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Effects of electroacupuncture at Zusanli on pain-perception-related brain nuclei in KOA mice: a study on cortical and subcortical c-fos expression.

Behavioral and brain functions : BBFยทFebruary 2026ยทAiwen Chen, Tiantian Zhao, Xiaofei Gao et al.
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Key Finding

Electroacupuncture at Zusanli reversed widespread pain-induced neuronal inhibition across cortical and subcortical brain regions while additionally activating pain integration networks, providing neural evidence for its analgesic mechanisms in inflammatory pain.

What This Means For You

Researchers investigated how electroacupuncture relieves pain by studying mice with knee osteoarthritis, a common condition causing chronic joint pain and inflammation. Scientists applied electroacupuncture to the Zusanli point (located on the hind leg in mice, equivalent to a point below the knee in humans) and measured both pain sensitivity and brain activity across multiple regions. The study found that electroacupuncture significantly increased pain thresholds, meaning the mice could tolerate more discomfort after treatment. Importantly, the researchers discovered that chronic pain suppresses activity in numerous brain regions involved in processing pain, emotion, and movement. Electroacupuncture reversed this suppression in key areas including the motor cortex, insular cortex, and several deep brain structures like the caudate putamen, lateral septal nucleus, nucleus accumbens, and amygdala regions. The treatment also activated additional brain areas that help integrate pain information. These findings suggest electroacupuncture works through multiple mechanisms: it directly reverses abnormal brain inhibition caused by chronic pain and activates brain networks that process and modulate pain signals. This research provides scientific evidence for why acupuncture may be effective for osteoarthritis pain and helps explain the brain pathways involved in pain relief. The study supports electroacupuncture as a viable treatment option for people suffering from chronic inflammatory pain conditions. If you're considering acupuncture for chronic pain, seek treatment from a licensed acupuncturist trained in electroacupuncture techniques.

Clinical Notes for Practitioners

This study examined cortical and subcortical mechanisms underlying electroacupuncture analgesia in a murine KOA model using c-fos immunohistochemistry as a marker of neuronal activation. Bilateral Zusanli electroacupuncture significantly increased mechanical pain thresholds measured by Von Frey testing. C-fos mapping revealed that chronic inflammatory pain induces widespread neuronal inhibition across multiple brain regions including motor cortex, insular cortex, secondary auditory cortex, caudate putamen, lateral septal nucleus, nucleus accumbens, and anterior cortical amygdaloid area. Electroacupuncture reversed c-fos downregulation in these regions and additionally upregulated expression in granular insular cortex, medial septal nucleus, and extended amygdala. Results suggest electroacupuncture analgesia operates through dual mechanisms: reversing pain-induced inhibition in striatal, limbic, and cortical areas while activating pain integration networks. This neural mapping provides potential targets for complementary TMS therapy and supports multi-level CNS modulation as the mechanism for electroacupuncture's analgesic effects in inflammatory pain conditions. Sample size and effect sizes were not specified.

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