Chronic pain, often accompanied by anxiety and depression, presents a significant clinical challenge. Up to 80% of individuals experiencing long-term pain also grapple with these emotional disorders, creating a cycle that worsens both prognosis and quality of life. Current treatments frequently prioritize pain intensity, often leaving the emotional components inadequately addressed.
Acupuncture, a traditional Chinese medicine practice, is increasingly recognized as a potential therapeutic option for pain management. It offers a drug-free approach for conditions like chronic back pain, migraines and arthritis, with clinical trials supporting its efficacy in both acute and chronic pain scenarios. Emerging research suggests acupuncture may also positively influence pain-induced negative emotions, though the underlying neural mechanisms have remained largely unclear.
Previous research has highlighted the role of the prefrontal cortex in integrating pain perception and emotional regulation. However, it wasn’t definitively known whether acupuncture’s effects were mediated through modulation of this brain region. Understanding this connection is crucial for developing more targeted and effective treatments.
Recent research, published in January 2025 in Acupuncture Research, sheds light on this relationship. Researchers at Shaanxi University of Chinese Medicine demonstrated that electroacupuncture significantly alleviated anxiety- and depression-like behaviors in a mouse model of neuropathic pain by modulating specific excitatory neurons within the brain. Using a combination of behavioral testing and chemogenetic manipulation, the team found that the therapeutic benefits of electroacupuncture depended on the activation of glutamatergic neurons in the ventrolateral orbital cortex, a region of the prefrontal cortex closely linked to emotional processing. This provides direct neural evidence connecting acupuncture with brain circuit modulation.
The study involved establishing a neuropathic pain model in mice through common peroneal nerve ligation. Behavioral assessments – including open field, elevated plus maze, forced swimming, and tail suspension assays – revealed that nerve injury induced persistent anxiety- and depression-like behaviors alongside increased pain sensitivity. Daily electroacupuncture was then administered for seven days at acupoints “Yanglingquan” (GV34) and “Xuanzhong” (GB34), commonly used in pain treatment.
The results showed that electroacupuncture markedly improved emotional behaviors without affecting locomotion, suggesting a genuine anxiolytic and antidepressant effect. To pinpoint the underlying mechanism, researchers selectively activated or inhibited glutamatergic neurons in the ventrolateral orbital cortex using chemogenetic tools. Artificially activating these neurons replicated the emotional benefits of electroacupuncture, while inhibiting them completely blocked the therapeutic effect.
Immunofluorescence analysis confirmed increased neuronal activation following electroacupuncture, demonstrating that excitatory prefrontal neurons are a critical neural substrate linking pain relief and emotional regulation.
“Chronic pain is not merely a sensory experience—it fundamentally alters emotional brain circuits,” explained a senior author of the study. “Our findings show that electroacupuncture can directly engage prefrontal glutamatergic neurons that are suppressed by long-term neuropathic pain. By restoring the activity of this circuit, emotional symptoms such as anxiety and depression can be alleviated. This provides a biological explanation for the clinical observation that acupuncture improves both pain and mood, and highlights its potential as a complementary strategy for treating complex pain-related disorders.”
These findings have significant implications for the treatment of chronic pain conditions complicated by emotional disturbances. By identifying a specific prefrontal neural circuit involved in pain-induced anxiety and depression, the study opens new avenues for precision neuromodulation therapies. Electroacupuncture, as a low-risk and non-pharmacological intervention, may offer a way to reduce reliance on antidepressants or opioids, particularly for patients experiencing both pain and mood disorders.
Further research, published in in Nature, adds to this understanding. This study investigated how electroacupuncture influences nociceptive-initiated and centrally maintained pain through changes in brain activation and functional connectivity in female adults with fibromyalgia. The findings suggest electroacupuncture modulates these pain pathways through a “bottom-up” sensory pathway, increasing activation of the primary somatosensory cortex and strengthening connectivity between somatosensory and insular regions. This contrasts with the “top-down” process observed in a sham treatment group, which showed reductions in widespread pain linked to decreased activity in the precuneus and precuneus-insula connectivity.
research from , as detailed in Frontiers in Neurology, indicates that acupuncture can modulate the emotional and motivational aspects of pain by influencing neural circuits within the limbic and reward systems. A study published in in MDPI also found that real acupuncture can increase functional connectivity between the ventral tegmental area/periaqueductal gray and the amygdala, correlating with decreased pain bothersomeness.
More broadly, these findings support an integrative neuroscience framework where traditional therapeutic techniques are evaluated and optimized through modern brain circuit analysis, potentially accelerating their translation into evidence-based clinical practice. This approach could lead to more personalized and effective treatments for chronic pain and its associated emotional challenges.
