Effect of capsaicin on voltage-gated sodium channels with <i>kdr</i> mutation from German cockroaches (<i>Blattella germanica</i>)

Capsaicin inhibits the current flow in the voltage-gated sodium channels (VGSCs) of mammals and insects. The aim of the present study was to elucidate capsaicin toxicity in pyrethroid-susceptible and knockdown resistant (<i>kdr</i>; with reduced pyrethroid sensitivity) strains of the German cockroach (<i>Blattella germanica</i>) and its effects on VGSCs carrying the <i>kdr</i> mutation. Injection tests revealed that adult cockroaches from susceptible and <i>kdr</i> strains exhibited sluggish movement and paralysis upon abdominal capsaicin administration, consistent with its inhibitory effect on VGSC currents. The LD₅₀ values of capsaicin were 16 and 36 µg per insect for the susceptible and <i>kdr</i> strains, respectively, yielding a resistance ratio of 2.3. Two-electrode voltage clamp assays showed that the EC₅₀ values for the capsaicin-mediated inhibition of VGSC currents were 4.27 and 9.19 µM for susceptible and <i>kdr</i> mutant channels, respectively, yielding a resistance ratio of 2.2. The findings indicate that capsaicin retains inhibitory activity against insect VGSCs even in the presence of <i>kdr</i> mutations.