New Treatment for the Cognitive and Emotional Deficits Linked with Paclitaxel-Induced Peripheral Neuropathy in Mice.

Abstract

Using male mice administered paclitaxel (PTX) to model chemotherapy-induced peripheral neuropathy (PIPN), this study evaluated the effects of hydrogen-rich water (HRW) on pain and neuropsychiatric comorbidities. HRW given once or twice daily for 3–7 consecutive days reduced mechanical and thermal allodynia. Kv7 potassium channels and the Nrf2–heme oxygenase-1–NQO1 antioxidant pathway were implicated in these analgesic effects. HRW also suppressed memory impairment and anxiety- and depressive-like behaviors associated with PIPN. In the prefrontal cortex, HRW normalized elevated p-ERK1/2, p-Akt, and 4-hydroxynonenal levels while enhancing antioxidant enzyme activity. These findings suggest HRW may be a safe and effective candidate for addressing both the nociceptive and cognitive-emotional dimensions of PIPN.

Mechanism

HRW exerts analgesic effects via Kv7 potassium channel modulation and activates the Nrf2–heme oxygenase-1–NQO1 pathway to reduce oxidative stress, thereby normalizing elevated p-ERK1/2, p-Akt, and 4-HNE in the prefrontal cortex.