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

Authors

Cassie M. Argenbright, St. Jude Children’s Research Hospital
Ian F. Scully, University of Texas at Arlington
Damaris Flores, The University of Texas Rio Grande Valley
Perry N. Fuchs, The University of Texas Rio Grande Valley

Document Type

Article

Publication Date

7-3-2025

Abstract

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.

Comments

Original published version available at https://doi.org/10.1016/j.jpain.2025.105486

Recommended Citation

Argenbright, C. M., Scully, I. F., Flores, M. D., & Fuchs, P. N. (2025). A Multidimensional Preclinical Investigation of the Biogenic Amine Depletion and Subchronic Swim Models of Fibromyalgia. The Journal of Pain. https://doi.org/10.1016/j.jpain.2025.105486

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Publication Title

The Journal of Pain

DOI

10.1016/j.jpain.2025.105486