Effect of local administration of eicosapentaenoic acid on the jaw-opening reflex in rats

Although eicosapentaenoic acid (EPA) application in vitro inhibits voltage-gated Na⁺ (Nav) channels in excitable tissues, the acute local effect of EPA on the jaw-opening reflex in vivo remains unknown. The aim of the present study was to determine whether local administration of EPA to adult male Wistar rats could attenuate the excitability of the jaw-opening reflex in vivo, including nociception. The jaw-opening reflex evoked by electrical stimulation of the tongue was recorded by a digastric muscle electromyogram (dEMG) in pentobarbital-anesthetized rats. The amplitude of the dEMG response was significantly increased in proportion to the electrical stimulation intensity (1×–5× threshold). At 3×, local administration of EPA dose-dependently inhibited the dEMG response, lasting 60 min, with maximum inhibition observed within approximately 10 min. The mean magnitude of dEMG signal inhibition by EPA was almost equal to that observed with a local anesthetic, 1% lidocaine, and with a half dose of lidocaine plus a half dose of EPA. These findings suggest that EPA attenuates the jaw-opening reflex, possibly by blocking Nav channels of primary nerve terminals, and strongly support the idea that EPA is a potential therapeutic agent and complementary alternative medicine for the prevention of acute trigeminal nociception.     

Thrombocytopenia during avacopan administration: A case report

Avacopan is a novel C5a receptor antagonist recently approved for the treatment of microscopic polyangiitis and granulomatosis with polyangiitis. To our knowledge, thrombocytopenia induced by avacopan has not been reported. We report a case of a 78-year-old man with microscopic polyangiitis who developed rapidly progressive glomerulonephritis (RPGN) and vasculitis neuropathy. After developing RPGN, he was treated with prednisolone, which was ineffective. As the dosage of corticosteroids was decreased, he developed impaired dorsiflexion of the left ankle, tingling and numbness in his feet, consistent with vasculitis neuropathy. After a 3-day administration of methylprednisolone, we started avacopan and prednisolone 20 mg/d to reduce the corticosteroid dosage. One week after starting avacopan, platelet counts began to decrease, eventually leading to the cessation of the drug. The possibility of thrombotic microangiopathy and heparin-induced thrombocytopenia was considered unlikely given the clinical course and laboratory studies. After 3 weeks of avacopan cessation, platelet counts began to increase, suggesting avacopan as the most probable cause of thrombocytopenia. Our case highlights the importance of postmarketing surveillance of avacopan to identify its adverse events that were not reported in clinical trials to ensure its safe use. Clinicians should carefully monitor platelet counts when using avacopan.