Fibromyalgia

What changes during this transition

Fibromyalgia is a defined clinical disorder under the ACR 2010 / 2016 criteria — widespread pain index ≥7 plus symptom severity scale ≥5 (or WPI 3-6 plus SSS ≥9), symptoms present at similar level for ≥3 months, no other disorder accounting for the pain. The pathophysiology is central sensitization driven by altered descending pain-modulation pathways, not peripheral nociception; this is the load-bearing framing that distinguishes FM from inflammatory or mechanical pain syndromes and determines what does (and does not) work as treatment. Standard-of-care is layered and well-evidenced. FDA-approved pharmacotherapy: duloxetine (Cymbalta, approved 2008), milnacipran (Savella, approved 2009), and pregabalin (Lyrica, approved 2007) are the FDA-approved FM trio. Off-label guideline-supported: amitriptyline (the longest-standing pharmacological intervention), gabapentin, cyclobenzaprine, and the emerging low-dose-naltrexone (LDN) at 1-4.5 mg with the Younger 2009 and Younger 2013 trial signals supporting it. Non-pharmacological Tier 1: cognitive behavioral therapy and graded aerobic exercise both carry EULAR 2017 Tier 1 evidence and outrank any pharmacotherapy on long-term functional outcomes. Sleep workup is non-optional given the unrefreshing sleep that's part of the symptom-severity criteria — sleep apnea screening (STOP-BANG, polysomnography if indicated) is the precondition because untreated OSA mimics FM-sleep symptoms. The peptide library's role on this axis is narrow and editorially specific. Selank (Tier 3 surfaced) addresses the anxiety overlay — generalized anxiety disorder runs 30-50% comorbid in FM cohorts, the Russian Ministry of Health 2009 registration is for GAD + neurasthenia, and the benzodiazepine-sparing context is editorially relevant in a population that carries elevated chronic-benzo prescribing from years of inadequately-addressed sleep and hyperarousal symptoms. Zozulya 2008 head-to-head against medazepam (n=62) anchors the comparison. The Selank case is the anxiety + autonomic-hyperarousal overlay specifically, NOT the central-sensitization pain biology itself — and that distinction is the editorial honesty this trigger demands. B12-methylcobalamin (Tier 2 surfaced) is the rule-out before SNRI / pregabalin / amitriptyline escalation — published cohorts report elevated rates of functional B12 deficiency in FM patients (chronic-PPI users, long-term metformin users, strict vegans, post-bariatric patients, elderly with atrophic gastritis are the high-prevalence subgroups), and the Regland 2015 PLoS ONE Swedish ME/CFS + FM cohort with methylcobalamin + folate combination is the load-bearing evidence anchor. MMA + homocysteine are the load-bearing markers — serum B12 is unreliable in the gray zone. What is NOT surfaced and why. Oxytocin is substrate-only — the mechanism story for central pain processing is real but the empirical signal is thin (Mameli n=14 null result is the largest published FM trial; community framing runs ahead of evidence; the Leng / Ludwig 2016 intranasal-bioavailability critique haunts the route). BPC-157 is substrate-only — community framing extrapolates rodent gut-vagal-axis work to a central-sensitization disorder that BPC's research corpus never engaged; the Boban-Blagaic 2006 morphine-analgesia-counteraction signal is the load-bearing safety thread for the FM subset still on chronic opioids; WADA S0 status is a hard regulatory stop for tested athletes. DSIP is substrate-only — the entire clinical evidence base is 1980s small trials in chronic-insomnia and addiction-withdrawal cohorts, no FM-specific trial in any jurisdiction.