Brain regions associated with pain perception also subsume those involved in emotional regulation, which likely constitutes the physiological basis underlying the comorbidity of pain and negative emotions. Acupuncture has unique advantages compared with drugs. Studies have shown that acupuncture can achieve multi-targeted and bidirectional regulation, simultaneously improving pain and accompanying negative emotional symptoms without causing drug resistance or systemic toxicity. In the hippocampus, acupuncture may contribute to the regulation of painful emotional memory processing by inhibiting ventral hippocampal neuron apoptosis, promoting neurogenesis, and regulating synaptic plasticity. In the anterior cingulate cortex, acupuncture may partially reduce the perception and transmission of pain-related emotions by inhibiting the release of glutamate and the expression of its receptors, enhancing the inhibitory effect of GABAergic receptors. In the medial prefrontal cortex, acupuncture might alleviate inflammatory responses by inhibiting microglial activation and the release of pro-inflammatory cytokines, thereby preserving the integrity of the descending regulatory circuit for painful emotions. This protects the integrity of the descending pain-emotion regulatory circuit. In the amygdala, acupuncture may improve reward deficiency and fear-related abnormal synaptic plasticity by regulating the expression of dopamine receptors, thus avoiding the excessive amplification of pain emotions. This article reviews the mechanisms by which acupuncture improves the induced negative emotions, which is helpful to promote the integration of acupuncture as a complementary approach into the precision medical treatment system for chronic pain-induced anxiety, depression, or comorbidities, and provides a scientific basis for the application of non-pharmacological therapies in neuropsychiatric disorders.
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