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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

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2015
Authors
Tomić, Maja
Pecikoza, Uroš
Micov, Ana
Stepanović-Petrović, Radica
Article (Published version)
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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: ES...L 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.

Source:
Anesthesia and Analgesia, 2015, 121, 6, 1632-1639
Publisher:
  • Lippincott Williams & Wilkins, Philadelphia
Funding / projects:
  • Examination of mechanisms of action, toxicity and interactions of adjuvant analgesics (RS-175045)

DOI: 10.1213/ANE.0000000000000953

ISSN: 0003-2999

PubMed: 26465930

WoS: 000365499800008

Scopus: 2-s2.0-84948717282
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15
12
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/2304
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
TY  - JOUR
AU  - Tomić, Maja
AU  - Pecikoza, Uroš
AU  - Micov, Ana
AU  - Stepanović-Petrović, Radica
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2304
AB  - 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.
PB  - Lippincott Williams & Wilkins, Philadelphia
T2  - Anesthesia and Analgesia
T1  - 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
VL  - 121
IS  - 6
SP  - 1632
EP  - 1639
DO  - 10.1213/ANE.0000000000000953
ER  - 
@article{
author = "Tomić, Maja and Pecikoza, Uroš and Micov, Ana and Stepanović-Petrović, Radica",
year = "2015",
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.",
publisher = "Lippincott Williams & Wilkins, Philadelphia",
journal = "Anesthesia and Analgesia",
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",
volume = "121",
number = "6",
pages = "1632-1639",
doi = "10.1213/ANE.0000000000000953"
}
Tomić, M., Pecikoza, U., Micov, A.,& Stepanović-Petrović, R.. (2015). 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. in Anesthesia and Analgesia
Lippincott Williams & Wilkins, Philadelphia., 121(6), 1632-1639.
https://doi.org/10.1213/ANE.0000000000000953
Tomić M, Pecikoza U, Micov A, Stepanović-Petrović R. 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. in Anesthesia and Analgesia. 2015;121(6):1632-1639.
doi:10.1213/ANE.0000000000000953 .
Tomić, Maja, Pecikoza, Uroš, Micov, Ana, Stepanović-Petrović, Radica, "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" in Anesthesia and Analgesia, 121, no. 6 (2015):1632-1639,
https://doi.org/10.1213/ANE.0000000000000953 . .

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