Placebo effects on human μ-opioid activity during pain

Department of Psychology, Columbia University, 1190 Amsterdam Avenue, New York, NY 10027, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 07/2007; 104(26):11056-61. DOI: 10.1073/pnas.0702413104
Source: PubMed

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 mu-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 mu-opioid receptor-rich 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 placebo-induced 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.

Download full-text


Available from: David Scott, Jul 06, 2015
1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To determine if overnight tobacco abstinent carriers of the AG or GG (*G) vs. the AA variant of the human mu opioid receptor (OPRM1) A118G polymorphism (rs1799971) differ in [(11)C]carfentanil binding after tobacco smoking. Twenty healthy American male smokers who abstained from tobacco overnight were genotyped and completed positron emission tomography (PET) scans with the mu opioid receptor agonist, [(11)C]carfentanil. They smoked deniconized (denic) and average nicotine (avnic) cigarettes during the PET scans. Smoking avnic cigarette decreased the binding potential (BPND) of [(11)C]carfentanil in the right medial prefrontal cortex (mPfc; 6,56,18), left anterior medial prefrontal cortex (amPfc; -2,46,44), right ventral striatum (vStr; 16, 3, -10), left insula (Ins; -42,10,-12), right hippocampus (Hippo; 18,-6,-14) and left cerebellum (Cbl; -10,-88,-34), and increased the BPND in left amygdala (Amy; -20,0,-22), left putamen (Put; -22, 10,-6) and left nucleus accumbens (NAcc; -10,12,-8). In the AA allele carriers, avnic cigarette smoking significantly changed the BPND compared to after denic smoking in most brain areas listed above. However in the *G carriers the significant BPND changes were confirmed in only amPfc and vStr. Free mu opioid receptor availability was significantly less in the *G than the AA carriers in the Amy and NAcc. The present study demonstrates BPND changes induced by avnic smoking in OPRM1 *G carriers were blunted compared to the AA carriers. Also *G smokers had less free mu opioid receptor availability in Amy and NAcc. Copyright © 2015. Published by Elsevier Inc.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 01/2015; 59. DOI:10.1016/j.pnpbp.2015.01.007 · 4.03 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: People feel bad for inflicting harms upon others; this emotional state is termed interpersonal guilt. In this study, the participant played multiple rounds of a dot-estimation task with anonymous partners while undergoing fMRI. The partner would receive pain stimulation if the partner or the participant or both responded incorrectly; the participant was then given the option to intervene and bear a proportion of pain for the partner. The level of pain voluntarily taken and the activations in anterior middle cingulate cortex (aMCC) and bilateral anterior insula (AI) were higher when the participant was solely responsible for the stimulation (Self_Incorrect) than when both committed an error (Both_Incorrect). Moreover, the gray matter volume in the aMCC predicted the individual's compensation behavior, measured as the difference between the level of pain taken in the Self_Incorrect and Both_Incorrect conditions. Furthermore, a mediation pathway analysis revealed that activation in a midbrain region mediated the relationship between aMCC activation and the individual's tendency to compensate. These results demonstrate that the aMCC and the midbrain nucleus not only play an important role in experiencing interpersonal guilt, but also contribute to compensation behavior.
    Social Cognitive and Affective Neuroscience 08/2014; 9(8):1150-1158. DOI:10.1093/scan/nst090 · 5.88 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Individuals undergoing treatment for a symptom like pain expect that the treatment will reduce the pain. Many studies show that healthy volunteers or patients in pain report less pain after inactive treatment, if they believe that active medication has been administrated. The reduction of pain can be partly blocked by systemic administration of naloxone, an opioid antagonist. There is reduced central nervous system activation to painful stimuli in individuals who have been given a placebo and told it is a painkiller. These findings suggest that the expectation of pain relief generates central nervous system opioid activity that inhibits pain transmission to the cerebral cortex. Expectations may thus lead to changes in central nervous system activity that reduces pain. It is proposed that expectations activate a homeostatic system that corrects perturbations to the system via negative feedback. The nocebo effect is the opposite of the placebo effect, and is due to induction of negative emotions. Part of the treatment of many symptoms and diseases is due to autonomic adjustments controlled by the central nervous system. The involvement of emotional processes in placebo effects could have important consequences for interpretation of data from randomized controlled trials.
    Handbook of experimental pharmacology 01/2014; 225:81-96. DOI:10.1007/978-3-662-44519-8_5