Eslicarbazepine acetate reduces trigeminal nociception: Possible role of adrenergic, cholinergic and opioid receptors
Abstract
Aims: Eslicarbazepine acetate (ESL) is a novel dibenzazepine antiepileptic, that has demonstrated efficacy against trigeminal pain, both in preclinical and clinical studies. However, ESL's mechanism of antinociceptive action remains uncertain. Here, we aimed to examine the contribution of adrenergic/cholinergic/opioid receptors to the antinociceptive effects of ESL in a trigeminal pain model, as these neurotransmitter systems are known to have an important role in the modulation of trigeminal nociception. Main methods: ESL's effects in the orofacial formalin test were examined following peroral and local peripheral administration (subcutaneous, into the perinasal region). The involvement of adrenergic/cholinergic/opioid receptors was evaluated by intraperitoneally pretreating mice with an appropriate antagonist immediately after peroral application of ESL. We used antagonists of alpha(1)-adrenergic (prazosin), alpha(2)-adrenergic (yohimbine), beta(3)-adrenergic (non-selective, proprano...lol and beta(1)-selective, metoprolol), muscarinic (atropine), nicotinic (mecamylamine) and opioid receptors (naloxone). Additionally, the role of peripheral alpha(2)-adrenergic, beta(1)-adrenergic, muscarinic and opioid receptors was evaluated by co-injecting ESL with an antagonist into the perinasal area. Key findings: ESL dose-dependently reduced formalin-induced nociceptive behavior after systemic and local peripheral application. Systemic administration of yohimbine, propranolol, metoprolol, atropine and naloxone inhibited ESL's antinociceptive effects in a dose-related manner. Prazosin and mecamylamine did not produce inhibitory effects. Local application of yohimbine, atropine and naloxone into the perinasal area also produced a dose-related inhibition of ESL's efficacy, whereas metoprolol failed to inhibit the local antinociceptive effects of ESL. Significance: This study suggests that ESL's efficacy against trigeminal nociception is mediated by peripheral (and possibly central) alpha(2)-adrenergic, muscarinic and opioid receptors, as well as central beta(1)-adrenergic receptors.
Keywords:
Eslicarbazepine acetate / Trigeminal pain / Orofacial formalin test / Adrenergic receptors / Cholinergic receptors / Opioid receptorsSource:
Life Sciences, 2018, 214, 167-175Publisher:
- Pergamon-Elsevier Science Ltd, Oxford
Funding / projects:
DOI: 10.1016/j.lfs.2018.10.059
ISSN: 0024-3205
PubMed: 30393024
WoS: 000450360000019
Scopus: 2-s2.0-85055971551
Collections
Institution/Community
PharmacyTY - JOUR AU - Pecikoza, Uroš AU - Micov, Ana AU - Tomić, Maja AU - Stepanović-Petrović, Radica PY - 2018 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3061 AB - Aims: Eslicarbazepine acetate (ESL) is a novel dibenzazepine antiepileptic, that has demonstrated efficacy against trigeminal pain, both in preclinical and clinical studies. However, ESL's mechanism of antinociceptive action remains uncertain. Here, we aimed to examine the contribution of adrenergic/cholinergic/opioid receptors to the antinociceptive effects of ESL in a trigeminal pain model, as these neurotransmitter systems are known to have an important role in the modulation of trigeminal nociception. Main methods: ESL's effects in the orofacial formalin test were examined following peroral and local peripheral administration (subcutaneous, into the perinasal region). The involvement of adrenergic/cholinergic/opioid receptors was evaluated by intraperitoneally pretreating mice with an appropriate antagonist immediately after peroral application of ESL. We used antagonists of alpha(1)-adrenergic (prazosin), alpha(2)-adrenergic (yohimbine), beta(3)-adrenergic (non-selective, propranolol and beta(1)-selective, metoprolol), muscarinic (atropine), nicotinic (mecamylamine) and opioid receptors (naloxone). Additionally, the role of peripheral alpha(2)-adrenergic, beta(1)-adrenergic, muscarinic and opioid receptors was evaluated by co-injecting ESL with an antagonist into the perinasal area. Key findings: ESL dose-dependently reduced formalin-induced nociceptive behavior after systemic and local peripheral application. Systemic administration of yohimbine, propranolol, metoprolol, atropine and naloxone inhibited ESL's antinociceptive effects in a dose-related manner. Prazosin and mecamylamine did not produce inhibitory effects. Local application of yohimbine, atropine and naloxone into the perinasal area also produced a dose-related inhibition of ESL's efficacy, whereas metoprolol failed to inhibit the local antinociceptive effects of ESL. Significance: This study suggests that ESL's efficacy against trigeminal nociception is mediated by peripheral (and possibly central) alpha(2)-adrenergic, muscarinic and opioid receptors, as well as central beta(1)-adrenergic receptors. PB - Pergamon-Elsevier Science Ltd, Oxford T2 - Life Sciences T1 - Eslicarbazepine acetate reduces trigeminal nociception: Possible role of adrenergic, cholinergic and opioid receptors VL - 214 SP - 167 EP - 175 DO - 10.1016/j.lfs.2018.10.059 ER -
@article{ author = "Pecikoza, Uroš and Micov, Ana and Tomić, Maja and Stepanović-Petrović, Radica", year = "2018", abstract = "Aims: Eslicarbazepine acetate (ESL) is a novel dibenzazepine antiepileptic, that has demonstrated efficacy against trigeminal pain, both in preclinical and clinical studies. However, ESL's mechanism of antinociceptive action remains uncertain. Here, we aimed to examine the contribution of adrenergic/cholinergic/opioid receptors to the antinociceptive effects of ESL in a trigeminal pain model, as these neurotransmitter systems are known to have an important role in the modulation of trigeminal nociception. Main methods: ESL's effects in the orofacial formalin test were examined following peroral and local peripheral administration (subcutaneous, into the perinasal region). The involvement of adrenergic/cholinergic/opioid receptors was evaluated by intraperitoneally pretreating mice with an appropriate antagonist immediately after peroral application of ESL. We used antagonists of alpha(1)-adrenergic (prazosin), alpha(2)-adrenergic (yohimbine), beta(3)-adrenergic (non-selective, propranolol and beta(1)-selective, metoprolol), muscarinic (atropine), nicotinic (mecamylamine) and opioid receptors (naloxone). Additionally, the role of peripheral alpha(2)-adrenergic, beta(1)-adrenergic, muscarinic and opioid receptors was evaluated by co-injecting ESL with an antagonist into the perinasal area. Key findings: ESL dose-dependently reduced formalin-induced nociceptive behavior after systemic and local peripheral application. Systemic administration of yohimbine, propranolol, metoprolol, atropine and naloxone inhibited ESL's antinociceptive effects in a dose-related manner. Prazosin and mecamylamine did not produce inhibitory effects. Local application of yohimbine, atropine and naloxone into the perinasal area also produced a dose-related inhibition of ESL's efficacy, whereas metoprolol failed to inhibit the local antinociceptive effects of ESL. Significance: This study suggests that ESL's efficacy against trigeminal nociception is mediated by peripheral (and possibly central) alpha(2)-adrenergic, muscarinic and opioid receptors, as well as central beta(1)-adrenergic receptors.", publisher = "Pergamon-Elsevier Science Ltd, Oxford", journal = "Life Sciences", title = "Eslicarbazepine acetate reduces trigeminal nociception: Possible role of adrenergic, cholinergic and opioid receptors", volume = "214", pages = "167-175", doi = "10.1016/j.lfs.2018.10.059" }
Pecikoza, U., Micov, A., Tomić, M.,& Stepanović-Petrović, R.. (2018). Eslicarbazepine acetate reduces trigeminal nociception: Possible role of adrenergic, cholinergic and opioid receptors. in Life Sciences Pergamon-Elsevier Science Ltd, Oxford., 214, 167-175. https://doi.org/10.1016/j.lfs.2018.10.059
Pecikoza U, Micov A, Tomić M, Stepanović-Petrović R. Eslicarbazepine acetate reduces trigeminal nociception: Possible role of adrenergic, cholinergic and opioid receptors. in Life Sciences. 2018;214:167-175. doi:10.1016/j.lfs.2018.10.059 .
Pecikoza, Uroš, Micov, Ana, Tomić, Maja, Stepanović-Petrović, Radica, "Eslicarbazepine acetate reduces trigeminal nociception: Possible role of adrenergic, cholinergic and opioid receptors" in Life Sciences, 214 (2018):167-175, https://doi.org/10.1016/j.lfs.2018.10.059 . .