title: Antinociceptive synergism of gabapentin and nortriptyline in mice with partial sciatic nerve ligation.
abstract: METHODS
  Neuropathic pain results from nerve injury, and gabapentin, an antiepileptic drug, has been approved for the treatment of several types of neuropathic pain. On the other hand, nortriptyline, an antidepressant drug, has been suggested as an alternative treatment. In partial sciatic nerve ligation (PSNL) mice, the interaction of gabapentin with nortriptyline was evaluated by the hot plate assay using isobolographic analysis.
  
  
  RESULTS
  Gabapentin (3-100 mg/kg, i.p.) or nortriptyline (1-30 mg/kg, i.p.) induced dose-dependent antinociception, with an ED50 of 11.60 ± 0.54 mg/kg for gabapentin and of 5.16 ± 0.21 mg/kg for nortriptyline. The potency of gabapentin and nortriptyline in PSNL mice at 7 and 14 days after ligation was significantly increased (p < 0.05). Coadministration of gabapentin with nortriptyline, at a 1:1 ratio of their ED50, had a synergistic effect, with an interaction index of 0.311 and 0.348 for these mice at 7 and 14 days, respectively.
  
  
  CONCLUSIONS
  The data showed a synergy in antinociception at a gabapentin-to-nortriptyline ratio of 1:1 in PSNL mice. This finding suggests that this combination could provide a therapeutic alternative that can be used for neuropathic pain management.
authors.affiliation: School of Pharmacy, Faculty of Medicine, Universidad Andrés Bello, Santiago, Chile.
authors.forename: Hugo F
authors.initials: HF
authors.lastname: Miranda
authors.forename: Viviana
authors.initials: V
authors.lastname: Noriega
authors.forename: Ramiro
authors.initials: R
authors.lastname: Zepeda
authors.forename: Pilar
authors.initials: P
authors.lastname: Zanetta
authors.forename: Josefina
authors.initials: J
authors.lastname: Prieto-Rayo
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Prieto
authors.forename: Fernando
authors.initials: F
authors.lastname: Sierralta
mesh_terms: D000588:Amines / Q000627:therapeutic use*; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D000077206:Gabapentin; D006358:Hot Temperature; D008297:Male; D051379:Mice; D009437:Neuralgia / Q000188:drug therapy*; D009661:Nortriptyline / Q000627:therapeutic use*; D059348:Peripheral Nerve Injuries / Q000188:drug therapy*; D012584:Sciatic Nerve / Q000293:injuries*; D005680:gamma-Aminobutyric Acid / Q000627:therapeutic use*
chemical_list: D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D009661:Nortriptyline