title: Nuclear factor-kappa B mediates TRPV4-NO pathway involved in thermal hyperalgesia following chronic compression of the dorsal root ganglion in rats.
abstract: The aim of this study was to test the hypothesis that nuclear factor-kappa B (NF-κB) 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-κB inhibitors, pyrrolidine dithiocarbamate (PDTC; 10(-1) to 10(-2)M) and BAY (100-50 μM), 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 4α-phorbol 12,13-didecanoate (4α-PDD, transient receptor potential vanilloid 4 (TRPV4) synthetic activator, 1 nm) attenuated the suppressive effects of PDTC (10(-1)M) and BAY (100 μM) on CCD-induced thermal hyperalgesia and NO production. In addition, Western blot analysis indicated that CCD rats exhibited nuclear NF-κB protein expression and low levels of cytoplasmic inhibitory-kappa B (I-κB) expression; the increase in NF-κB expression and decrease in I-κB expression were reversed after intrathecal injection of PDTC. In conclusion, our data suggested that NF-κB could be involved in TRPV4-NO pathway in CCD-induced thermal hyperalgesia.
authors.affiliation: Department of Physical Medicine & Rehabilitation, Qilu Hospital, Medical School of Shandong University, Jinan 250012, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Ning
authors.forename: Yong-Hui
authors.initials: YH
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xin-Li
authors.initials: XL
authors.lastname: Ding
authors.forename: Hong-You
authors.initials: HY
authors.lastname: Ge
authors.forename: Lars
authors.initials: L
authors.lastname: Arendt-Nielsen
authors.forename: Shou-Wei
authors.initials: SW
authors.lastname: Yue
mesh_terms: D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology*; D020672:I-kappa B Proteins / Q000096:biosynthesis / Q000502:physiology; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D009408:Nerve Compression Syndromes / Q000150:complications; D009437:Neuralgia / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology / Q000627:therapeutic use; D010704:Phorbols / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013450:Sulfones / Q000494:pharmacology / Q000627:therapeutic use; D050916:TRPV Cation Channels / Q000819:agonists*; D013859:Thiocarbamates / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; C517592:4alpha-phorbol 12,13-didecanone; D000700:Analgesics; D020672:I-kappa B Proteins; D016328:NF-kappa B; D009570:Nitriles; D010704:Phorbols; D011759:Pyrrolidines; D013450:Sulfones; D050916:TRPV Cation Channels; D013859:Thiocarbamates; C486577:Trpv4 protein, rat; C020972:pyrrolidine dithiocarbamic acid; D009569:Nitric Oxide