title: Nifedipine potentiates the antinociceptive effect of endomorphin-1 microinjected into the periaqueductal gray in rats.
abstract: Endomorphin-1 is a novel endogenous mu-opioid ligand. We investigated the antinociceptive interaction between endomorphin-1 and nifedipine, an L-type calcium channel blocker, microinjected into the midbrain ventrolateral periaqueductal gray (vPAG), using the spinally-organized tail-flick test and the supraspinally-organized tail-pressure test in rats. Sprague-Dawley rats were stereotaxically implanted with a guide cannula lowered into the vPAG. Microinjection of endomorphin-1 into the vPAG led to dose-related increases in antinociceptive responses in the tail-flick test and tail-pressure test. Pretreatment with the mu-opioid receptor-selective antagonist beta-funaltrexamine blocked the antinociceptive effect of endomorphin-1. Pretreatment with beta-funaltrexamine alone had no effect on the tail-flick latency and tail-pressure threshold. Microinjection of nifedipine alone into the vPAG did not produce an antinociceptive response in the tail-flick test and tail-pressure test. However, injection of nifedipine into the vPAG potentiated the antinociceptive effect of endomorphin-1, producing a significant leftward shift in the dose-response curve of endomorphin-1 in both the tail-flick and tail-pressure tests. This result shows that the potent antinociceptive effect of endomorphin-1 microinjected into the vPAG is mediated through the mu-opioid receptor and is potentiated by concomitant administration of nifedipine.
  
  
  CONCLUSIONS
  This study shows that the potent antinociceptive effect of endomorphin-1 microinjected into the ventrolateral periaqueductal gray is potentiated by concomitant administration of nifedipine. This suggests that calcium channel blockers may enhance the analgesia of opioids in patients with calcium channel blocker treatment.
authors.affiliation: *Department of Anesthesiology & Critical Care Medicine, Asahikawa Medical College, Asahikawa, Japan; and †Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Micheal J
authors.initials: MJ
authors.lastname: Cousins
authors.forename: Shuanglin
authors.initials: S
authors.lastname: Hao
authors.forename: Keiko
authors.initials: K
authors.lastname: Mamiya
authors.forename: Osamu
authors.initials: O
authors.lastname: Takahata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwasaki
authors.forename: Marina
authors.initials: M
authors.lastname: Mata
authors.forename: David J
authors.initials: DJ
authors.lastname: Fink
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D019540:Area Under Curve; D001522:Behavior, Animal / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008845:Microinjections; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology*; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D010487:Periaqueductal Gray; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D002121:Calcium Channel Blockers; D009292:Narcotic Antagonists; D009842:Oligopeptides; C105293:endomorphin 1; D009271:Naltrexone; C024524:beta-funaltrexamine; D009543:Nifedipine