Background/Purpose:
Previous studies indicate that fibromyalgia (FM) patients have augmented clinical and brain responses to painful stimuli (i.e. hyperalgesia/allodynia), as well as increased production of endogenous opioids, and reduced μ-opioid receptor (MOR) binding. However, it is not known if these factors co-occur within the same individual or if these factors act independently. We performed a longitudinal investigation using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) in chronic pain patients diagnosed with FM to address this question. If these factors operate in the same individual, we expected an inverse correlation between changes in fMRI evoked pain activity and MOR binding potential (BP).
Methods:
fMRI and PET imaging sessions were performed on 18 female opioid-naïve FM patients (age 45.4+/- 13.0). Each participant underwent 4 weeks of non-pharmacological treatment. Before and after treatment, each patient underwent an fMRI scan with varying levels of pressure pain applied to the thumb as well as a 90-minute [11C]carfentanil PET scan under resting conditions. After quantification of the PET data with Logan plots, fMRI images and preprocessing of PET data were performed with statistical parametric mapping (SPM5). fMRI and PET scans were normalized to the same template. Difference images before and after treatment were calculated for both the fMRI contrast and PET images. A whole-brain voxel-by-voxel correlation analysis between the fMRI and PET difference images were carried out using the Biological Parametric Mapping toolbox. Activation clusters were defined based on a correlation coefficient, with |R|>=0.6 uncorrected. Clinical pain was assessed with Short Form McGill Pain Questionnaire (SFMPQ).
Results:
Negative correlations between the change in the fMRI blood oxygenation level dependent (BOLD) signal and MOR BP were observed in multiple regions involved in pain processing and modulation: right posterior insula R=-0.82,P=0.0004; left medial insula R=-0.82, P=0.0003; left orbital frontal cortex R=-0.75, P=0.0004; right amygdala R=-0.68, P=0.002; brainstem R=-0.71, P=0.0009. Positive correlations were observed in right DLPFC R=0.66, P=0.003; posterior cingulate R=0.62, P=0.006; right putamen R=0.72, P=0.0008. Changes in both functional imaging outcomes were negatively associated with changes in clinical pain: BOLD in right DLPFC and clinical pain SFMPQ; R=-0.52, P=0.03; MOR BP in left medial insula and SFMPQ present pain R=-0.51, P=0.03.
Conclusion:
We find strong longitudinal associations between evoked pain activations suggestive of hyperalgesia, and µ-opioid receptor availability (binding potential, BP) within the same brain regions, in individual FM patients. Positive associations were also observed between BOLD responses, and μ-opioid receptor BP (in opposive directions) with respect to clinical pain. These data suggest that the µ-opioid system is somehow involved in the pathogenesis of FM, and may even help explain why these patients are generally not felt to respond to narcotic analgesics, and may even be made worse when these drugs are used therapeutically.
Disclosure:
H. Wang,
None;
D. J. Clauw,
Pfizer Inc, Forest Laboratories, Merck, Nuvo ,
2,
Pfizer, Forest, Lilly, Merck, Nuvo, J and J ,
5;
J. K. Zubieta,
None;
R. E. Harris,
Pfizer Inc,
2,
Pfizer Inc,
5.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/evoked-pain-brain-response-is-associated-with-reduced-%ce%bc-opioid-receptor-binding-in-fibromyalgia/