title: Isobolographic analysis in mice of the interaction of gabapentin and nortriptyline in relieving orofacial pain.
abstract: OBJECTIVE
  To evaluate the nature of the antinociceptive interaction of systemic administration of a combination of the anticonvulsant gabapentin with the antidepressant nortriptyline, by isobolographic analysis in the formalin orofacial pain test of mice.
  
  
  METHODS
  The study was carried out in 168 male CF-1 mice weighing 30 g, and the protocol was to test each drug (at dosages of 1, 3, 10, 30, and 100 mg/kg of gabapentin and 0.1, 1, 3, 10, and 30 mg/kg of nortriptyline; ip) alone and in combination. The isobolographic assay has two phases: phase 1 corresponds to the 5-minute period starting immediately after the formalin injection and reflects a tonic acute pain due to peripheral nociceptor sensitization; phase 2 is recorded as the 10-minute period starting 20 minutes after the formalin injection and reflects an inflammatory pain state. Results were analyzed by Student t test for independent means.
  
  
  RESULTS
  Gabapentin was 1.61 times more potent in phase 2 than in phase 1, and nortriptyline 1.37 times more potent in phase 2 than in phase 1. The combination of both drugs was synergic, with an index of interaction of 0.134 and 0.148 for phase 1 and phase 2, respectively. Differences in the pharmacological profiles of gabapentin and nortriptyline could underlie the synergism of the two drugs.
  
  
  CONCLUSIONS
  The findings of this study are important, because they are concordant with some clinical studies and also raise the possibility of potential clinical advantages of combining gabapentin and nortriptyline in pain management, since the low doses of the components may potentially have a lower incidence of adverse reactions.
authors.forename: Hugo F
authors.initials: HF
authors.lastname: Miranda
authors.forename: Viviana
authors.initials: V
authors.lastname: Noriega
authors.forename: Pilar
authors.initials: P
authors.lastname: Zanetta
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Prieto
mesh_terms: D000588:Amines / Q000627:therapeutic use*; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use*; D004357:Drug Synergism; D005157:Facial Pain / Q000188:drug therapy*; D000077206:Gabapentin; D016014:Linear Models; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009661:Nortriptyline / Q000627:therapeutic use*; D005680:gamma-Aminobutyric Acid / Q000627:therapeutic use*
chemical_list: D000588:Amines; D000927:Anticonvulsants; D000928:Antidepressive Agents; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D009661:Nortriptyline