title: Potassium channel openers exhibit cross-tolerance with morphine in two experimental models of pain.
abstract: OBJECTIVE
  The study was performed to assess the effect of potassium channel openers on morphine tolerance and vice-versa.
  
  
  METHODS
  Swiss albino mice of either gender weighing between 25-30 g were used for the study The study assesses the effect of potassium channel openers (cromakalim, diazoxide and minoxidil) on morphine tolerance and vice-versa, using formalin and tail-flick tests.
  
  
  RESULTS
  The antinociceptive effect of cromakalim and minoxidil was significantly reduced when administered to morphine-tolerant mice, in both the behavioural tests. However reduced analgesic effect of diazoxide was observed on morphine-tolerance in the formalin test but not in the tail-flick test. Tolerance was observed when morphine was administered to animals chronically treated with any of the potassium channel openers. The same effect was observed when morphine was injected into a group treated with a combination of morphine and any of the potassium channel openers.
  
  
  CONCLUSIONS
  This study, therefore, suggests that both morphine and potassium channel openers are cross-tolerant. However such interaction occurs at the level of potassium channels rather than at the level of receptors.
authors.affiliation: Department of Pharmacology, University College of Medical Sciences University College of Medical Sciences (University of Delhi) Delhi 110095, India. naresh.khanna@gmail.com
authors.forename: N
authors.initials: N
authors.lastname: Khanna
authors.forename: R S
authors.initials: RS
authors.lastname: Malhotra
authors.forename: A K
authors.initials: AK
authors.lastname: Mehta
authors.forename: G R
authors.initials: GR
authors.lastname: Garg
authors.forename: S
authors.initials: S
authors.lastname: Halder
authors.forename: K K
authors.initials: KK
authors.lastname: Sharma
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D019806:Cromakalim / Q000494:pharmacology*; D003981:Diazoxide / Q000494:pharmacology*; D004361:Drug Tolerance; D015640:Ion Channel Gating / Q000187:drug effects; D051379:Mice; D008914:Minoxidil / Q000494:pharmacology*; D023421:Models, Animal; D009020:Morphine / Q000494:pharmacology*; D010146:Pain; D015221:Potassium Channels / Q000187:drug effects*
chemical_list: D000701:Analgesics, Opioid; D015221:Potassium Channels; D019806:Cromakalim; D008914:Minoxidil; D009020:Morphine; D003981:Diazoxide