Paclitaxel Inhibits KCNQ Channels in Primary Sensory Neurons to Initiate the Development of Painful Peripheral Neuropathy

Zizhen Wu, Gabor Toro, Guoying Xu, Danny Dang, Charmaine Prater, Qing Yang

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Cancer patients undergoing paclitaxel infusion usually experience peripheral nerve degeneration and serious neuropathic pain termed paclitaxel-induced peripheral neuropathy (PIPN). However, alterations in the dose or treatment schedule for paclitaxel do not eliminate PIPN, and no therapies are available for PIPN, despite numerous studies to uncover the mechanisms underlying the development/maintenance of this condition. Therefore, we aimed to uncover a novel mechanism underlying the pathogenesis of PIPN. Clinical studies suggest that acute over excitation of primary sensory neurons is linked to the pathogenesis of PIPN. We found that paclitaxel-induced acute hyperexcitability of primary sensory neurons results from the paclitaxel-induced inhibition of KCNQ potassium channels (mainly KCNQ2), found abundantly in sensory neurons and axons. We found that repeated application of XE-991, a specific KCNQ channel blocker, induced PIPN-like alterations in rats, including mechanical hypersensitivity and degeneration of peripheral nerves, as detected by both morphological and behavioral assays. In contrast, genetic deletion of KCNQ2 from peripheral sensory neurons in mice significantly attenuated the development of paclitaxel-induced peripheral sensory fiber degeneration and chronic pain. These findings may lead to a better understanding of the causes of PIPN and provide an impetus for developing new classes of KCNQ activators for its therapeutic treatment.

Original languageEnglish (US)
Article number4067
Issue number24
StatePublished - Dec 2022


  • DRG
  • KCNQ channels
  • neuropathy
  • paclitaxel
  • pain

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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