Src tyrosine kinase-induced mechanical hyperalgesia is TRPV4 dependent. Intradermal injection of the specific activator of Src family tyrosine kinase, YEEIP peptide (100 ng), 30 min before measurement of nociceptive thresholds, induced a decrease in mechanical nociceptive thresholds in control rats (gray bar, 34.4 ± 1.2%; n = 10). Treatment with TRPV4 antisense (AS) markedly reduced the YEEIP-induced mechanical hyperalgesia (6.8 ± 4.3% decrease in mechanical nociceptive threshold for TRPV4 antisense- and 36.2 ± 1.3% for TRPV4 mismatch (MM)-treated rats; n = 6 for each group; p < 0.0001 unpaired Student's t test). Four days after ODN injection, the decrease in nociceptive thresholds induced by intradermal injection of YEEIP peptide was not significantly different between rats previously treated with antisense or mismatch (n = 6 for each group; p > 0.05, unpaired Student's t test). *p < 0.05.