Molecular and functional PET-fMRI measures of placebo analgesia in episodic migraine: Preliminary findings

Linnman, Clas; Catana, Ciprian; Petkov, Mike P.; Chonde, Daniel B.; Becerra, Lino; Hooker, Jacob M.; Borsook, David

doi:10.1016/j.nicl.2017.11.011

Cited by 18 publications

(16 citation statements)

References 79 publications

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“…These findings are consistent with previous studies [39][40][41][42]. In fact, no difference in placebo analgesia responsiveness was reported between healthy controls and patients with low back pain [43], episodic migraine [44], irritable bowel syndrome [45], and atopic dermatitis patients [46]. Rating expectations has been suggested as a potential tool for predicting placebo responses [39].…”

Section: Discussionsupporting

confidence: 91%

Prior Therapeutic Experiences, Not Expectation Ratings, Predict Placebo Effects: An Experimental Study in Chronic Pain and Healthy Participants

Colloca

Akintola

Haycock

et al. 2020

Psychother Psychosom

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Introduction: Many clinical trials fail because of placebo responses. Prior therapeutic experiences and patients' expectations may affect the capacity to respond to placebos in chronic disorders. Objective: The scope of this study in 763 chronic orofacial pain and healthy study participants was to compare the magnitude and prevalence of placebo effects and determine the putative role of prior therapeutic experiences vs. expectations. Methods: We tested placebo propensity in a laboratory setting by using 2 distinct levels of individually tailored painful stimulations (high pain and low pain) to reinforce expectations and provide a hypoalgesic experience (conditioning phase). Afterwards, both levels of pain were surreptitiously set at a moderate pain level to test for placebo effects (testing phase). Pain and expectation ratings were assessed as primary outcomes using visual analog scales. Results: In both chronic pain and healthy participants, placebo effects were similar in magnitude, with the larger prevalence of responders in the healthy participants. Although chronic pain participants reported higher pain relief expectations, expectations did not account for the occurrence of placebo effects. Rather, prior experience via conditioning strength mediated placebo effects in both pain and healthy participants. Conclusions: These findings indicate that participants with chronic pain conditions display robust placebo effects that are not mediated by expectations but are instead directly linked to prior therapeutic experiences. This confirms the importance of assessing the therapeutic history while raising questions about the utility of expectation ratings. Future research is needed to enhance prediction of responses to placebos, which will ultimately improve clinical trial designs.

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Section: Discussionsupporting

confidence: 91%

Prior Therapeutic Experiences, Not Expectation Ratings, Predict Placebo Effects: An Experimental Study in Chronic Pain and Healthy Participants

Colloca

Akintola

Haycock

et al. 2020

Psychother Psychosom

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“…Moreover, patients with migraine and healthy controls did not differ regarding activity of opioid receptors induced by placebo. 34 As expected, few subjects from each group reported higher pain levels with the placebo treatment. Those individuals were classified as nocebo responders instead of placebo responders.…”

Section: Placebo-nocebo and The Opioid System: An Overview Of The supporting

confidence: 67%

“…30,61 Conversely, a recent PET study did not find differences in the availability of opioid receptors when comparing patients with episodic migraine and healthy subjects. 34 However, the lower sensibility of diprenorphine, 53 used to evaluate the functioning of the opioidergic system in that study along with the comparison at baseline conditions (eg, patients with migraine were scanned within their interictal phase), might explain their distinct results when compared with the previous studies. 16,45…”

Section: Changes In the Opioid System In Painful Syndromes And Chrmentioning

confidence: 91%

Positron emission tomography imaging of endogenous mu-opioid mechanisms during pain and migraine

DaSilva

Zubieta

DosSantos

2019

PR9

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The enormous advancements in the medical imaging methods witnessed in the past decades have allowed clinical researchers to study the function of the human brain in vivo, both in health and disease. In addition, a better understanding of brain responses to different modalities of stimuli such as pain, reward, or the administration of active or placebo interventions has been achieved through neuroimaging methods. Although magnetic resonance imaging has provided important information regarding structural, hemodynamic, and metabolic changes in the central nervous system related to pain, magnetic resonance imaging does not address modulatory pain systems at the molecular level (eg, endogenous opioid). Such important information has been obtained through positron emission tomography, bringing insights into the neuroplastic changes that occur in the context of the pain experience. Positron emission tomography studies have not only confirmed the brain structures involved in pain processing and modulation but also have helped elucidate the neural mechanisms that underlie healthy and pathological pain regulation. These data have shown some of the biological basis of the interindividual variability in pain perception and regulation. In addition, they provide crucial information to the mechanisms that drive placebo and nocebo effects, as well as represent an important source of variability in clinical trials. Positron emission tomography studies have also permitted exploration of the dynamic interaction between behavior and genetic factors and between different pain modulatory systems. This narrative review will present a summary of the main findings of the positron emission tomography studies that evaluated the functioning of the opioidergic system in the context of pain.

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“…104 In addition to pain, MOR is also believed to be involved in placebo analgesia and analgesic acupuncture. 103,107 However, no correlation between fMRI and PET signal changes was reported in two studies investigating placebo analgesia in healthy volunteers and patients with migraine. 103,107 A small cortical region in the orbital frontal cortex showed colocalized fMRI and PET signal changes (fMRI activation and reduction in PET binding potential as measured with [ 11 C]diprenorphine) to verum acupuncture but not placebo acupuncture.…”

Section: Pet/mri Of Endogenous Neurotransmitter Release By Pharmacolomentioning

confidence: 99%

Advances in simultaneous PET/MR for imaging neuroreceptor function

Sander

Hansen

Wey

2020

J Cereb Blood Flow Metab

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Hybrid imaging using PET/MRI has emerged as a platform for elucidating novel neurobiology, molecular and functional changes in disease, and responses to physiological or pharmacological interventions. For the central nervous system, PET/MRI has provided insights into biochemical processes, linking selective molecular targets and distributed brain function. This review highlights several examples that leverage the strengths of simultaneous PET/MRI, which includes measuring the perturbation of multi-modal imaging signals on dynamic timescales during pharmacological challenges, physiological interventions or behavioral tasks. We discuss important considerations for the experimental design of dynamic PET/MRI studies and data analysis approaches for comparing and quantifying simultaneous PET/MRI data. The primary focus of this review is on functional PET/MRI studies of neurotransmitter and receptor systems, with an emphasis on the dopamine, opioid, serotonin and glutamate systems as molecular neuromodulators. In this context, we provide an overview of studies that employ interventions to alter the activity of neuroreceptors or the release of neurotransmitters. Overall, we emphasize how the synergistic use of simultaneous PET/MRI with appropriate study design and interventions has the potential to expand our knowledge about the molecular and functional dynamics of the living human brain. Finally, we give an outlook on the future opportunities for simultaneous PET/MRI.

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Molecular and functional PET-fMRI measures of placebo analgesia in episodic migraine: Preliminary findings

Cited by 18 publications

References 79 publications

Prior Therapeutic Experiences, Not Expectation Ratings, Predict Placebo Effects: An Experimental Study in Chronic Pain and Healthy Participants

Prior Therapeutic Experiences, Not Expectation Ratings, Predict Placebo Effects: An Experimental Study in Chronic Pain and Healthy Participants

Positron emission tomography imaging of endogenous mu-opioid mechanisms during pain and migraine

Advances in simultaneous PET/MR for imaging neuroreceptor function

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