A transient receptor potential vanilloid 4 contributes to mechanical allodynia following chronic compression of dorsal root ganglion in rats

The aim of the present study was to investigate the role of transient receptor potential vanilloid 4 (TRPV4) in mediating mechanical allodynia in rodent models of chronic compression of the dorsal root ganglion (CCD). First, the levels of TRPV4 mRNA and protein expression in the dorsal root ganglion (DRG) were assessed using real-time RT-PCR and Western blotting analysis respectively at 7, 14, and 28 days post-CCD. Then, the effects of spinal administration of TRPV4 antisense oligodeoxynucleotide (ODN) and mismatch ODN on CCD-induced mechanical allodynia were evaluated. Lastly, the calcium responses to hypotonic solution and 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD) were assessed following sham surgery, CCD, spinal application of TRPV4 antisense ODN and mismatch ODN. The results showed that the levels of TRPV4 mRNA and protein expression increased significantly at 7-28 days post-CCD when compared with the sham group, with the highest level at 7 days post-CCD. TRPV4 antisense ODN, but not mismatch ODN, partly reversed the CCD-induced mechanical allodynia. Additionally, TRPV4 antisense ODN had no effect on the baseline nociceptive response. The percentage of DRG neurons responsive to hypotonic solution and 4 alpha-PDD and the fluorescence ratio of calcium response were also enhanced significantly in both the CCD group and the mismatch ODN group. These increased responses were significantly inhibited by TRPV4 antisense ODN. In conclusion, TRPV4 plays a crucial role in CCD-induced mechanical allodynia. (C) 2007 Elsevier Ireland Ltd. All rights reserved.