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.
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ジャーナル |
Eur J Neurosci
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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.
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巻・号 |
25(10)
|
ページ |
2956-63
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公開日 |
2007-5-1
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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 |
|