Acute exposure to vinblastine activates mammalian sensory neurons and generates pain that is reduced in TRPA1 knockout mice.

<p><b>A</b> Representative images of Trp-V1 expressing TG neurons challenged with vinblastine (10 uM, panel ii), (100 uM, panel iv), and vinblastine + HC-030031 (10 uM; panel vi). Base line fluorescence images shown in panels i, iii, and v. <b>B</b> Graphs represent the values for the average calcium accumulation within Trp-V1 expressing TG neurons challenged with 10 uM vinblastine (gray bar) or vinblastine + HC-030031 (black bars). Error bars = SEM. n = 23–32 neurons from 4 slides per condition. P value determined using ANOVA analysis. Control noise level indicated by gray line. <b>C</b> and <b>D</b>, Single injection of vinblastine (squares) directly into the hindpaw of wild type mice (<b>C</b>) results in increased spontaneous pain compared to vehicle (circles). Values represent average duration (in seconds) in bouts of nocifensive behavior. Error bars = SEM, n = 7 animals per group. *p<0.05 determined by Student’s T-test for each point versus vehicle control. <b>E</b> and <b>F</b>, Single injection of vinblastine (striped bars) into the hindpaw results in a significant mechanical allodynia (<b>E</b>) and thermal hyperalgesia (<b>F</b>) compared to control injections (solid bars). This effect is significantly reduced in TrpA1 knock-out mice (<i>TRPA1 KO</i>, red bars). ** p<0.01 determined by Student’s T-test comparing vinblastine versus control values. † p<0.01 determined by Student’s T-test comparing wild type versus <i>TRPA1</i> mutants. Bars represent average values. Error bars = SEM, n = 7 animals per group.