Milnacipran is a selective serotonin-norepinephrine reuptake inhibitor (SNRI). No studies have examined the effect of SNRIs on pain in RA. However, several studies have examined the role of SNRIs in fibromyalgia and related pain conditions. Treatment with milnacipran has been associated with improvements in clinical pain severity in Phase 2 and Phase 3 randomized placebo-controlled trials of fibromyalgia patients. In animal models, milnacipran appears to moderate the pain-inducing effects of inflammation and central sensitization. Thus milnacipran may be an ideal drug to treat pain in RA.