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A-type potassium channel mechanism-based diclofenac therapy for bone cancer pain

A-type potassium channel mechanism-based diclofenac therapy ...

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中国生理学会第23届全国会员代表大会暨生理学学术大会

作者： Kai-Zheng DUAN,Qian XU,Zhi-Qi ZHAO,Yu-Qiu ZHANG~* Institute of Neurobiology,Institutes of Brain Science and State Key Laboratory of Medical Neurobiology,Fudan University, Shanghai 200032,China

Bone cancer pain significantly affects quality of life and survival of patients with *** mechanism-based therapies to treat this unique cancer-related pain is becoming *** we reported that A-type shaker family potassium channels involved the peripheral neuropathy of bone cancer pain in rats,and the possible mechanism of diclofenac,a non-steroidal anti-inflammatory agent(NSAID),therapy for this distinct chronic ***-cell recording results showed that there was a functional change of A-type potassium channels on small dorsal root ganglia(drg) neurons during bone caner ***+ neurons mainly expressed the typical A-type potassium currents,which were increased at cancer 14 day,and then declined at cancer 21 *** and western blot analysis revealed mat bone cancer caused a profound reduction in Kv1.4 subunit at cancer 21 day,especially the Kv1.4 that is associated with A-type potassium currents in small drg *** reduction in Kv1.4 was prevented by consecutively administrating with ***,diclofenac not only attenuated tumor burden,but also had a good analgesic effect for bone cancer pain by enhancing A-type potassium currents *** results extend the basic understanding on cancer pain and provide a new mechanism-based therapy for bone cancer pain.

关键词： bone cancer pain A-type Kv channels diclofenac small drg neurons

来源： cnki会议评论

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Changes in A-type voltage-gated K+ currents and capsaicin-activated currents on the small sensory neurons of dorsal root ganglion following the development of rat bone cancer pain

Changes in A-type voltage-gated K+ currents and capsaicin-ac...

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中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Kai-Zheng DUAN,Qian XU,Zhi-Qi ZHAO,Yu-Qiu ZHANG~* Institute of Neurobiology,Institutes of Brain Science,and State Key Laboratory of Medical Neurobiology,Fudan University,Shanghai,200032,China

Objective Although bone cancer pain is one of the most severe and common chronic pain conditions,the basic neurobiology of bone cancer pain is poorly *** Rat model of bone cancer pain was built by an injection of Walker256 mammary gland carcinoma cells into the tibia medullary *** cell patch-clamp recording was carried out to investigate the functional changes of A-type voltage-gated K(Kv) channels and TRPV1 channel,which may play a fundamental role in determining the neural excitability,on acutely dissociated small neurons of dorsal root ganglion (drg) from native or bone cancer pain *** A-type Kv currents were mainly expressed on the IB4-positive neurons,and the current densities were changed *** activating kinetics of the rapid inactivating A-type Kv channels was right shifted following bone cancer *** addition,as a natural character of TRPV1 channel,capsaicinactivated currents exhibits a tendency to be ***,at 21 days after inoculation carcinoma cells,the capsaicin-induced currents were less desensitized with 0.5μM capsaicin repeated treatment compared with native group, indicating that TRPV1 channel was sensitized in later phase of rat bone cancer *** findings may help us understanding the mechanisms underlying bone cancer pain,providing a potential strategy for therapies and improving the quality of life of cancer patients.

关键词： bone cancer pain A-type Kv channels TRPV1 small drg neurons

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