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ACTIVATION OF KV7 (POTASSIUM CHANNELS) REDUCES PAIN HYPERSENSITIVITY IN A RAT MODEL OF CHEMOTHERAPY-INDUCED NEUROPATHY

Alawadh, Abdullah H., Aljumah, Abdullah M., Alshaikh, Abdullah, Alomar, Abdullah K., Alruwaydh, Abdulrahman

Background: Most chemotherapeutic agents have serious side effects that can lead to dose reduction or discontinuation of treatment. One of which is damage to the peripheral nervous system. This Neurotoxicity is usually accompanied by chronic peripheral pain mainly in upper and lower extremities. Mechanisms of such chemotherapy-induced neuropathic pain (CINP) are poorly understood, but many researches have suggested that it is directly related to hyperexcitability of peripheral neurons. Many ion channels are believed to be involved in this hyperexcitability, including Kv7, a subtype of voltage gated potassium channels. Aim: The aim of this stud was to test whether retigabine, a specific Kv7 opener used to treat epilepsy, which is also characterized by hyperexcitability, is effective in reducing CINP. Methods: CINP was induced by injecting Paclitaxel (2 mg/kg) (a common anti-cancer drug) 4 times to male Sprague Dawley rats (n=12). Two evoked pain behaviors were assessed, which are mechanical hypersensitivity/allodynia, and heat hypersensitivity/hyperalgesia. Retigabine (7 mg/kg) was then injected to test its effectiveness in reducing pain hypersensitivity. Results: IP administration of Retigabine had an analgesic effect on paclitaxel-induced mechanical allodynia in the rat model of CINP. Paclitaxel produced a significant reduction in withdrawal response threshold compared to the baseline latency, but after administration of retigabine the withdrawal threshold went back towards normal. However, paclitaxel did not show increase in heat sensitivity in this model. Conclusion: Our findings suggest that Kv7 channels are a good target for developing new analgesics to treat CINP. Keywords: Neuropathy; pain; chemotherapy; Paclitaxel; Retigabine; CINP; Kv7

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