title: Spatio-temporal expression and functional involvement of transient receptor potential vanilloid 1 in diabetic mechanical allodynia in rats.
abstract: Diabetic neuropathic pain (DNP) is one of the most common clinical manifestations of diabetes mellitus (DM), which is characterized by prominent mechanical allodynia (DMA). However, the molecular mechanism underlying it has not fully been elucidated. In this study, we examined the spatio-temporal expression of a major nociceptive channel protein transient receptor potential vanilloid 1 (TRPV1) and analyzed its functional involvement by intrathecal (i.t.) application of TRPV1 antagonists in streptozocin (STZ)-induced DMA rat models. Western blot and immunofluorescent staining results showed that TRPV1 protein level was significantly increased in the soma of the dorsal root ganglion (DRG) neurons on 14 days after STZ treatment (DMA 14 d), whereas those in spinal cord and skin (mainly from the central and peripheral processes of DRG neurons) had already been enhanced on DMA 7 d to peak on DMA 14 d. qRT-PCR experiments confirmed that TRPV1 mRNA level was significantly up-regulated in the DRG on DMA 7 d, indicating a preceding translation of TRPV1 protein in the soma but preferential distribution of this protein to the processes under the DMA conditions. Cell counting assay based on double immunostaining suggested that increased TRPV1-immunoreactive neurons were likely to be small-sized and CGRP-ergic. Finally, single or multiple intrathecal applications of non-specific or specific TRPV1 antagonists, ruthenium red and capsazepine, at varying doses, effectively alleviated DMA, although the effect of the former was more prominent and long-lasting. These results collectively indicate that TRPV1 expression dynamically changes during the development of DMA and this protein may play important roles in mechanical nociception in DRG neurons, presumably through facilitating the release of CGRP.
authors.affiliation: Department of Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, Preclinical School of Medicine, Fourth Military Medical University, Xi'an, China; Institution of Basic Medical Science and Lab of Cell Biology & Translational Medicine, Xi'an Medical University, Xi'an, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Cui
authors.affiliation: Department of Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, Preclinical School of Medicine, Fourth Military Medical University, Xi'an, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology, Fuzhou General Hospital Affiliated to Fujian Medical University, Fuzhou, China.
authors.forename: Huang-Hui
authors.initials: HH
authors.lastname: Wu
authors.affiliation: Department of Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, Preclinical School of Medicine, Fourth Military Medical University, Xi'an, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, Preclinical School of Medicine, Fourth Military Medical University, Xi'an, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, Preclinical School of Medicine, Fourth Military Medical University, Xi'an, China.
authors.forename: Yun-Qing
authors.initials: YQ
authors.lastname: Li
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002211:Capsaicin / Q000031:analogs & derivatives; D003929:Diabetic Neuropathies / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005727:Ganglia, Spinal / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D006930:Hyperalgesia / Q000209:etiology* / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D012430:Ruthenium Red; D013116:Spinal Cord / Q000378:metabolism; D013311:Streptozocin; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors
chemical_list: D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D012430:Ruthenium Red; D013311:Streptozocin; C071423:capsazepine; D002211:Capsaicin