title: Enhancement of antinociceptive effect of morphine by antidepressants in diabetic neuropathic pain model.
abstract: BACKGROUND
  Recent studies have shown that influence of antidepressants on analgesic action of opioids is heterogeneous. The aim of this study was to investigate the effect of acute and repeated (21 days) antidepressant (amitriptyline, moclobemide and reboxetine) treatment on the antinociceptive action of morphine, an opioid agonist, in streptozotocin (STZ)-induced neuropathic pain model.
  
  
  METHODS
  The studies were performed on the male Wistar rats. The changes in nociceptive thresholds were determined by using mechanical stimuli (the Randall-Selitto and the von Frey tests). Diabetes was induced by intramuscular administration of STZ.
  
  
  RESULTS
  In this work we report that acute as well as repeated per os administration of antidepressants (amitriptyline, moclobemide and reboxetine) significantly potentiated the antihyperalgesic effect of morphine in STZ-induced neuropathic pain model.
  
  
  CONCLUSIONS
  Combination therapy, such as classical antidepressants (amitriptyline, moclobemide) with opioids, or agents with noradrenaline reuptake inhibition and μ-opioid receptor activation could be a new target for research into treatment of painful diabetic neuropathy.
authors.affiliation: Department of Pharmacodynamics, Medical University of Warsaw, Warsaw, Poland. Electronic address: kcegielska@wum.edu.pl.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Cegielska-Perun
authors.affiliation: Department of Pharmacodynamics, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bujalska-Zadrożny
authors.affiliation: Department of Pharmacodynamics, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Emilia
authors.initials: E
authors.lastname: Gąsińska
authors.affiliation: Department of Pharmacodynamics, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Helena Elżbieta
authors.initials: HE
authors.lastname: Makulska-Nowak
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D004195:Disease Models, Animal; D004357:Drug Synergism; D008297:Male; D009020:Morphine / Q000627:therapeutic use*; D009437:Neuralgia / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin
chemical_list: D000701:Analgesics, Opioid; D000928:Antidepressive Agents; D013311:Streptozocin; D009020:Morphine
keywords: Amitriptyline; Diabetes; Morphine; Pain; Streptozotocin-induced hyperalgesia