Details

Autor(en) / Beteiligte

• M’Dahoma, Saïd
• Gadotti, Vinicius M.
• Zhang, Fang-Xiong
• Park, Byeongyeon
• Nam, Ji Hye
• Onnis, Valentina
• Balboni, Gianfranco
• Lee, Jae Yeol
• Zamponi, Gerald W.

Titel

Effect of the T-type channel blocker KYS-05090S in mouse models of acute and neuropathic pain

Ist Teil von

• Pflügers Archiv, 2016-02, Vol.468 (2), p.193-199

Ort / Verlag

Berlin/Heidelberg: Springer Berlin Heidelberg

Erscheinungsjahr

2016

Quelle

Springer LINK 全文期刊数据库

Beschreibungen/Notizen

• T-type channels are important contributors to the initiation and the maintenance of chronic pain states. Blocking T-type channels is therefore a possible therapeutic strategy for relieving pain. Here, we report the Cav3.2 T-type channel blocking action of a previously reported small organic molecule, KYS-05090S. This compound was able to reduce transiently expressed Cav3.2 currents with low micromolar affinity and mediated a hyperpolarizing shift in half-inactivation potential. KYS-05090S was then tested in models of acute and neuropathic pain. KYS-05090S (10 μg/10 μl delivered intrathecally) significantly reduced acute pain induced by formalin in both the tonic and inflammatory phases. Its antinociceptive effect was not observed when delivered to Cav3.2 null-mice revealing a Cav3.2-dependent mechanism. KYS-05090S also reduced neuropathic pain in a model of partial sciatic nerve injury. Those results indicate that KYS-05090S mediates a potent analgesic effect in inflammatory and neuropathic pain through T-type channel modulation, suggesting that its scaffold could be explored as a new class of analgesic compounds.