What Actually Causes Fibromyalgia? The Mitochondrial, Mast Cell, and Small Fiber Neuropathy Mechanisms Standard Treatment Misses — When drivers combine

Most fibromyalgia cases have features of more than one driver. The most common combinations: Driver 1 (mitochondrial) and Driver 2 (mast cell) frequently combine because the inflammation that activates mast cells also drives the CD38-NAD+ depletion that compromises mitochondrial function. Patients with this combination respond to both mitochondrial cofactor support and mast cell stabilization. Driver 2 (mast cell) and Driver 4 (gut-brain) frequently combine because Pattern A barrier-driven MCAS is mechanistically related to the gut barrier failure that drives systemic inflammation. Treatment addresses both layers concurrently. Driver 3 (small fiber neuropathy) often combines with Driver 1 (mitochondrial) because the small fibers are bioenergetically expensive and are among the first tissues to show functional compromise in mitochondrial states. Driver 4 (gut-brain) often combines with all the others because the systemic inflammatory tone affects mast cells, mitochondria, and small fibers simultaneously. The clinical task is to identify the dominant driver in the specific patient, name the contributing drivers, and sequence interventions accordingly.