Angiotensin II type 1 receptor activation induces dorsal horn capillary constriction and pain hypersensitivity
Bibliographic record
Abstract
Vascular disturbance is a key factor in the development of neurological disease, with reduced integrity of the capillary network in the dorsal horn implicated in activation of nociceptive neural circuits and induction of pain states. Pericytes regulate capillary health and tone, with pericyte dysfunction in cerebral tissue associated with neurodegenerative disorders. Our work demonstrates that spinal cord nociceptive processing is influenced by angiotensin II type 1 (AT1) receptor mediated capillary constriction. Intravital imaging of the mouse spinal cord demonstrated angiotensin II induced cessation of spinal cord capillary perfusion. Intrathecal administration of angiotensin II induced narrowing of capillary diameter, which was accompanied by mechanical allodynia and heat hyperalgesia in adult male and female mice. Angiotensin II mediated reduction of spinal cord blood flow and pericyte activation, was prevented by AT1 receptor inhibition via losartan treatment. Losartan prevented angiotensin II induced pain. Integrity of dorsal horn capillary endothelium was protected by co-treatment with losartan preventing angiotensin II induced loss of CD31 immunoreactivity. This investigation demonstrates that AT1 regulates the dorsal horn capillary network and is fundamental in modulating nociceptive processing and perception of pain. Here we identify a novel cellular and mechanistic target for the induction of pain hypersensitivity. PERSPECTIVE: Intrathecally delivered Angiotensin II induced mechanical and heat hypersensitivity in male and female mice. Capillary constriction in the dorsal horn was induced by Angiotensin II treatment and led to degeneration of the endothelium. Angiotensin II induced pericyte activation was Angiotensin II type 1 receptor dependent.
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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) | 0.000 | 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 | 0.001 |
| 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".