Highlights
- •A 6-week randomized controlled trial of milnacipran or placebo showed significant reduction in clinical fibromyalgia pain.
- •The magnitude of clinical pain reductions was not statistically different between milnacipran and placebo.
- •Mechanical and heat hyperalgesia predicted up to 80% of the variance in clinical fibromyalgia pain.
- •Fibromyalgia patients' hyperalgesia was strongly associated with their clinical pain.
Abstract
Milnacipran is a serotonin-norepinephrine reuptake inhibitor that was approved by
the U.S. Food and Drug Administration as effective therapy for fibromyalgia (FM) symptoms.
However, its analgesic mechanism of action is not well understood. We hypothesized
that improvement of mechanical and heat hyperalgesia would be a critical component
of overall milnacipran efficacy in FM. We used a novel quantitative sensory testing
protocol for assessment of mechanical and heat pain sensitivity that can be used for
testing of peripheral and central pain mechanisms and their impact on clinical pain
over time. We applied tonic mechanical and heat pain stimuli to 46 patients with FM
during a randomized controlled trial with either 50 mg milnacipran (n = 23) or placebo
(n = 23) twice daily over 6 weeks. During this trial, mean clinical pain (standard
deviation) was evaluated daily, and mechanical and heat pain sensitivity every 2 weeks.
At study entry, clinical pain was 5.0 (1.8) and 5.5 (1.8) visual analog scale units
for patients with FM randomized to placebo and milnacipran, respectively (P > .05). Over 6 weeks, clinical pain of patients with FM significantly declined by
15%, but this improvement was not statistically different between milnacipran and
placebo. However, repeated measures of mechanical and heat pain sensitivity reliably
predicted up to 80% of the variance in clinical FM pain at every time point. Clinical
pain and mechanical/heat pain sensitivity of patients with FM steadily declined during
this trial, but the effects of milnacipran were not found to be superior to placebo.
Repeated measures of mechanical/heat hyperalgesia reliably predicted large amounts
of the variance in clinical pain across all participants, indicating their relevance
for FM pain.
Perspective
Although clinical pain and hyperalgesia decreased during this 6-week trial, the efficacy
of milnacipran was not superior to placebo. The high correlations between clinical
pain and hyperalgesia ratings at every time point seem to emphasize the relevant contributions
of mechanical and heat hyperalgesia to clinical FM pain.
Key words
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Article info
Publication history
Published online: May 18, 2015
Accepted:
April 30,
2015
Received in revised form:
April 19,
2015
Received:
January 12,
2015
Footnotes
Clinicaltrials.gov Id: NCT01294059.
This study was supported by an investigator-initiated grant from Forest Laboratories. All study drugs were provided by Forest Laboratories. The sponsors of this trial had no role in planning and implementing the study or in the analysis of the data. They were not involved in the writing of this report. None of the authors has any financial or other relationships that might lead to a conflict of interest.
Identification
Copyright
© 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.
