The neural cell adhesion molecule antibody blocks cold water swim stress-induced analgesia and cell adhesion between lymphocytes and cultured dorsal root ganglion neurons.
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 beta-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 microM beta-endorphin, which was reversed by 100 microM 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.
Hua
Susan
S
The School of Pharmacy, The University of Queensland, 4072, Queensland, Australia.
Hermanussen
Siobhan
S
Tang
Linda
L
Monteith
Greg R
GR
Cabot
Peter J
PJ
D000698:Analgesia; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002448:Cell Adhesion; D002478:Cells, Cultured; D005283:Fentanyl / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D008214:Lymphocytes / Q000473:pathology*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D019006:Neural Cell Adhesion Molecules / Q000276:immunology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000503:physiopathology*; D013550:Swimming; D001615:beta-Endorphin / Q000032:analysis
D000911:Antibodies, Monoclonal; D019006:Neural Cell Adhesion Molecules; D018799:Intercellular Adhesion Molecule-1; D009270:Naloxone; D001615:beta-Endorphin; D005283:Fentanyl