Evidence of photophobia and lateralized head pain in the transgenic «Cacna1a» mouse model of migraine
Bibliographic record
Abstract
Migraine is a highly prevalent, disabling and complex episodic brain disorder not known to occur in animals. The pathogenesis is poorly understood, largely due to the lack of validated animal models. Here we report behavioural evidence of hallmark migraine features, unilateral headache and photophobia, in a transgenic knock-in mouse bearing the human familial hemiplegic migraine, type 1 (FHM-1) R192Q gain-of-function mutation of the Cacna1a gene encoding the Cav2.1 calcium channel α1 subunit. Photophobia was demonstrated using a modified elevated plus maze test in which the safe closed arms were brightly illuminated; mutant mice avoided the light despite showing no differences in the standard anxiety version of the test. Multiple behavioural measures of head pain were found. These behaviours were: (a) more frequent in mutant versus wildtype mice; (b) lateralized in mutant but not in wildtype mice; (c) more frequent in females versus males; and (d) dose dependently normalized in mutant mice by systemic administration of two different acute antimigraine agents, rizatriptan and morphine. There were no consistent genotype differences in sensitivity to thermal, mechanical and chemical/inflammatory pain applied outside the head area, indicating that mutants had otherwise normal pain processing. Using Fos protein as a marker of neuronal activation, we found no differences in activity levels within the trigeminal nucleus caudalis (TNC) of mutants and wildtypes. However, we did obtain a significant negative correlation between Fos levels and blink rate among mutants, suggesting that this behaviour may be a marker of abnormal nociceptive activity within the TNC. Finally, we found unexpected and striking coat colour differences in head grooming and eye behaviours that strongly suggest the presence of a modifier gene interacting with Cacna1a to increase the expression of migraine-relevant behaviours in 192Q mutants. We thus believe
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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 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".