title: Role of melatonin in the prevention of morphine-induced hyperalgesia and spinal glial activation in rats: protein kinase C pathway involved.
abstract: OBJECTIVE
  Morphine can induce tolerance and hyperalgesia after long-term administration. Glial activation is believed to cause and maintain a state of morphine-induced pain hypersensitivity. The present study examines the effect of melatonin on tolerance, hyperalgesia, and reactive gliosis induced by morphine in rats.
  
  
  METHODS
  The study examines the effect of melatonin on morphine-induced hyperalgesia using tail-flick test. Immunohistochemistry and Western blot was performed to investigate the expression of glial fibrillary acidic protein (GFAP) indicative of spinal glial activity. This study also measures protein kinase C (PKC) activity and cyclic adenosine monophosphate (cAMP) levels in spinal cords to investigate the mechanisms which melatonin involved.
  
  
  RESULTS
  When coadministered intragastrically (i.g.) with morphine, melatonin in doses of 50 or 100 mg/kg significantly prevented hyperalgesia after termination of morphine. Immunohistochemistry and Western blot with GFAP revealed that melatonin significantly decreased morphine-induced over-expression of GFAP in spinal cord (p < .05). By measuring PKC activity and cAMP levels, the upregulated PKC activity and cAMP levels induced by morphine were significantly inhibited by melatonin.
  
  
  CONCLUSIONS
  Melatonin can prevent morphine-withdrawal-induced hyperalgesia and glial reactivity. This effect of melatonin after morphine administration may mediated by inhibiting PKC activity and cAMP upregulation.
authors: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Antiinflammatory and Immunopharmacology, Ministry of Education, Hefei, P. R. China.
authors: Wei
authors: W
authors: Xin
authors: Wang
authors: W
authors: Chun
authors: Lin
authors: L
authors: Ling
authors: Wei
authors: W
authors: Wei
mesh_terms: D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D008550:Melatonin / Q000494:pharmacology* / Q000627:therapeutic use; D009021:Morphine Dependence / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement / Q000379:methods; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000700:Analgesics; D011493:Protein Kinase C; D008550:Melatonin