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Targeting A-type K(+) Channels in Primary Sensory Neurons for Bone Cancer Pain in a Rat Model

Targeting A-type K(+) Channels in Primary Sensory Neurons for Bone Cancer Pain in a Rat Model

Kai-Zheng Duan, Qian Xu, Xiao-Meng Zhang, Zhi-Qi Zhao, Yan-Ai Mei, Yu-Qiu Zhang

Pain. 2012 Mar;153(3):562-74.

PMID: 22188869

Abstract:

Cancer pain is one of the most severe types of chronic pain, and the most common cancer pain is bone cancer pain. The treatment of bone cancer pain remains a clinical challenge. Here, we report firstly that A-type K(+) channels in dorsal root ganglion (DRG) are involved in the neuropathy of rat bone cancer pain and are a new target for diclofenac, a nonsteroidal anti-inflammatory drug that can be used for therapy for this distinct pain. There are dynamically functional changes of the A-type K(+) channels in DRG neurons during bone cancer pain. The A-type K(+) currents that mainly express in isolectin B4-positive small DRG neurons are increased on post-tumor day 14 (PTD 14), then faded but still remained at a higher level on PTD 21. Correspondingly, the expression levels of A-type K(+) channel Kv1.4, Kv3.4, and Kv4.3 showed time-dependent changes during bone cancer pain. Diclofenac enhances A-type K(+) currents in the DRG neurons and attenuates bone cancer pain in a dose-dependent manner. The analgesic effect of diclofenac can be reversed or prevented by A-type K(+) channel blocker 4-AP or pandinotoxin-Kα, also by siRNA targeted against rat Kv1.4 or Kv4.3. Repeated diclofenac administration decreased soft tissue swelling adjacent to the tumor and attenuated bone destruction. These results indicate that peripheral A-type K(+) channels were involved in the neuropathy of rat bone cancer pain. Targeting A-type K(+) channels in primary sensory neurons may provide a novel mechanism-based therapeutic strategy for bone cancer pain.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP185529640	Pandinotoxin-Kα		185529-64-0	Price

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