Topically Administered Ketamine Reduces Capsaicin-Evoked Mechanical Hyperalgesia
Bibliographic record
Abstract
BACKGROUND: The n-methyl-d-aspartate receptor antagonists such as ketamine relieve chronic pain but their oral and parenteral use is limited by the adverse effects. Experimental studies indicate that the peripheral n-methyl-d-aspartate receptors are involved in nociception. Recent clinical findings suggest that ketamine gel alleviates neuropathic pain, but no placebo-controlled randomized studies are available on the neurosensory effects of ketamine gel in experimental neurogenic pain. OBJECTIVES: The aim of this study was to assess the effects of topically applied ketamine using the intradermal capsaicin model in healthy volunteers. METHODS: Nine healthy subjects received ketamine and placebo gel on 3 occasions in a randomized, double-blind, and crossover manner. The concentration of ketamine was 50 mg/mL. One milliliter of gel was rubbed into the skin of both forearms 10 minutes before the intradermal injection of capsaicin (250 microg). Thereafter, the intensity and unpleasantness of spontaneous and evoked pain and dysesthesia was assessed up to 60 minutes using a 10-cm visual analog scale. Pain and dysesthesia were evoked using cotton gauze, a von Frey microfilament, and 38 degrees C, 42 degrees C, and 47 degrees C heat. Side effects were recorded, and individuals' subjective experiences were assessed with a standard questionnaire. RESULTS: Ketamine gel had no effect on immediate burning pain followed by the capsaicin injection. Both the intensity and unpleasantness of mechanical hyperalgesia was statistically significantly reduced by ketamine gel applied both on the left and right side. Neither tactile allodynia evoked by a brush nor thermal hyperalgesia were observed in any volunteer. No local or systemic side effects were observed. No patient reported any drug effects. DISCUSSION: A significant reduction of mechanical hyperalgesia was produced by topically and pre-emptively applied ketamine in healthy patients. We propose that the mechanism of action would be the reduction of central sensitization caused by the absorption of ketamine in circulation.
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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 | 0.001 |
| 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) | 0.002 | 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".