A Multidimensional Preclinical Investigation of the Biogenic Amine Depletion and Subchronic Swim Models of Fibromyalgia.

Pain is a multidimensional phenomenon, encompassing affective-motivational, cognitive-evaluative, and sensory-discriminative domains. Understanding these components is crucial for effective diagnosis and management, particularly in conditions like fibromyalgia (FM), where pain is of unknown etiology. However, attempts to replicate FM through preclinical models often fail to replicate the disorder's multidimensionality. These studies evaluated the multidimensionality of two primary preclinical FM models-biogenic amine depletion(reserpine) and subchronic swim stress-across all three pain dimensions, and these models assessed predictive validity using the FDA-approved pharmacologic duloxetine (Cymbalta®). Additionally, the combinations of these models assessed whether their integration better mirrors clinical manifestations. The biogenic amine depletion model induced mechanical hyperalgesia and time-dependent thermal hyperalgesia, but it failed to replicate anxiety-like and depression-like behaviors. The subchronic swim stress model produced mechanical hyperalgesia, time-dependent thermal sensitivity, and trends in depression-like behavior, without impacting anxiety. The combined models exhibited mechanical and thermal sensitivities, along with anxiety-like behaviors and trending depression-like behaviors. However, all models were ineffective in influencing cognitive function. Duloxetine selectively decreased pain and depression-like behaviors but increased anxiety and induced lethargy. Future research should explore specific contexts where these models, individually or in combination, best replicate FM's clinical multidimensionality. PERSPECTIVE: In evaluating preclinical fibromyalgia models, this study finds that biogenic amine depletion and subchronic swim stress models replicate pain sensitivity, while their combination best reflects negative affect. However, neither model addresses cognitive deficits. This underscores the need for models that comprehensively replicate fibromyalgia's complex, multidimensional presentation for improved clinical relevance.