Placebo effects on human μ-opioid activity during pain

Abstract

Placebo-induced expectancies have been shown to decrease pain in a manner reversible by opioid antagonists, but little is known about the central brain mechanisms of opioid release during placebo treatment. This study examined placebo effects in pain by using positron-emission tomography with [ 11 C]carfentanil, which measures regional -opioid receptor availability in vivo. Noxious thermal stimulation was applied at the same temperature for placebo and control conditions. Placebo treatment affected endogenous opioid activity in a number of predicted -opioid receptorrich regions that play central roles in pain and affect, including periaqueductal gray and nearby dorsal raphe and nucleus cuneiformis, amygdala, orbitofrontal cortex, insula, rostral anterior cingulate, and lateral prefrontal cortex. These regions appeared to be subdivided into two sets, one showing placebo-induced opioid activation specific to noxious heat and the other showing placeboinduced opioid reduction during warm stimulation in anticipation of pain. These findings suggest that a mechanism of placebo analgesia is the potentiation of endogenous opioid responses to noxious stimuli. Opioid activity in many of these regions was correlated with placebo effects in reported pain. Connectivity analyses on individual differences in endogenous opioid system activity revealed that placebo treatment increased functional connectivity between the periaqueductal gray and rostral anterior cingulate, as hypothesized a priori, and also increased connectivity among a number of limbic and prefrontal regions, suggesting increased functional integration of opioid responses. Overall, the results suggest that endogenous opioid release in core affective brain regions is an integral part of the mechanism whereby expectancies regulate affective and nociceptive circuits.neuroimaging ͉ periaqueductal gray ͉ expectancy ͉ affective neuroscience

Personality Trait Predictors of Placebo Analgesia and Neurobiological Correlates

“…Additional regions where endogenous opioid responses to placebo administration were predicted by these personality traits largely overlap with those identified in previous reports as responsive to placebo administration and involved in the regulation of the pain experience Wager et al, 2007;Zubieta et al, 2005): subgenual ACC, dorsal ACC, OFC, anterior and posterior insula, amygdala and, at lower thresholds, PAG, thalamus and dorsolateral prefrontal cortex. As previously observed, activation of m-opioid receptor mediated neurotransmission in some of these regions were associated with reductions in individual pain report.…”

Nociception and autonomic nervous system

“…In contrast, the ventrolateral column receives convergent input from both the superficial and deep dorsal horn relaying nociceptive afferent information from visceral, muscle, and C-fiber skin nociceptors as well as visceral inputs from the nucleus of the NTS and sacral spinal cord. Functional neuroimaging studies in humans indicate that PAG activation by nociceptive inputs is modulated by attention, emotion, expectation of pain and expectation-related placebo analgesia [54][55][56][57][58][59][60][61]. Experimental studies using chemical microstimulation indicate that the different columns of the PAG organize different coping strategies to pain and other stressors [62][63][64][65][66].…”

Neurobiology of apathy in Alzheimer's disease

“…Its role has been ascribed to a wide range of activities: conflict monitoring, error monitoring and detection 83,84 , response selection 85 , attention control 86 , pain affective processing 87,88 , social cognition 89 , reward probability processing 90 and autonomic activation 91 . The reason for the high number of proposed functions remains poorly understood.…”