Dysregulation of Cellular Calcium Homeostasis in Chemotherapy-Evoked Painful Peripheral Neuropathy
Bibliographic record
Abstract
In Brief Paclitaxel and vincristine are chemotherapeutic drugs that often evoke a long-lasting painful peripheral neuropathy. Using drugs that reduce intracellular or extracellular calcium ions (Ca2+), we investigated the hypothesis that impaired Ca2+ regulation contributes to the chemotherapy-evoked neuropathic pain syndrome. For comparison, we also tested rats with painful peripheral neuropathy caused by nerve trauma and to the anti-human immunodeficiency virus nucleoside analog 2′,3′-dideoxycytidine (ddC). Normal naïve (without neuropathy), paclitaxel-treated, and vincristine-treated rats received the following intrathecal injections: TMB-8 (46 nmol), Quin-2 (1.8 nmol), EGTA (0.1 μmol), EGTA-am (0.1 μmol), and their vehicle controls. Chronic constriction injury (CCI) rats were examined after TMB-8 and Quin-2 injections, and ddC-treated rats were examined after receiving TMB-8. Mechano-allodynia and mechano-hyperalgesia were evaluated after each injection. Drug effects on heat hyperalgesia were also tested in CCI rats. All four Ca2+-reducing drugs significantly inhibited mechano-allodynia and mechano-hyperalgesia in the rats treated with paclitaxel, vincristine, or ddC, but no effects were seen in the CCI or naïve rats. We conclude that a similar abnormality of cellular Ca2+ homeostasis contributes to the pain caused by paclitaxel, vincristine, and ddC, but not posttraumatic painful peripheral neuropathy. IMPLICATIONS: Paclitaxel and vincristine often produce a pain syndrome that compromises their usefulness as anticancer drugs. The experiments described here suggest that the pain may be caused by an impairment of neuronal or glial ability to properly regulate intracellular Ca2+. A possible underlying pathology could be impaired mitochondrial Ca2+ regulation.
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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".