Session Information
Session Title: Pain: Basic and Clinical Aspects
Session Type: Abstract Submissions (ACR)
Background/Purpose: Clinical trials have shown that serotonin norepinephrine reuptake inhibitors, such as milnacipran, decrease pain in chronic non-inflammatory pain conditions like fibromyalgia and osteoarthritis. We examined the effect of milnacipran on self-reported pain intensity and experimental pain sensitivity among rheumatoid arthritis (RA) patients with widespread pain on a stable treatment regimen.
Methods: Thirty-two subjects with RA completed a double-blind, crossover study. Subjects were randomized to receive milnacipran 50 mg twice daily or placebo for 6 weeks, followed by a 3-week washout and crossed over to the other arm for the remaining 6 weeks. Subjects completed the Brief Pain Inventory – short form (BPI-sf) to assess self-reported pain intensity and the Symptom Intensity Scale (SIS) to assess symptoms of fibromyalgia. Subjects also underwent quantitative assessments of pressure pain thresholds at joint and non-joint sites, using a Wagner FPK 20 algometer. Pain thresholds at the trapezius were measured before and after a noxious conditioning stimulus to assess conditioned pain modulation, a measure of the descending analgesic pain pathways. The primary outcome was change in self-reported pain, measured by the BPI-sf average pain intensity. Secondary outcomes included changes in the SIS score, pain thresholds and conditioned pain modulation. Changes in pain measures were compared between milnacipran and placebo using Wilcoxon signed rank tests and linear mixed models.
Results: After 6 weeks of milnacipran, BPI-sf average pain intensity decreased 0.7 (SD 1.7) points on a 0-10 scale, compared to a decrease of 0.3 (SD 2.0) after 6 weeks of placebo (P = 0.37) (Table). Thumbnail pressure pain threshold increased by 0.7 (SD 1.4) during milnacipran treatment compared to -0.02 (SD 1.4) during placebo (P = 0.04). None of the other secondary outcome measures differed significantly between treatment periods. In the subgroup of subjects with swollen joint count less than or equal to 1, BPI-sf average pain intensity decreased 1.0 (SD 1.6) points, compared to an increase of 0.1 (SD 1.9) during placebo (P = 0.04). In this subgroup, the increase in thumbnail pressure pain threshold was also significantly higher during milnacipran treatment compared to placebo (P = 0.003).
Conclusion: This randomized, blinded cross-over trial of milnacipran vs. placebo revealed no overall differences in improvements in pain intensity, fibromyalgia symptoms and experimentally assessed pain measures. Subgroup analyses among patients with 0-1 swollen joints suggested that milnacipran may have a role in diminishing overall pain among RA patients who have minimal evidence of inflammatory disease activity. This finding needs to be replicated in a larger study, designed specifically to examine the effects of milnacipran among RA patients in remission or with low disease activity.
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Table: Means (standard deviations) for measures of pain
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Placebo
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Milnacipran
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P-values
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Baseline
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6-weeks
|
Change
|
Baseline
|
6-weeks
|
Change
|
Unadjustedb
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Adjustedc
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|
|
BPI-sf Average Pain Intensitya |
5.2 (2.1) |
4.9 (2.1) |
-0.3 (2.0) |
5.6 (2.0) |
4.8 (2.2) |
-0.7 (1.7) |
0.42 |
0.37 |
|
Symptom Intensity Scale |
5.1 (2.1) |
4.3 (2.4) |
-0.8 (1.9) |
5.2 (2.0) |
4.5 (8.3) |
-0.7 (1.6) |
0.89 |
0.83 |
|
Thumbnail Pain Threshold |
5.8 (3.0) |
5.8 (2.8) |
-0.02 (1.4) |
5.3 (2.7) |
6.0 (2.8) |
0.7 (1.4) |
0.04
|
0.04
|
|
Trapezius Pain Threshold |
4.9 (2.8) |
5.5 (3.1) |
0.6 (1.5) |
5.1 (3.1) |
5.5 (3.1) |
0.4 (1.3) |
0.89 |
0.44 |
|
Wrist Pain Threshold |
5.3 (2.7) |
5.9 (3.0) |
0.6 (1.6) |
5.0 (2.4) |
5.9 (2.9) |
0.9 (1.5) |
0.35 |
0.34 |
|
Knee Pain Threshold |
7.0 (3.1) |
7.3 (3.1) |
0.3 (1.8) |
6.9 (3.2) |
7.3 (3.2) |
0.3 (1.4) |
0.72 |
0.82 |
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Conditioned Pain Modulation |
0.8 (1.0) |
0.9 (1.3) |
0.1 (1.2) |
0.8 (1.1) |
0.9 (1.1) |
0.1 (1.5) |
0.39 |
0.96 |
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Abbreviations: BPI-sf, Brief Pain Inventory – short form. a Based on a 0-10 scale with 10 being worse pain. b P-values for the difference between the values during milnacipran vs. placebo using Wilcoxon signed-rank tests. c P-values for the difference between the values during milnacipran vs. placebo using linear mixed models including treatment, crossover period and treatment sequence. |
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Disclosure:
Y. C. Lee,
Forest Research Institute,
2,
Merck Pharmaceuticals,
1,
Cubist Pharmaceuticals,
1,
Perrigo,
1,
Express Scripts,
1;
E. Massarotti,
Amplimmune,
5,
Alexion Pharmaceuticals, Inc.,
5,
Human Genome Sciences, Inc.,
2,
Bristol Myers Squibb,
2,
Sanofi-Aventis Pharmaceutical,
2;
R. R. Edwards,
None;
B. Lu,
None;
C. C. Liu,
None;
Y. Lo,
None;
A. Wohlfahrt,
None;
N. Kim,
None;
D. J. Clauw,
None;
D. H. Solomon,
Pfizer Inc,
2,
Amgen,
2,
Lilly,
2,
Corrona,
2,
UpToDate,
7.
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