title: Resveratrol reverses morphine-induced neuroinflammation in morphine-tolerant rats by reversal HDAC1 expression.
abstract: OBJECTIVE
  We previously showed that subsequent intrathecal (i.t.) injection of resveratrol (30 μg) significantly reverses morphine-evoked neuroinflammation in morphine-tolerant rats. The present study examined the underlying mechanism.
  
  
  METHODS
  Male Wistar rats were implanted with two i.t. catheters, one of which was connected to a miniosmotic pump and used for morphine (15 μg/h) or saline infusion for 120 hours. To examine the effects on spinal cord expression of histone deacetylase 1 (HDAC1), the inflammatory cytokine tumor necrosis factor-α (TNF-α), and TNF receptor (TNFR) 1 and TNFR2 during tolerance induction, a tail-flick test was performed prior to infusion and after 24 hours, 48 hours, 72 hours, 96 hours, and 120 hours of infusion.
  
  
  RESULTS
  Resveratrol treatment prior to morphine challenge restored the antinociceptive effect of morphine in morphine-tolerant rats and reversed the morphine infusion-induced increase in HDAC1, TNF-α, and TNFR1 expression. Moreover, chronic morphine infusion increased TNFR1-specific expression in neuron in morphine-tolerant rat spinal cords, and this effect was almost completely inhibited by resveratrol treatment prior to morphine challenge.
  
  
  CONCLUSIONS
  Resveratrol restores the antinociceptive effect of morphine by reversing morphine infusion-induced spinal cord neuroinflammation and increase in TNFR1 expression. The reversal of the morphine-induced increase in TNFR1 expression by resveratrol is partially due to reversal of the morphine infusion-induced increase in HDAC1 expression. Resveratrol pretreatment can be used as an adjuvant in clinical pain management for patients who need long-term morphine treatment or with neuropathic pain.
authors.affiliation: College of Nursing and Health Sciences, Da-Yeh University, Changhua, Taiwan.
authors.forename: Ru-Yin
authors.initials: RY
authors.lastname: Tsai
authors.affiliation: Department of Anesthesiology, Cathay General Hospital, Taipei, Taiwan.
authors.forename: Juei-Chii
authors.initials: JC
authors.lastname: Wang
authors.affiliation: General Education Center, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan.
authors.forename: Kuang-Yi
authors.initials: KY
authors.lastname: Chou
authors.affiliation: Department of Anesthesiology, Cathay General Hospital, Taipei, Taiwan; School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan; Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan. Electronic address: w82556@gmail.com.
authors.forename: Chih-Shung
authors.initials: CS
authors.lastname: Wong
authors.affiliation: Department of Anesthesiology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan. Electronic address: cherng1018@yahoo.com.tw.
authors.forename: Chen-Hwan
authors.initials: CH
authors.lastname: Cherng
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D016207:Cytokines / Q000378:metabolism; D004361:Drug Tolerance; D056284:Histone Deacetylase 1 / Q000378:metabolism*; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage; D009437:Neuralgia / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000378:metabolism; D000077185:Resveratrol; D013116:Spinal Cord / Q000187:drug effects*; D013267:Stilbenes / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D009020:Morphine; D056284:Histone Deacetylase 1; D000077185:Resveratrol
keywords: epigenetic; intrathecal; opioid; spinal