Nuclear factor-kappa B mediates TRPV4-NO pathway involved in thermal hyperalgesia following chronic compression of the dorsal root ganglion in rats

The aim of this study was to test the hypothesis that nuclear factor-kappa B (NF-kappa B) is involved in TRPV4-NO pathway in thermal hyperalgesia following chronic compression of the dorsal root ganglion (DRG) (the procedure hereafter termed CCD) in rat. Intrathecal administration of two NF-kappa B inhibitors, dithiocarbamate (PDTC; 10(-1) to 10(-2) M) and BAY (100-50 mu M), both induced significantly dose-dependent increase in the paw withdrawal latency (PWL) and decrease in nitric oxide (NO) content in DRG when compared with control rats. Pretreatment with 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD, transient receptor potential vanilloid 4 (TRPV4) synthetic activator, 1 nm) attenuated the suppressive effects of PDTC (10(-1) M) and BAY (100 mu M) on CCD-induced thermal hyperalgesia and NO production. In addition, Western blot analysis indicated that CCD rats exhibited nuclear NF-kappa B protein expression and low levels of cytoplasmic inhibitory-kappa B (I-kappa B) expression; the increase in NF-kappa B expression and decrease in I-kappa B expression were reversed after intrathecal injection of PDTC. In conclusion, our data suggested that NF-kappa B could be involved in TRPV4-NO pathway in CCD-induced thermal hyperalgesia. (C) 2011 Elsevier B.V. All rights reserved.