The Neural Cell Adhesion Molecule Antibody Blocks Cold Water Swim Stress-Induced Analgesia and Cell Adhesion Between Lymphocytes and Cultured Dorsal Root Ganglion Neurons
Bibliographic record
Abstract
In Brief BACKGROUND: Opioid-containing immune cells migrate in a site-directed manner into inflamed tissue and adhere to sensory nerve fibers. These cells release opioid peptides in close proximity to these fibers, thereby avoiding localized degradation by peptidases, and delivering opioid peptides proximal to opioid receptors to provide antinociception. METHODS: The effects of the anti–neural-cell-adhesion molecule (anti-NCAM) were assessed on cold water swim stress-induced antinociception in Wistar rats with Freund’s adjuvant-induced inflammation of one hindpaw. Algesiometry was assessed for both thermal and mechanical stimuli. Cell adhesion experiments examining the effects of β-endorphin and antibodies to NCAM and intercellular cell adhesion molecule-1 and were performed on cultured dorsal root ganglion neurons and isolated lymphocytes. Lymphocyte binding was determined by fluorescence using calcein AM loaded into freshly isolated lymphocytes. RESULTS: The direct adhesion between lymphocytes and cultured sensory neurons was inhibited by anti-NCAM. This adhesion was also demonstrated to be opioid dependent, with lymphocyte adhesion to cultured sensory neurons reduced in the presence of 1 μM β-endorphin, which was reversed by 100 μM naloxone. Moreover, anti-NCAM blocked cold-water-swim-induced analgesia in inflamed paws both to thermal and mechanical stimuli. However, anti-NCAM did not affect fentanyl-induced antinociception. CONCLUSIONS: This study provides insight into the role of cell adhesion molecules in lymphocyte adhesion to sensory neurons and a link to immune-derived antinociception. IMPLICATIONS: The immune system not only contributes to inflammation, it also provides localized analgesia. The means by which this analgesia is provided within inflamed tissue is not fully understood. These studies demonstrate evidence for the direct adhesion between neurons and immune cells in vitro and the role this adhesion may have in immune-derived analgesia. This has implications on new therapeutics that might enhance this binding interaction to improve analgesic effects.
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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 | 0.000 | 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 | 0.001 | 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".