaqueductal gray matter. The association between endogenous opioid activity in these areas is independent of the association between self-reported pain and endogenous opioid activity. These data demonstrate that endogenous opioid system regulates autonomic control in terms of placebo analgesia response in humans by using the combination of human functional imaging and peripheral autonomic nervous measurements.