Prenatal maternal stress is associated with increased sensitivity to neuropathic pain and sex-specific changes in supraspinal mRNA expression of epigenetic- and stress-related genes in adulthood
Bibliographic record
Abstract
Exposure to prenatal maternal stress impacts adult behavioral outcomes and has been suggested as a risk factor for chronic pain. However, the neurobiological mechanisms implicated are not well-characterized. In this study, we analyzed the effect of a prenatal maternal stress on the development of neuropathic pain-related behaviours and gene expression in the frontal cortex and hippocampus in adult offspring following chronic constriction injury of the sciatic nerve in male and female CD1 mice. Nerve injury-induced mechanical hypersensitivity was amplified in both male and female prenatally-stressed offspring, suggesting that prenatal stress exacerbates pain after injury. Analysis of mRNA expression of genes related to epigenetic regulation and stress responses in the frontal cortex and hippocampus, brain structures implicated in chronic pain, showed distinct sex and region-specific patterns of dysregulation. In general, mRNA expression was most frequently altered in the male hippocampus and effects of prenatal stress were more prevalent than effects of nerve injury in both supraspinal areas. These findings demonstrate the impact of prenatal stress on behavioral sensitivity to a painful injury. Changes in the expression of epigenetic- and stress-related genes suggest a possible mechanism by which the early life stress becomes embedded in the central nervous system. Increased understanding of the interactions among early-life stress, sex, and pain may lead to the identification of novel therapeutic targets and epigenetic drugs for the treatment of chronic pain disorders.
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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 | 0.006 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.001 |
| 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".