Session Title: Fibromyalgia and Soft Tissue Disorders I
Session Type: Abstract Submissions (ACR)
Background/Purpose: Fibromyalgia (FM) is a chronic pain condition characterized by widespread musculoskeletal pain and a number of concomitant symptoms such as fatigue, sleep disturbance, cognitive dysfunction, anxiety, and depression. Milnacipran is a dual serotonin-norepinephrine reuptake inhibitor which has been shown to reduce pain and improve function in FM, however its clinical mechanism of action is largely unknown. Based on its neurotransmitter action in preclinical models, we hypothesized that milnacipran may decrease pain related brain activity in patients with FM.
Methods: 15 FM patients completed a randomized double-blind two-period cross-over study of milnacipran versus placebo. Each 7-week period (drug or placebo) was followed by a 14 day taper and washout. Prior to and following each period, fMRI scans were acquired for each patient. During the fMRI scanning session, pressure was applied to the patient’s thumbnail bed. Two pressure intensities were delivered to all subjects in a pseudo-random sequence. One pressure intensity was individually calibrated for each subject to elicit a perceived pain rating of approximately 50/100 (moderate pain). The other pressure intensity was held constant for all subjects at 1.5 kg/cm2. All fMRI data were pre-processed using SPM5. Regressors of interest (two pressure intensities) were convolved with the hemodynamic response function and applied to voxel-wise statistics. Images were then analyzed using a flexible factorial design within SPM5 to investigate changes in brain activations pre and post drug/placebo treatment. Regions of interest (ROIs) showing significant changes in blood-oxygen-level-dependent (BOLD) activation during either placebo or drug were extracted and analyzed using SPSS 19.
Results: During milnacipran treatment, FM patients displayed a significant reduction in pain-evoked BOLD activity within the right posterior and left mid-insula (post- minus pre- milnacipran percent BOLD change -0.727 ± 1.09 and -0.485 ± 0.837 respectively) and left inferior parietal lobule (IPL) (mean difference ± SD: -1.08 ± 1.27; all p<0.05 corrected). None of these changes were seen during treatment with placebo, and in fact an increase in insula BOLD activity during placebo was detected (0.707 ± 0.766 and 0.630 ± 0.581 respectively). The increase in right insula BOLD during placebo appeared to be due to incomplete washout of milnacipran during the cross-over as evidenced by decreased BOLD activity pre-placebo for those taking drug first (n=8; -0.651 ± 0.489; p<0.05). No significant correlations between changes in BOLD activation for any region and improvements in clinical pain were detected (all p>0.10).
Conclusion: Milnacipran reduces pain-evoked BOLD activity within the insula and IPL. Additionally; we find a sustained decrease in insular BOLD activation which persists following the removal of the drug. Although we did not detect a relationship with pain improvement in this small sample, larger samples may be needed to associate brain activity with the clinical mechanism of action of milnacipran. These findings have implications for randomized controlled trials of milnacipran in chronic pain populations.
A. E. Kairys,
R. E. Harris,
J. P. Hampson,
D. J. Clauw,
Pfizer Inc, Forest Laboratories, Merck, Nuvo ,
Pfizer, Forest, Lilly, Merck, Nuvo, J and J ,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/milnacipran-reduces-brain-activity-during-pain-in-fibromyalgia/