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: 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.
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Authors | Maja A Tomić, Uroš B Pecikoza, Ana M Micov, Radica M Stepanović-Petrović |
Journal | Anesthesia and analgesia
(Anesth Analg)
Vol. 121
Issue 6
Pg. 1632-9
(Dec 2015)
ISSN: 1526-7598 [Electronic] United States |
PMID | 26465930
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Dibenzazepines
- Receptor, Cannabinoid, CB1
- Receptor, Cannabinoid, CB2
- Receptor, Serotonin, 5-HT1B
- Receptor, Serotonin, 5-HT1D
- eslicarbazepine acetate
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Topics |
- Animals
- Diabetic Neuropathies
(drug therapy, pathology)
- Dibenzazepines
(pharmacology, therapeutic use)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Male
- Mice
- Mice, Inbred C57BL
- Pain Measurement
(drug effects, methods)
- Receptor, Cannabinoid, CB1
(physiology)
- Receptor, Cannabinoid, CB2
(physiology)
- Receptor, Serotonin, 5-HT1B
(physiology)
- Receptor, Serotonin, 5-HT1D
(physiology)
- Treatment Outcome
- Trigeminal Nerve Diseases
(drug therapy, pathology)
- Visceral Pain
(drug therapy, pathology)
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