Effects of mitochondrial poisons on the neuropathic pain produced by the chemotherapeutic agents, paclitaxel and oxaliplatin
Bibliographic record
Abstract
The dose-limiting side effect of taxane, platinum-complex, and other kinds of anticancer drugs is a chronic, distal, bilaterally symmetrical, sensory peripheral neuropathy that is often accompanied by neuropathic pain. Work with animal models of these conditions suggests that the neuropathy is a consequence of toxic effects on mitochondria in primary afferent sensory neurons. If this is true, then additional mitochondrial insult ought to make the neuropathic pain worse. This prediction was tested in rats with painful peripheral neuropathy due to the taxane agent, paclitaxel, and the platinum-complex agent, oxaliplatin. Rats with established neuropathy were given 1 of 3 mitochondrial poisons: rotenone (an inhibitor of respiratory Complex I), oligomycin (an inhibitor of adenosine triphosphate synthase), and auranofin (an inhibitor of the thioredoxin-thioredoxin reductase mitochondrial antioxidant defense system). All 3 toxins significantly increased the severity of paclitaxel-evoked and oxaliplatin-evoked mechano-allodynia and mechano-hyperalgesia while having no effect on the mechano-sensitivity of chemotherapy-naïve rats. Chemotherapy-evoked painful peripheral neuropathy is associated with an abnormal spontaneous discharge in primary afferent A fibers and C fibers. Oligomycin, at the same dose that exacerbated allodynia and hyperalgesia, significantly increased the discharge frequency of spontaneously discharging A fibers and C fibers in both paclitaxel-treated and oxaliplatin-treated rats, but did not evoke any discharge in naïve control rats. These results implicate mitochondrial dysfunction in the production of chemotherapy-evoked neuropathic pain and suggest that drugs that have positive effects on mitochondrial function may be of use in its treatment and prevention.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".