Characterization of the Dahl salt-sensitive rat as a rodent model of inherited, widespread, persistent pain
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".