Reduction of beta-endorphin-containing immune cells in inflamed paw tissue corresponds with a reduction in immune-derived antinociception: reversible by donor activated lymphocytes.
The functional integrity of the immune system is essential for peripheral antinociception. Previous studies have demonstrated that immune cells elicit potent antinociception in inflamed tissues and that corticotropin-releasing factor-induced antinociception is significantly inhibited in animals that have undergone cyclosporin A (CsA)-induced immunosuppression. In this study, we examined the effect of a single bolus of CsA on inflammatory nociception. CsA-treated rats had substantially increased nociception compared with nonimmunosuppressed rats, consistent with a reduction in circulating and infiltrating lymphocytes. Furthermore, CsA-treated rats had inhibition of corticotropin-releasing factor-induced immune-derived antinociception, which was dose-dependently reversed by IV injection of concanavalin A-activated donor lymphocytes (1.0-7.0 x 10(6) cells/0.1 mL). In conclusion, our findings provided further evidence that opioid-containing immune cells are essential for peripheral analgesia. It is evident from these findings that control of inflammatory pain relies heavily on a functioning immune system.


CONCLUSIONS
The immune system not only contributes to inflammation, but also provides localized analgesia. A depleted immune system results in a reduction of immune-derived analgesia and a potentiation of inflammatory pain. Donor activated lymphocytes reverse these effects, highlighting the importance of a functional immune system in inflammatory pain.
The School of Pharmacy, The University of Queensland, Queensland, Australia.
Siobhan
S
Hermanussen
MyHong
M
Do
Peter John
PJ
Cabot
D000698:Analgesia; D000818:Animals; D018791:CD4 Lymphocyte Count; D003208:Concanavalin A; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D005528:Foot / Q000473:pathology; D005620:Freund's Adjuvant; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000502:physiology*; D008214:Lymphocytes / Q000276:immunology* / Q000502:physiology*; D008297:Male; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D001615:beta-Endorphin / Q000378:metabolism*
D007166:Immunosuppressive Agents; D003208:Concanavalin A; D001615:beta-Endorphin; D016572:Cyclosporine; D005620:Freund's Adjuvant