Natelson, Benjamin H, Vu, Diana, Mao, Xiangling et al. · The journal of pain · 2015 · DOI
This study tested whether a medication called milnacipran could reduce brain inflammation and pain in fibromyalgia patients. Researchers measured a chemical called lactate in the brain using a special MRI scan and found that fibromyalgia patients had higher levels than healthy people. After 8 weeks of treatment, patients taking milnacipran showed lower lactate levels and less pain compared to those taking placebo, suggesting the medication may work by reducing brain inflammation.
This study is significant because it identifies a potential biological marker (ventricular lactate) for central inflammation in chronic pain conditions and demonstrates that a currently-approved medication can reduce both this marker and symptoms. For ME/CFS patients and researchers, it supports the hypothesis that elevated lactate may indicate neuroinflammation in post-exertional malaise and other central nervous system symptoms, opening possibilities for targeting similar pathways.
This study does not prove that milnacipran is effective for ME/CFS, as it examined only fibromyalgia patients—a different diagnosis with overlapping but distinct pathophysiology. It also does not establish that lactate reduction directly causes pain improvement (correlation does not prove causation), and the fact that lactate remained elevated after treatment raises questions about whether this biomarker fully explains therapeutic response. The lack of cognitive improvement despite lactate reduction suggests the mechanism may be more complex than initially hypothesized.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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