Characterization of the Dahl salt-sensitive rat as a rodent model of inherited, widespread, persistent pain

Authors

Luiz F. Ferrari, Department of Anesthesiology, University of Utah School of Medicine, 383 Colorow Drive, Salt Lake City, UT, 84108, USA.
Charles Rey, Department of Anesthesiology, University of Utah School of Medicine, 383 Colorow Drive, Salt Lake City, UT, 84108, USA.
Anna Ramirez, Department of Anesthesiology, University of Utah School of Medicine, 383 Colorow Drive, Salt Lake City, UT, 84108, USA.
Adam Dziuba, Department of Anesthesiology, University of Utah School of Medicine, 383 Colorow Drive, Salt Lake City, UT, 84108, USA.
Jacqueline Zickella, Department of Anesthesiology, University of Utah School of Medicine, 383 Colorow Drive, Salt Lake City, UT, 84108, USA.
Michael Zickella, Department of Anesthesiology, University of Utah School of Medicine, 383 Colorow Drive, Salt Lake City, UT, 84108, USA.
Hershel Raff, Advocate Aurora HealthFollow
Norman E. Taylor, Department of Anesthesiology, University of Utah School of Medicine, 383 Colorow Drive, Salt Lake City, UT, 84108, USA. norman.taylor@hsc.utah.edu.

Recommended Citation

Ferrari LF, Rey C, Ramirez A, et al. Characterization of the Dahl salt-sensitive rat as a rodent model of inherited, widespread, persistent pain. Sci Rep. 2022;12(1):19348. Published 2022 Nov 11. doi:10.1038/s41598-022-24094-9

Affiliations

Advocate Aurora Research Institute

Abstract

Animal models are essential for studying the pathophysiology of chronic pain disorders and as screening tools for new therapies. However, most models available do not reproduce key characteristics of clinical persistent pain. This has limited their ability to accurately predict which new medicines will be clinically effective. Here, we characterize the Dahl salt-sensitive (SS) rat strain as the first rodent model of inherited widespread hyperalgesia. We show that this strain exhibits physiological phenotypes known to contribute to chronic pain, such as neuroinflammation, defective endogenous pain modulation, dysfunctional hypothalamic-pituitary-adrenal axis, increased oxidative stress and immune cell activation. When compared with Sprague Dawley and Brown Norway rats, SS rats have lower nociceptive thresholds due to increased inflammatory mediator concentrations, lower corticosterone levels, and high oxidative stress. Treatment with dexamethasone, the reactive oxygen species scavenger tempol, or the glial inhibitor minocycline attenuated the pain sensitivity in SS rats without affecting the other strains while indomethacin and gabapentin provided less robust pain relief. Moreover, SS rats presented impaired diffuse noxious inhibitory controls and an exacerbated response to the proalgesic mediator PGE₂, features of generalized pain conditions. These data establish this strain as a novel model of spontaneous, widespread hyperalgesia that can be used to identify biomarkers for chronic pain diagnosis and treatment.

Document Type

Article

PubMed ID

36369350