Fibromyalgia Analog Model index analysis demonstrates the predictive validity of the Dahl S rat as a model of...

Animal models of disease are frequently used to test the safety and efficacy of new treatments and to explore mechanistic insights. The most useful models are those that accurately predict therapeutic success in humans of both pharmacologic and nonpharmacologic interventions. Here, we tested the predictive validity of the Dahl salt-sensitive (SS) rat strain as a model of fibromyalgia syndrome (FMS), a chronic disorder characterized by widespread musculoskeletal pain, fatigue, and mood disorders. Using the Fibromyalgia Analog Model (FAM) index, a multivariate statistical tool that quantifies the magnitude of fibromyalgia traits in an animal, we assessed the effectiveness of both established and investigational pharmacologic and nonpharmacologic therapies in SS rats. FAM scores were higher in female SS rats than males ( P < 0.0001), indicating more robust fibromyalgia-like traits, matching the higher prevalence of FMS in women. When compared to controls, treatments with the FDA-approved drugs for FMS milnacipran and pregabalin (both P < 0.0001, in males and females), as well as the investigational therapies metformin ( P < 0.0001) and green light exposure ( P = 0.0034 and P = 0.0002 for males and females, respectively) effectively decreased the FAM scores, showing reduction of FMS-like symptoms in SS rats. In contrast, indomethacin and the mu-opioid agonist DAMGO displayed limited efficacy ( P = 0.0239 and P = 0.0523, respectively), matching the relative effectiveness of these treatments in humans, justifying why they are not usually prescribed for patients with FMS. The results validate the SS rat as a predictive model in testing pharmacologic and nonpharmacologic therapies for FMS treatment, illustrating the utility of the FAM index in assessing treatment outcomes.