title: Inhibition of sensory neuronal TRPs contributes to anti-nociception by butamben.
abstract: Butamben (n-butyl-p-aminobenzoic acid) is a pain-relieving local anesthetic for topical use. Blockade of voltage-gated channel expressed in the peripheral sensory neurons has been suggested as a mechanism of action. Its effects on another sensory neuronal channel family, transient receptor potential (TRP) have remained unclear. In this study we attempted to address this question using six sensory neuronal TRP channel-expressing heterologous systems, cultured sensory neurons and TRP-mediated acute animal pain tests. In Ca(2+) imaging and whole cell electrophysiology, TRPA1 and TRPV4 were blocked by micromolar butamben. Butamben also activated TRPA1 at millimolar concentrations. The inhibitory effects on the two TRP channels were reproducible in sensory neurons. Moreover, butamben attenuated acute animal pain behaviors in a TRPA1- or TRPV4-dependent manner. Para-aminobenzoic acid (PABA), an analog of a simpler chemical structure, displayed similar in vitro and in vivo properties, suggestive that chemical structure is important for the two TRP-specificity. Our findings suggest that inhibition of TRPA1 and TRPV4 contribute to the peripheral analgesic mechanisms of butamben.
authors: Korea University Graduate School of Medicine, Seoul 136-705, Republic of Korea.
authors: Sangsu
authors: S
authors: Bang
authors: Tae-Jin
authors: TJ
authors: Yang
authors: Sungjae
authors: S
authors: Yoo
authors: Tae-Hwe
authors: TH
authors: Heo
authors: Sun Wook
authors: SW
authors: Hwang
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001566:Benzocaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D010146:Pain / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D050052:TRPC Cation Channels / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D000779:Anesthetics, Local; D050052:TRPC Cation Channels; D050916:TRPV Cation Channels; C486576:Trpv4 protein, mouse; C096351:transient receptor potential cation channel, subfamily C, member 1; C004605:butamben; D001566:Benzocaine