title: Hyperbaric oxygen treatment at various stages following chronic constriction injury produces different antinociceptive effects via regulation of P2X4R expression and apoptosis.
abstract: OBJECTIVE
  The aims of this study were to investigate the effect of hyperbaric oxygen (HBO) treatment at various stages following chronic constriction injury (CCI) and to explore the underlying mechanisms of HBO treatment.
  
  
  METHODS
  Forty adult male Sprague-Dawley rats were randomly assigned to five groups (n = 8 for each group): the sham group, CCI group, HBO1 group, HBO2 group, and HBO3 group. Neuropathic pain was induced by CCI of the sciatic nerve. HBO treatment began on postoperative days 1, 6, and 11 and continued for 5 days. The mechanical withdrawal threshold and thermal withdrawal latency were tested on preoperative day 3 and postoperative days 1, 3, 5, 7, 10, 14, and 21. The expression of P2X4R was determined by immunohistochemistry and western blot analysis. Cell apoptosis was measured using TUNEL staining. The expression of caspase 3 was measured using reverse transcription polymerase chain reaction (RT-PCR). Electron microscopy was used to determine the ultrastructural changes.
  
  
  RESULTS
  Early HBO treatment beginning on postoperative day 1 produced a persistent antinociceptive effect and inhibited the CCI-induced increase in the expression of P2X4R without changing CCI-induced apoptosis. In contrast, late HBO treatment beginning on postoperative day 11 produced a persistent antinociceptive effect and inhibited CCI-induced apoptosis and upregulation of caspase-3 without changing the expression of P2X4R. In addition, late HBO treatment reduced CCI-induced ultrastructural damage. However, HBO treatment beginning on postoperative day 6 produced a transient antinociceptive effect without changing the expression of P2X4R or CCI-induced apoptosis.
  
  
  CONCLUSIONS
  HBO treatment at various stages following CCI can produce antinociceptive effects via different mechanisms. Early HBO treatment is associated with inhibition of P2X4R expression, and late HBO treatment is associated with inhibition of cell apoptosis.
authors: Department of Anesthesiology, Guangzhou Women and Children's Medical Center, 510623, Guangzhou, China.
authors: Bai-Song
authors: BS
authors: Zhao
authors: Department of Anesthesiology, Guangzhou Women and Children's Medical Center, 510623, Guangzhou, China.
authors: Xing-Rong
authors: XR
authors: Song
authors: Department of Anesthesiology, Guangzhou Women and Children's Medical Center, 510623, Guangzhou, China.
authors: Pei-Ying
authors: PY
authors: Hu
authors: Department of Pain, The Shengjing Hospital of China Medical University, 110004, Shenyang, China.
authors: Ling-Xin
authors: LX
authors: Meng
authors: Department of Anesthesiology, Guangzhou Women and Children's Medical Center, 510623, Guangzhou, China.
authors: Yong-Hong
authors: YH
authors: Tan
authors: Department of Anesthesiology, Guangzhou Women and Children's Medical Center, 510623, Guangzhou, China.
authors: Ying-Jun
authors: YJ
authors: She
authors: Department of Pain, The Shengjing Hospital of China Medical University, 110004, Shenyang, China.
authors: Yuan-Yuan
authors: YY
authors: Ding
mesh_terms: D000700:Analgesics / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal; D002251:Carbon Tetrachloride / Q000633:toxicity; D053148:Caspase 3 / Q000378:metabolism; D003250:Constriction; D004195:Disease Models, Animal; D006931:Hyperbaric Oxygenation; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D009437:Neuralgia / Q000139:chemically induced / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D058848:Receptors, Purinergic P2X4 / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000700:Analgesics; D058848:Receptors, Purinergic P2X4; D002251:Carbon Tetrachloride; D053148:Caspase 3