title: The Efficacy of Eslicarbazepine Acetate in Models of Trigeminal, Neuropathic, and Visceral Pain: The Involvement of 5-HT1B/1D Serotonergic and CB1/CB2 Cannabinoid Receptors.
abstract: BACKGROUND
  Many clinical pain states that are difficult to treat share a common feature of sensitization of nociceptive pathways. Drugs that could normalize hyperexcitable neural activity (e.g., antiepileptic drugs) may be useful in relieving these pain states. Eslicarbazepine acetate (ESL) is a novel antiepileptic drug derived from carbamazepine/oxcarbazepine with a more favorable metabolic profile and potentially better tolerability. We examined the efficacy of ESL in models of inflammatory and neuropathic pain and the potential mechanism involved in its action.
  
  
  METHODS
  The antinociceptive effects of ESL were assessed in mice models of trigeminal (orofacial formalin test), neuropathic (streptozotocin-induced diabetic neuropathy model), and visceral pain (writhing test). The influence of 5-HT1B/1D serotonin receptor (GR 127935) and CB1 (AM251) and CB2 cannabinoid receptor (AM630) antagonists on the antinociceptive effect of ESL was tested in the model of trigeminal pain.
  
  
  RESULTS
  ESL exhibited significant and dose-dependent antinociceptive effects in the second phase of the orofacial formalin test (P ≤ 0.011), in the tail-flick test in diabetic mice (P ≤ 0.013), and in the writhing test (P ≤ 0.003). GR 127935 (P ≤ 0.038) and AM251 and AM630 (P ≤ 0.013 for both antagonists) significantly inhibited the antinociceptive effect of ESL in a dose-related manner.
  
  
  CONCLUSIONS
  ESL exhibited efficacy in models of trigeminal, neuropathic, and visceral pain. In the trigeminal pain model, the antinociceptive effect of ESL is, at least in part, mediated by 5-HT1B/1D serotonin and CB1/CB2 cannabinoid receptors. This study indicates that ESL could be useful in the clinical treatment of inflammatory and neuropathic pain.
authors.affiliation: From the Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
authors.forename: Maja A
authors.initials: MA
authors.lastname: Tomić
authors.forename: Uroš B
authors.initials: UB
authors.lastname: Pecikoza
authors.forename: Ana M
authors.initials: AM
authors.lastname: Micov
authors.forename: Radica M
authors.initials: RM
authors.lastname: Stepanović-Petrović
mesh_terms: D000818:Animals; D003929:Diabetic Neuropathies / Q000188:drug therapy / Q000473:pathology; D003984:Dibenzazepines / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D043884:Receptor, Cannabinoid, CB1 / Q000502:physiology*; D043885:Receptor, Cannabinoid, CB2 / Q000502:physiology*; D044302:Receptor, Serotonin, 5-HT1B / Q000502:physiology*; D044346:Receptor, Serotonin, 5-HT1D / Q000502:physiology*; D016896:Treatment Outcome; D020433:Trigeminal Nerve Diseases / Q000188:drug therapy* / Q000473:pathology; D059265:Visceral Pain / Q000188:drug therapy / Q000473:pathology
chemical_list: D003984:Dibenzazepines; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; C416835:eslicarbazepine acetate