title: Ultra-low dose naloxone restores the antinocicepitve effect of morphine in PTX-treated rats: association of IL-10 upregulation in the spinal cord.
abstract: OBJECTIVE
  Ultra-low dose naloxone has been shown to restore the antinociceptive effect of morphine in pertussis toxin (PTX)-treated rats by suppressing spinal microglia activation and inhibiting inflammatory cytokine expression. This study was further investigated the mechanism by which ultra-low dose naloxone promotes analgesia in pertussis toxin-treated rats.
  
  
  METHODS
  Male Wistar rats were implanted with an intrathecal (i.t.) catheter and injected either saline or PTX (1 μg). Four days later, rats randomly received either saline, or ultra-low dose naloxone, or recombinant rat interleukin-10 (rrIL-10) (1 μg) injection followed by saline or morphine (10 μg) 30 min later. In some experiments, mouse anti-rat IL-10 antibody (10 μg) was injected intrathecally into PTX injected rats daily on days 4, 5, 6, and 7. On day 7, ultra-low dose naloxone was given 1h after antibody injection with or without subsequent morphine injection.
  
  
  RESULTS
  PTX injection induced notable thermal hyperalgesia and mechanical allodynia. Injection of ultra-low dose naloxone preserved the antinociceptive effect of morphine in PTX-treated rats and associated an increasing of IL-10 protein expression. Intrathecal injection rrIL-10 alone or in combination with morphine, not only reversed mechanical allodynia but also partially restored the antinociceptive effect of morphine; injection of anti-rat IL-10 antibody attenuated the effect of morphine plus ultra-low dose naloxone on mechanical allodynia and completely inhibited the antinociceptive effect of morphine.
  
  
  CONCLUSIONS
  These results indicate that intrathecal ultra-low dose naloxone induces IL-10 expression in spinal neuron and microglia, which suppresses PTX-induced neuroinflammation and restores the antinociceptive effect of morphine.
authors: Neuropathic Pain and Translational Medicine Research Laboratory, Cathay Medical Research Institute, Cathay General Hospital, Xizhi, New Taipei City, Taiwan.
authors: Yaoh-Shiang
authors: YS
authors: Lin
authors: Ru-Yin
authors: RY
authors: Tsai
authors: Ching-Hui
authors: CH
authors: Shen
authors: Chih-Cheng
authors: CC
authors: Chien
authors: Wei-Yuan
authors: WY
authors: Tsai
authors: Shu-Lin
authors: SL
authors: Guo
authors: Chih-Shung
authors: CS
authors: Wong
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D016753:Interleukin-10 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D017628:Microglia / Q000378:metabolism; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D037342:Pertussis Toxin / Q000633:toxicity; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D000906:Antibodies; D009292:Narcotic Antagonists; D011994:Recombinant Proteins; D016753:Interleukin-10; D009270:Naloxone; D009020:Morphine; D037342:Pertussis Toxin