A diminished response to formalin stimulation reveals a role for the glutamate transporters in the altered pain sensitivity of mice with experimental autoimmune encephalomyelitis (EAE)
Bibliographic record
Abstract
Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) in which neuropathic pain is now recognized as a major symptom. To date, few studies have examined the underlying mechanisms of neuropathic pain in MS. Recently we showed that in a chronic-relapsing animal model of MS, experimental autoimmune encephalomyelitis (EAE), characteristic neuropathic behaviours develop. However, responses to persistent noxious stimuli in EAE remain unexplored. We, therefore set out to characterize the changes in pain sensitivity in our EAE model to subcutaneous injection of formalin. We show here that female C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein (MOG(35-55)) display a significant decrease in elicited pain behaviours in response to formalin injection. These effects were found to involve dysregulation of the glutamatergic system in EAE. We show here that these effects are mediated by decreased glutamate transporter expression associated with EAE. Our findings demonstrate that dysregulation of glutamate transporter function in EAE mice is an important mechanism underlying the abnormal pain sensitivity in response to persistent noxious stimulation of mice with EAE and also sheds light on a potential mechanism underlying neuropathic pain behaviours in this model.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.017 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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) | 0.000 | 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 teacher head, 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".