title: (+)-Naloxone inhibits morphine-induced chemotaxis via prevention of heat shock protein 90 cleavage in microglia.
abstract: OBJECTIVE
  Microglia have a crucial role in maintaining neuronal homeostasis in the central nervous system. Immune factors released from microglia have important roles in nociceptive signal transduction. Activation of microglia seems to be a shared mechanism in pathological pain and morphine tolerance because pharmacological attenuation of microglia activation provides satisfactory management in both situations.
  
  
  METHODS
  In the present study, we investigated the effect of 1nM (+)-naloxone, which is not an opioid receptor antagonist, on morphine-induced activation of microglia EOC13.31 cells.
  
  
  RESULTS
  Our results showed that 1μM morphine enhanced microglia activation and migration, decreased α-tubulin acetylation, and induced heat shock protein 90 (HSP90) fragmentation and histone deacetylase 6 (HDAC6) expression. Morphine-induced α-tubulin deacetylation and HSP90 fragmentation were HDAC6-dependent. Pretreatment with (+)-naloxone (1nM) inhibited morphine-evoked microglia activation and chemotaxis and prevented α-tubulin deacetylation and HSP90 fragmentation by inhibiting HDAC6 expression.
  
  
  CONCLUSIONS
  Based on the findings of the present study, we suggest that (+)-naloxone inhibits morphine-induced microglia activation by regulating HDAC6-dependent α-tubulin deacetylation and HSP90 fragmentation.
authors: Department of Nursing, Da-Yeh University, Changhua, Taiwan; Department of Anesthesiology, Cathay General Hospital, Taipei, Taiwan.
authors: Ru-Yin
authors: RY
authors: Tsai
authors: Department of Medical Research, Cathay General Hospital, Taipei, Taiwan.
authors: Yu-Che
authors: YC
authors: Cheng
authors: Department of Anesthesiology, Cathay General Hospital, Taipei, Taiwan; School of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan; Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan. Electronic address: w82556@gmail.com.
authors: Chih-Shung
authors: CS
authors: Wong
mesh_terms: D000818:Animals; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000378:metabolism*; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology; D015398:Signal Transduction; D014404:Tubulin / Q000378:metabolism
chemical_list: D018841:HSP90 Heat-Shock Proteins; C107835:Hspca protein, mouse; D009292:Narcotic Antagonists; D014404:Tubulin; D009270:Naloxone; D009020:Morphine; C499033:Hdac6 protein, mouse; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases
keywords: cytoskeleton; morphine tolerance; neuroinflammation; protrusion; ruffling