Abstract
Paclitaxel-induced peripheral neuropathy (PIPN) and associated neuropathic pain are
the most common and serious adverse effects experienced by cancer patients receiving
paclitaxel treatment. These effects adversely impact daily activities and consequently
the quality of life, sometimes forcing the suspension of treatment and negatively
influencing survival. Patients are usually at high risk of developing PIPN if paclitaxel
induces acute pain, which strongly suggests that an acute increase in the excitability
of nociceptors underlies the chronic alterations of PIPN. KCNQ/Kv7 channels are widely
expressed in the primary sensory neurons to modulate their excitability. In the present
study, we show that targeting KCNQ/Kv7 channels at an early stage is an effective
strategy to attenuate the development of PIPN. We found that paclitaxel did not decrease
the expression level of KCNQ/Kv7 channels in the primary sensory neurons as detected
by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western
blotting. However, retigabine, which is a specific KCNQ/Kv7 channel opener, attenuated
significantly the development of PIPN, as shown by both morphologic and behavioral
evidence. We also observed that retigabine had no obvious effect on the chemosensitivity
of breast cancer cells to paclitaxel. Although retigabine has been approved by the
FDA as an anticonvulsant, our study suggests that this drug can be repurposed to attenuate
the development of PIPN.
Perspective
Paclitaxel-induced peripheral neuropathy and associated neuropathic pain are severe
and resistant to intervention. The results of our study demonstrated that retigabine
(a clinically available medicine) can be used to attenuate the development of paclitaxel-induced
peripheral neuropathy.
Key words
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Article info
Publication history
Published online: November 21, 2018
Accepted:
November 5,
2018
Received in revised form:
October 11,
2018
Received:
June 21,
2018
Footnotes
Supported by grants from the American Pain Society (Q.Y.), Mission Connect (Q.Y.), Department of Defense USAMRAA (Q.Y.), Craig H. Neilsen Foundation (Q.Y.), and NIH grants (CA208765 to Q.Y. and CA172129 to J.A.F.).
The authors declare no competing financial interests.
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© Published by Elsevier Inc. on behalf of the American Pain Society
