Chronic Oral Gabapentin Reduces Elements of Central Sensitization in Human Experimental Hyperalgesia
Bibliographic record
Abstract
BACKGROUND: In chronic pain, increased activity from intact or damaged peripheral nerve endings results in an enhanced response in central pain transmission systems, a mechanism known as central sensitization. Central sensitization can also be invoked in human experimental models. Therefore, these models may be useful to characterize novel analgesics in humans. The anticonvulsant gabapentin has demonstrated efficacy in patients with neuropathic pain, but its mode of action remains unclear. This study examined the effects of gabapentin on signs of central sensitization (brush and pinprick hyperalgesia) in a human model of capsaicin-evoked pain, using a gabapentin dosing regimen similar to that used in the clinic. The aims were to determine whether gabapentin, dosed in a manner similar to that used in the clinic, affected the various components of central sensitization and to assess the utility of this model for characterizing novel analgesics. METHODS: Intradermal capsaicin (100 microg/20 microl) was administered in the volar forearm of 41 male human volunteers to induce pain and clinical signs of central sensitization. Gabapentin (titrated to 2,400 mg daily) or placebo was given orally for 15 days in a randomized, double-blind, parallel-group design. The capsaicin test was conducted at baseline and after gabapentin or placebo. Endpoints were the size of areas of brush-evoked allodynia (with cotton gauze) and pinprick hyperalgesia (with von Frey filament), and the intensity of ongoing brush- and pinprick-evoked pain. RESULTS: Gabapentin significantly reduced the area of brush allodynia compared with placebo (P </= 0.05) and insignificantly attenuated the area of pinprick hyperalgesia. Gabapentin had no significant effect on spontaneous and evoked pain intensity. CONCLUSION: Oral gabapentin, administered to healthy volunteers in a regimen similar to that used in treating chronic neuropathic pain, reduces measures of central sensitization evoked by intradermal capsaicin. This suggests that the pain-relieving effect in chronic neuropathic pain condition is linked to the effect of gabapentin on central sensitization. The ability of the capsaicin model to detect the efficacy of this standard treatment of neuropathic pain suggests that it may have a predictive value for detection of efficacy in human subjects.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.002 | 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".