Peripheral gabapentin regulates mosquito allergy-induced itch in mice

The antipruritic activity of gabapentin, an anticonvulsant, was studied in a mouse model of allergic itch. In mice sensitized by an extract of the salivary glands of the mosquito (ESGM), an intradermal injection of ESGM elicited scratching and increased peripheral nerve firing. Oral or intradermal administration of gabapentin at the ESGM injection site inhibited ESGM-induced scratching and peripheral nerve firing. However, gabapentin did not affect histamine-induced scratching. The distributions of immunoreactivity to the voltage-dependent calcium channel alpha(2)delta-1 subunit, a site of gabapentin action, and the histamine H-1 receptor differed in the mouse dorsal root ganglia. The alpha(2)delta-1 subunit was mainly found in neurons that were 15-20 mu m in diameter, whereas the H-1 receptor was mainly in 20-30 mu m neurons. In addition, alpha(2)delta-1 subunit immunoreactivity co-localized with that of transient receptor potential vanilloid 1 (TRPV1). These results suggest that gabapentin regulates allergic itch by acting on the calcium channel alpha(2)delta-1 subunit in peripheral TRPV1-positive neurons.