Stimulation of sensory neuropeptide release by nociceptin/orphanin FQ leads to hyperaemia in acutely inflamed rat knees
Bibliographic record
Abstract
The peripheral effect of the 'opioid-like' peptide nociceptin/orphanin FQ (N/OFQ) on joint blood flow was investigated in acutely inflamed rats. Sensory neuropeptide release from capsaicin-sensitive nerves and the involvement of synovial mast cells and leukocytes on these vasomotor responses were also studied. Blood flow measurements of exposed knee joints were performed in urethane-anaesthetised rats (2 mg kg(-1) intraperitoneal) using laser Doppler perfusion imaging. Topical administration of N/OFQ (10(-13)-10(-8) mol) to acutely inflamed joints caused a dose-dependent increase in synovial perfusion with an ED(50) of 4.0 x 10(-10) mol. This vasodilatatory response was blocked by the selective NOP receptor antagonist [Phe(1)-(CH(2)-NH)-Gly(2)]-Nociceptin(1-13)-NH(2) (10(-9) mol) (P<0.0001).Co-administration of N/OFQ with the neurokinin-1 (NK(1)) receptor antagonist [D-Arg1,D-Phe5,D-Trp7,9,Leu11]-Substance P (10(-12) mol), the vasoactive intestinal peptide (VIP) receptor antagonist VIP(6-28) (10(-9) mol) or the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP(8-37) (10(-9) mol) all blocked the hyperaemic effect of N/OFQ (P<0.0001). Treatment of acutely inflamed knees with capsaicin (8-methyl-N-vanillyl-6-noneamide) to destroy unmyelinated joint afferents also inhibited N/OFQ vasomotor activity. Stabilisation of synovial mast cells with disodium cromoglycate (cromolyn) ameliorated N/OFQ responses, whereas inactivation of circulating leukocytes with the pan-selectin inhibitor fucoidin completely blocked N/OFQ-induced hyperaemia in these joints. These experiments show that in acutely inflamed knee joints, N/OFQ acts on NOP receptors located on synovial mast cells and leukocytes leading to the secondary release of proinflammatory mediators into the joint. These agents subsequently stimulate sensory neuropeptide release from capsaicin-sensitive nerves culminating in vasodilatation and increased articular blood flow.
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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 | 0.001 |
| 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".