Life sciences · 2018
Eslicarbazepine acetate reduces trigeminal nociception: Possible role of adrenergic, cholinergic and opioid receptors.
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Pecikoza Uroš, Micov Ana, Tomić Maja, Stepanović-Petrović Radica
Аннотация
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 α1‑adrenergic (prazosin), α2‑adrenergic (yohimbine), β‑adrenergic (non-selective, propranolol and β1-selective, metoprolol), muscarinic (atropine), nicotinic (mecamylamine) and opioid receptors (naloxone). Additionally, the role of peripheral α2‑adrenergic, β1‑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) α2‑adrenergic, muscarinic and opioid receptors, as well as central β1‑adrenergic receptors.
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 α1‑adrenergic (prazosin), α2‑adrenergic (yohimbine), β‑adrenergic (non-selective, propranolol and β1-selective, metoprolol), muscarinic (atropine), nicotinic (mecamylamine) and opioid receptors (naloxone). Additionally, the role of peripheral α2‑adrenergic, β1‑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) α2‑adrenergic, muscarinic and opioid receptors, as well as central β1‑adrenergic receptors.