Electroacupuncture alleviates chemotherapy-induced peripheral neuropathy and anxiety by reducing TRPC6/PKC-dependent activation of glutamatergic neurons in the paraventricular thalamic nucleus.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and painful side effect of cancer treatment that damages nerves in the hands and feet, often accompanied by anxiety. Researchers investigated whether electroacupuncture could help relieve these symptoms and discovered how it works in the brain. In this study, scientists created a mouse model of CIPN using the chemotherapy drug cisplatin over 21 days. They found that CIPN activated specific calcium channels (TRPC6 and PKC proteins) in a brain region called the paraventricular thalamic nucleus (PVT), which processes both pain sensations and emotions. This activation increased glutamate, an excitatory brain chemical that amplifies pain signals and anxiety. When researchers applied electroacupuncture treatment to the mice, it significantly reduced CIPN symptoms including neuropathic pain, loss of sensation in the paws, and anxiety-like behaviors. The electroacupuncture worked by blocking the TRPC6 calcium channels, which reduced calcium influx into nerve cells and decreased PKC activation. This led to less glutamate release in the PVT region. The treatment also prevented the loss of nerve fibers and specialized touch receptors (Merkel cells) in the skin. Importantly, electroacupuncture produced effects similar to a pharmaceutical drug (SAR7334) that blocks the same calcium channels, but without medication side effects. These findings help explain the biological mechanism behind acupuncture's effectiveness for chemotherapy-related nerve pain and anxiety, suggesting it could be a valuable complementary therapy for cancer patients experiencing these debilitating side effects. Patients interested in electroacupuncture for CIPN should seek treatment from a licensed acupuncturist with experience in oncology support care.

This preclinical study investigated electroacupuncture's mechanism in treating chemotherapy-induced peripheral neuropathy (CIPN) with comorbid anxiety. Researchers established a CIPN mouse model using 21-day cisplatin administration, validated through von Frey testing, adhesive removal, open-field, and elevated plus-maze tests. Results demonstrated that CIPN increased TRPC6 calcium channel and PKC proteins while activating glutamatergic neurons in the paraventricular thalamic nucleus (PVT). Electroacupuncture treatment significantly ameliorated neuropathic pain, cutaneous sensation impairment, anxiety-like behaviors, and prevented loss of intra-epidermal nerve fibers and Merkel cells in acral skin. Mechanistically, EA inhibited TRPC6 activation, reduced calcium influx, attenuated p-PKC levels, and decreased glutamate release in the PVT—effects comparable to pharmacological TRPC6/PKC inhibition with SAR7334. Clinical takeaway: This study provides neurobiological evidence supporting electroacupuncture as an effective intervention for CIPN and associated anxiety by modulating calcium-dependent glutamatergic neurotransmission in thalamic pain-emotion integration centers, identifying TRPC6/PKC as potential therapeutic targets.