fibromyalgia
Fibromyalgia is a central sensitization syndrome characterized by widespread musculoskeletal pain, fatigue, sleep disturbance, and cognitive difficulty ("fibro fog"), affecting approximately 2–4% of the global population, predominantly women. The pathophysiology involves abnormal central pain processing — amplified pain signals due to dysregulation of neurotransmitter systems including serotonin, norepinephrine, and substance P — rather than peripheral inflammation or tissue damage, distinguishing fibromyalgia from inflammatory arthritis or neuropathy.
Active trials investigate low-dose naltrexone for neuroinflammation, cannabidiol and endocannabinoid-targeting approaches, transcranial direct current stimulation (tDCS), mindfulness-based cognitive therapy combined with pharmacotherapy, milnacipran analogs with improved tolerability, and patient-reported digital biomarkers using actigraphy and ecological momentary assessment. Sleep intervention trials addressing the relationship between restorative sleep and pain amplification are an emerging area.
Fibromyalgia trials use the ACR 2010/2016 diagnostic criteria and require a minimum pain intensity score on a 0–10 NRS; previous failure of at least one FDA-approved therapy (pregabalin, duloxetine, or milnacipran) is required for most third-line trials.