title: The antinociceptive effect of dexmedetomidine modulates spleen cell immunity in mice.
abstract: BACKGROUND
  Pain plays roles in both the nervous system and immune system. Changes in the neuroendocrine pathway under pain conditions give rise to sympathetic outflow with increased plasma catecholamines and activate immune reactions. Dexmedetomidine exerts sedative, analgesic, and anesthetic-sparing effects and is known to diminish pro-inflammatory processes by central sympatholytic effects. To investigate the influence of the analgesic effect of dexmedetomidine on immunomodulation under pain conditions, splenic natural killer (NK) tumoricidal cytotoxic activity, proliferative ability of T lymphocytes, and cytokine changes were assessed.
  
  
  METHODS
  After evaluation of the analgesic efficacy of dexmedetomidine in C57BL mice that were subjected to formalin-induced pain, dexmedetomidine (30 µg/kg) or saline was injected intraperitoneally (ip) 30 min before formalin (20 µL of 2% formalin in 0.9% saline) injection. NK cell activity against NK-sensitive YAC-1 lymphoma cells was evaluated by the percentage of specific lactate dehydrogenase (LDH) release. Various numbers of effector cells (NK cells) were added to the wells of a microtiter plate containing 2 × 10(4) target YAC-1 cells in 100 μL, to achieve final effector-to-target cell ratios of 80:1, 40:1, and 20:1. The level of lymphocyte proliferation in response to phytohemagglutinin (PHA) was detected by bromodeoxyuridine (BrdU) incorporation assay. TNF-α, IL-1β, and IL-10 levels were determined in blood samples and supernatants of splenocyte preparations.
  
  
  RESULTS
  IP administration of dexmedetomidine significantly decreased the time of licking and biting during the first and second phases of the formalin test (p <0.001). Formalin-induced pain led to higher activity of NK cells than in sham-treated mice (p <0.05), but NK activity was not increased significantly by ip dexmedetomidine treatment. Formalin-induced pain significantly increased splenic lymphocyte proliferation (p <0.05), but dexmedetomidine did not alter this response. There was a significant increase in plasma TNF-α (p = 0.048) and IL-6 (p = 0.014) levels after formalin-induced pain. However, the differences between the responses after ip dexmedetomidine did not change significantly.
  
  
  CONCLUSIONS
  Dexmedetomidine showed antinociceptive effect on both of acute pain phase 1 and hyperalgesic phase 2 of formalin pain model. Formalin-induced pain alters cellular immunity of spleen in mice. Dexmedetomidine attenuates the activation of NK cells under pain condition, but neither the proliferative response of the splenic lymphocytes nor the cytokine production was affected by dexmedetomidine.
authors: 1. Department of Anesthesiology and pain medicine, The Catholic University of Korea, Inchon St. Mary's Hospital, 56 Dongsu-ro, Bupyong-gu, Incheon, S.Korea 403-720.
authors: Yeon
authors: Y
authors: Jang
authors: 2. Clinical Research Laboratory, The Catholic University of Korea, Inchon St. Mary's Hospital, 56 Dongsu-ro, Bupyong-gu, Incheon, S.Korea 403-720.
authors: Mi-Young
authors: MY
authors: Yeom
authors: 2. Clinical Research Laboratory, The Catholic University of Korea, Inchon St. Mary's Hospital, 56 Dongsu-ro, Bupyong-gu, Incheon, S.Korea 403-720.
authors: Eun-Sun
authors: ES
authors: Kang
authors: 1. Department of Anesthesiology and pain medicine, The Catholic University of Korea, Inchon St. Mary's Hospital, 56 Dongsu-ro, Bupyong-gu, Incheon, S.Korea 403-720.
authors: Ji-Won
authors: JW
authors: Kang
authors: 1. Department of Anesthesiology and pain medicine, The Catholic University of Korea, Inchon St. Mary's Hospital, 56 Dongsu-ro, Bupyong-gu, Incheon, S.Korea 403-720.
authors: Ho-Kyung
authors: HK
authors: Song
mesh_terms: D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D020927:Dexmedetomidine / Q000008:administration & dosage*; D005557:Formaldehyde / Q000633:toxicity; D007109:Immunity / Q000187:drug effects*; D016753:Interleukin-10 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000187:drug effects
chemical_list: D000700:Analgesics; D016753:Interleukin-10; D005557:Formaldehyde; D020927:Dexmedetomidine
keywords: Antinociceptive Effect; Cell Immunity; Dexmedetomidine; Mice