<p>Dual-Acting Peripherally Restricted Delta/Kappa Opioid (CAV1001) Produces Antinociception in Animal Models of Sub-Acute and Chronic Pain</p>
Bibliographic record
Abstract
BACKGROUND: The development of highly efficacious alternatives to mu-opioid analgesics represents an urgent unmet medical and public health need. In the presence of inflammation both delta- and kappa-opioid agonists, acting on peripheral sensory neurons, mediate analgesia. The dual-acting, peripherally restricted kappa/delta-opioid agonist, CAV1001, was tested in four rodent pain models. METHODS: Experiment 1 - Formalin testing in mice. Three doses (1-10 mg/kg) of CAV1001 or ICI204448 at 30 minutes were tested after formalin injection. Spontaneous nocifensive responses were video recorded. Experiment 2 - Complete Freund's Adjuvant (CFA)-induced arthritis. CFA was injected into the ankle joint of rats. Joint compression thresholds (JCT) were measured. CAV1001 was compared to celecoxib. Experiment 3 - Spinal nerve ligation (SNL) in rats. Paw compression thresholds (PCT) were measured. CAV1001 was compared to gabapentin. Experiment 4 - MMRT-1 bone cancer implantation into the rat tibia. Weight-bearing was assessed. CAV1001 was compared to morphine. RESULTS: In Phase 2 of the formalin model, CAV1001 (1 mg/kg) significantly reduced pain behaviors to a degree comparable to the peripherally restricted kappa-opioid agonist, ICI204448 (10 mg/kg). CAV1001 (10 mg/kg) effectively eliminated pain behaviors associated with phase 2. In the CFA-induced arthritis model, a significant increase in JCTs, similar to the comparator celecoxib, was observed with CAV1001 at 1 mg/kg at 2 hours; CAV1001 (10 mg/kg) was effective at 1 hour. In the SNL model, both the comparator gabapentin and CAV1001 (5 mg/kg) significantly reduced PCT at 2 hours, but at 4 hours, the CAV1001 thresholds improved to baseline. CAV1001 10 mg/kg significantly improved weight bearing at 4-hour post-dosing compared to baseline following MMRT-1 implantation. CONCLUSION: CAV1001 demonstrated efficacy in several different preclinical pain models. Time- and dose-dependent differences in the efficacy of CAV1001 amongst these rodent pain models parallel the degree of underlying inflammation.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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".