RRC ID 42981
著者 Kasama S, Kawakubo M, Suzuki T, Nishizawa T, Ishida A, Nakayama J.
タイトル RNA interference-mediated knock-down of transient receptor potential vanilloid 1 prevents forepaw inflammatory hyperalgesia in rat.
ジャーナル Eur J Neurosci
Abstract Transient receptor potential vanilloid (TRPV)1 is a ligand-gated cation channel expressed by primary sensory neurons, including those in the dorsal root ganglia (DRG). TRPV1 plays an essential role in development of inflammatory thermal hyperalgesia after tissue injury and its expression in rat lumbar DRG is increased after hindpaw inflammation. However, the identity of factors mediating forepaw inflammatory hyperalgesia has remained elusive. Here, we examined behavioral responses to noxious thermal stimuli after forepaw inflammation in rats and found that inflammation induced by intraplantar injection of complete Freund's adjuvant significantly reduced hot-plate latency (HPL) at 50 degrees C. TRPV1 expression levels in the ipsilateral cervical DRG were also elevated after forepaw inflammation. By contrast, HPL at 56 degrees C was not shortened after forepaw inflammation and expression of TRPV2, a TRPV1 homolog, in the DRG was not increased. Paratracheal injection of short interfering RNA targeting TRPV1 blocked TRPV1 up-regulation in cervical DRG and abolished inflammation-mediated HPL reductions seen at 50 degrees C. However, thermal hyperalgesia previously established by inflammation was not reversed by short interfering RNA injection. These results indicate that: (i) enhanced TRPV1 expression in cervical DRG is closely associated with development of inflammatory thermal hyperalgesia in the forepaw after tissue injury and (ii) RNA interference targeting TRPV1 prevents inflammatory thermal hyperalgesia after forepaw injuries but does not ameliorate it when already established in a rat model of nociceptive pain representing upper limb injury in humans.
巻・号 25(10)
ページ 2956-63
公開日 2007-5-1
DOI 10.1111/j.1460-9568.2007.05584.x
PII EJN5584
PMID 17509082
MeSH Animals Disease Models, Animal Down-Regulation / genetics Forelimb / innervation Forelimb / physiopathology Freund's Adjuvant / adverse effects Ganglia, Spinal / metabolism Ganglia, Spinal / physiopathology Hyperalgesia / genetics* Hyperalgesia / metabolism Hyperalgesia / physiopathology Inflammation / genetics* Inflammation / metabolism Inflammation / physiopathology Inflammation Mediators / adverse effects Male Neurons, Afferent / metabolism* Nociceptors / metabolism Nociceptors / physiopathology* PC12 Cells Pain Threshold / physiology RNA Interference* RNA, Small Interfering / pharmacology Rats Rats, Sprague-Dawley Reaction Time / genetics Sensory Receptor Cells / metabolism Sensory Receptor Cells / physiopathology Skin / innervation Skin / physiopathology TRPV Cation Channels / genetics*
IF 3.115
引用数 29
WOS 分野 NEUROSCIENCES
リソース情報
ヒト・動物細胞