title: Synergistic analgesic effect of propofol-alfentanil combination through detecting the inhibition of cAMP signal pathway.
abstract: OBJECTIVE
  The study aims to investigate the possible mechanism of the synergistic analgesic effect of propofol-alfentanil combination.
  
  
  METHODS
  The synergistic analgesic effects of propofol-alfentanil combination in Sprague-Dawley (SD) rats were analysed through the von Frey test. Then, we examined the activity of phospholipase C (PLC) and the intracellular levels of Ca(2+) and adenosine 3', 5'cyclic monophosphate (cAMP) in primary neuronal cells of fetal SD rats. We detected the intracellular Ca(2+) concentration by fluorescence and flow cytometry. The PLC activity of the primary neuronal cells was assayed using the EnzChek(®) Direct Phospholipase C Assay Kit. The cAMP content of the cells was assayed using the cAMP Direct Immunoassay Kit (Fluorometric).
  
  
  RESULTS
  Both propofol and alfentanil treatments depressed cAMP levels and PLC activity, but propofol-alfentanil combination decreased these parameters to a greater extent than alfentanil treatment alone. Propofol and alfentanil both inhibited Ca(2+) channel, but propofol-alfentanil combination suppressed this channel to a greater extent than alfentanil treatment alone. Fluorescent image analysis revealed that both propofol and alfentanil reduced the intracellular levels of Ca(2+) , and propofol-alfentanil combination showed weaker signals than alfentanil alone. Propofol-alfentanil combination significantly reduced intracellular Ca(2+) level, cAMP level and PLC activity.
  
  
  CONCLUSIONS
  Propofol and alfentanil exert synergistic analgesic effects through the adenylyl cyclase pathway.
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Cao
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Na
authors.initials: N
authors.lastname: Jia
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Ruili
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Aidong
authors.initials: A
authors.lastname: Wen
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D015760:Alfentanil / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D000242:Cyclic AMP / Q000037:antagonists & inhibitors*; D004338:Drug Combinations; D004357:Drug Synergism; D008297:Male; D015742:Propofol / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
chemical_list: D000701:Analgesics, Opioid; D015220:Calcium Channels; D004338:Drug Combinations; D015760:Alfentanil; D000242:Cyclic AMP; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases; D002118:Calcium; D015742:Propofol
keywords: synergistic analgesic mechanism