title: Analgesic effects of antidepressants alone and after their local co-administration with morphine in a rat model of neuropathic pain.
abstract: BACKGROUND
  The therapy of neuropathic pain may include the use of co-analgesics, such as antidepressants, however, their desired analgesic effect is associated with significant side effects. An alternative approach to this is their local administration which has been proposed, but there is little data regarding their local co-administration with morphine and the nature of the interaction between morphine and either doxepin or venlafaxine, two antidepressant drugs that have been recently used in neuropathic pain therapies.
  
  
  METHODS
  This study was performed on rats after chronic constriction injury (CCI) to the sciatic nerve. The von Frey and Hargreaves' tests were used to assess mechanical allodynia and thermal hyperalgesia, respectively, after intraplantar (ipl) or subcutaneous (sc) administration of amitriptyline, doxepin, or venlafaxine, or their ipl co-administration with morphine on day 12-16 after injury.
  
  
  RESULTS
  The ipl administration of amitriptyline (3, 15 mg), doxepin (1, 5, 10, 15 mg), or venlafaxine (2, 7 mg) was effective in antagonizing CCI-induced allodynia. Their sc injection at a site distal to the injured side, did not induce alterations in pain thresholds, which supports the local mode of action. Of the three antidepressants used in this study, only ipl co-administration of amitriptyline with morphine significantly enhanced its effect in contrast to doxepin and venlafaxine, both of which weakened the analgesic effect of morphine.
  
  
  CONCLUSIONS
  In summary, the results suggest that when amitriptyline (but not doxepin or venlafaxine) is locally co-administered with morphine the effectiveness under neuropathic pain is enhanced, although additional studies are necessary to explain differential mechanisms of interaction of antidepressant drugs with morphine after local administration.
authors.affiliation: Department of Pain Treatment and Palliative Care, University Hospital, Kraków, Poland; Department of Anatomy, Medical College Jagiellonian University, Kraków, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Jagla
authors.affiliation: Department of Pain Pharmacology, Institute of Pharmacology, Kraków, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Mika
authors.affiliation: Department of Pain Pharmacology, Institute of Pharmacology, Kraków, Poland.
authors.forename: Wioletta
authors.initials: W
authors.lastname: Makuch
authors.affiliation: Department of Pain Pharmacology, Institute of Pharmacology, Kraków, Poland.
authors.forename: Ilona
authors.initials: I
authors.lastname: Obara
authors.affiliation: Department of Pain Treatment and Palliative Care, University Hospital, Kraków, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Wordliczek
authors.affiliation: Department of Pain Pharmacology, Institute of Pharmacology, Kraków, Poland. Electronic address: przebar@if-pan.krakow.pl.
authors.forename: Barbara
authors.initials: B
authors.lastname: Przewlocka
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003511:Cyclohexanols / Q000494:pharmacology; D004195:Disease Models, Animal; D004316:Doxepin / Q000494:pharmacology; D006930:Hyperalgesia; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009437:Neuralgia / Q000188:drug therapy*; D010147:Pain Measurement / Q000295:instrumentation; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D012584:Sciatic Nerve / Q000187:drug effects; D000069470:Venlafaxine Hydrochloride
chemical_list: D000700:Analgesics; D000928:Antidepressive Agents; D003511:Cyclohexanols; D004316:Doxepin; D000639:Amitriptyline; D009020:Morphine; D000069470:Venlafaxine Hydrochloride
keywords: Amitriptyline; Doxepin; Morphine; Neuropathic pain; Venlafaxine