論文

査読有り
2013年9月

Spinal NTS2 receptor activation reverses signs of neuropathic pain

FASEB JOURNAL
  • Pascal Tetreault
  • Nicolas Beaudet
  • Amelie Perron
  • Karine Belleville
  • Adeline Rene
  • Florine Cavelier
  • Jean Martinez
  • Thomas Stroh
  • Ashley M. Jacobi
  • Scott D. Rose
  • Mark A. Behlke
  • Philippe Sarret
  • 全て表示

27
9
開始ページ
3741
終了ページ
3752
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1096/fj.12-225540
出版者・発行元
FEDERATION AMER SOC EXP BIOL

Management of painful peripheral neuropathies remains challenging, since patients with chronic pain respond poorly to the available pharmacopeia. In recent years, the G-protein-coupled receptor neurotensin (NT) type 2 (NTS2) emerged as an attractive target for treating transitory pain states. To date, however, there is no evidence for its role in the regulation of chronic peripheral neuropathies. Here, we found that NTS2 receptors were largely localized to primary afferent fibers and superficial dorsal horns. Changes in the time course of the gene expression profile of NT, NTS1, and NTS2 were observed over a 28-d period following the sciatic nerve constriction [chronic constriction injury (CCI) model]. We next determined the effects of central delivery of selective-NTS2 agonists to CCI-treated rats on both mechanical allodynia (evoked withdrawal responses) and weight-bearing deficits (discomfort and quality-of-life proxies). The NTS2 analogs JMV431, levocabastine, and -lactotensin were all effective in reducing ongoing tactile allodynia in CCI-treated rats. Likewise, amitriptyline, pregabalin, and morphine significantly attenuated CCI-induced mechanical hypersensitivity. NTS2 agonists were also efficient in reversing weight-bearing and postural deficits caused by nerve damage, unlike reference analgesics currently used in the clinic. Thus, NTS2 agonists may offer new treatment avenues for limiting pain associated with peripheral neuropathies and improve functional rehabilitation and well-being.Tetreault, P., Beaudet, N., Perron, A., Belleville, K., Rene, A., Cavelier, F., Martinez, J., Stroh, T., Jacobi, A. M., Rose, S. D., Behlke, M. A., Sarret, P. Spinal NTS2 receptor activation reverses signs of neuropathic pain.

リンク情報
DOI
https://doi.org/10.1096/fj.12-225540
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/23756650
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000328840500032&DestApp=WOS_CPL
ID情報
  • DOI : 10.1096/fj.12-225540
  • ISSN : 0892-6638
  • eISSN : 1530-6860
  • PubMed ID : 23756650
  • Web of Science ID : WOS:000328840500032

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