title: Involvement of TRPV4-NO-cGMP-PKG pathways in the development of thermal hyperalgesia following chronic compression of the dorsal root ganglion in rats.
abstract: The aim of the present study was to test the hypothesis that the TRPV4-NO-cGMP-PKG cascade is involved in the maintenance of thermal hyperalgesia following chronic compression of the dorsal root ganglion (DRG) (the procedure hereafter termed CCD) in rats. CCD rats showed thermal hyperalgesia and increased nitrite production. Intrathecal administration of ruthenium red (TRPV4 antagonist, 0.1-1 nmol), TRPV4 antisense ODN (TRPV4 AS, 40 microg, daily for 7 days), N(G)-L-nitro-arginine methyl ester (l-NAME, inhibitor of NO synthase, 30-300 nmol), 1H-[1,2,4]-oxadiazolo [4,3-a] quinoxalin-1-one (ODQ, a soluble guanylate cyclase inhibitor, 50-100 nmol) or 8-(4-Chlorophenylthio) guanosine 3',5'-cyclic Monophosphothioate, Rp-Isomer sodium salt (Rp-8-pCPT-cGMPS, a PKG inhibitor, 25-50 nmol) induced a significant (P<0.001) and dose-dependent increase in the paw withdrawal latency (PWL) compared with control rats, respectively. Ruthenium red (1 nmol), TRPV4 AS (40 microg, daily for 7 days) or L-NAME (300 nmol) decreased nitrite (an index of nitric oxide formation) in the DRG of CCD rats. In addition, the phorbol ester 4alpha-phorbol 12,13-didecanoate (4alpha-PDD, TRPV4 synthetic activator, 1 nmol), co-administered with L-NAME (300 nmol), attenuated the suppressive effect of L-NAME on CCD-induced thermal hyperalgesia and nitrite production. Our data suggested that the TRPV4-NO-cGMP-PKG pathway could be involved in CCD-induced thermal hyperalgesia.
authors: Department of Physical Medicine & Rehabilitation, Qilu Hospital, Medical School of Shandong University, Jinan 250012, China.
authors: Xin-Li
authors: XL
authors: Ding
authors: Yong-Hui
authors: YH
authors: Wang
authors: Li-Ping
authors: LP
authors: Ning
authors: Yang
authors: Y
authors: Zhang
authors: Hong-You
authors: HY
authors: Ge
authors: Hong
authors: H
authors: Jiang
authors: Rong
authors: R
authors: Wang
authors: Shou-Wei
authors: SW
authors: Yue
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D017288:Pain Threshold / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D011843:Radiculopathy / Q000150:complications / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D012428:Ruthenium / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D018709:Statistics, Nonparametric; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D009573:Nitrites; D020319:Oligodeoxyribonucleotides, Antisense; D050916:TRPV Cation Channels; C486577:Trpv4 protein, rat; D009569:Nitric Oxide; D012428:Ruthenium; D011493:Protein Kinase C; D006152:Cyclic GMP