Characterization of the Dahl salt-sensitive rat as a rodent model of inherited, widespread, persistent pain
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 me...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-24094-9 |
| _version_ | 1797988470714531840 |
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| author | Luiz F. Ferrari Charles Rey Anna Ramirez Adam Dziuba Jacqueline Zickella Michael Zickella Hershel Raff Norman E. Taylor |
| author_facet | Luiz F. Ferrari Charles Rey Anna Ramirez Adam Dziuba Jacqueline Zickella Michael Zickella Hershel Raff Norman E. Taylor |
| author_sort | Luiz F. Ferrari |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T08:03:23Z |
| format | Article |
| id | doaj.art-2c3d769cab1a4ba1a9894451c9b54919 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T08:03:23Z |
| publishDate | 2022-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-2c3d769cab1a4ba1a9894451c9b549192022-12-22T04:35:37ZengNature PortfolioScientific Reports2045-23222022-11-0112111610.1038/s41598-022-24094-9Characterization of the Dahl salt-sensitive rat as a rodent model of inherited, widespread, persistent painLuiz F. Ferrari0Charles Rey1Anna Ramirez2Adam Dziuba3Jacqueline Zickella4Michael Zickella5Hershel Raff6Norman E. Taylor7Department of Anesthesiology, University of Utah School of MedicineDepartment of Anesthesiology, University of Utah School of MedicineDepartment of Anesthesiology, University of Utah School of MedicineDepartment of Anesthesiology, University of Utah School of MedicineDepartment of Anesthesiology, University of Utah School of MedicineDepartment of Anesthesiology, University of Utah School of MedicineEndocrine Research Laboratory, Aurora St. Luke’s Medical Center, Advocate Aurora Research InstituteDepartment of Anesthesiology, University of Utah School of MedicineAbstract 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.https://doi.org/10.1038/s41598-022-24094-9 |
| spellingShingle | Luiz F. Ferrari Charles Rey Anna Ramirez Adam Dziuba Jacqueline Zickella Michael Zickella Hershel Raff Norman E. Taylor Characterization of the Dahl salt-sensitive rat as a rodent model of inherited, widespread, persistent pain Scientific Reports |
| title | Characterization of the Dahl salt-sensitive rat as a rodent model of inherited, widespread, persistent pain |
| title_full | Characterization of the Dahl salt-sensitive rat as a rodent model of inherited, widespread, persistent pain |
| title_fullStr | Characterization of the Dahl salt-sensitive rat as a rodent model of inherited, widespread, persistent pain |
| title_full_unstemmed | Characterization of the Dahl salt-sensitive rat as a rodent model of inherited, widespread, persistent pain |
| title_short | Characterization of the Dahl salt-sensitive rat as a rodent model of inherited, widespread, persistent pain |
| title_sort | characterization of the dahl salt sensitive rat as a rodent model of inherited widespread persistent pain |
| url | https://doi.org/10.1038/s41598-022-24094-9 |
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