Electroacupuncture Alleviates Hyperalgesia and Anxiety-Like Behaviors in Pain Memory Model Rats Through Activation of GABAergic Neurons and GABA Receptor in the Rostral Anterior Cingulate Cortex

Abstract

Recent studies have confirmed that pain memory is often accompanied by negative emotions. Electroacupuncture (EA) can block the retrieval of painful memories, thereby alleviating the associated negative behaviors. However, the underlying mechanism is poorly understood. This study revealed that the effect of EA on pain memory-induced negative behaviors is related to the mediation of GABAergic neuron activity and GABA receptor expression in the rostral anterior cingulate cortex (rACC). Previous studies have shown that the rACC is a crucial area for regulating nociceptive behaviors and negative emotions in pain memory models. The GABAergic neurons and receptors in the rACC are largely involved in pain sensation and related effects. However, the relationships among pain memory, GABAergic neurons and receptors in the rACC have not been investigated. In this study, we established a pain memory model via secondary plantar cross-injection of carrageenan and EA treatment. Using chemogenetic methods and behavioral assessments of pain and negative emotion, we found that early excitation of GABAergic neurons in the rACC blocked the recall of pain memories and reduced anxiety-like behaviors in pain memory model rats. Furthermore, pharmacological methods revealed that excitation of GABAA and GABAB receptors in the rACC blocks hyperpathia associated with pain memory and pain-induced anxiety-like behaviors, while inhibition of GABAA and GABAB receptors reverses these effects. These results suggest that EA may alleviate pain and associated anxiety-like behaviors related to pain memories through the activation of GABAergic neurons and excitation of GABAA and GABAB receptors in the rACC.

Deciphering the brain-gut axis: elucidating the link between cerebral cortex structures and functional gastrointestinal disorders via integrated Mendelian randomization

“…The primary discovery reveals a significant association between FD and reduced cortical thickness in the rACC, suggesting a potential causal relationship. Neuroimaging research has increasingly focused on changes in brain function or structure associated with FD, with the rACC being of particular interest due to its central role in regulating emotions ( Boes et al, 2018 ), pain perception ( Sun et al, 2024 ), and cognitive functions ( Wang et al, 2022 ). FD manifests as upper abdominal pain, a burning sensation, bloating, and early satiety, and involves increased gastrointestinal sensitivity ( Enck et al, 2017 ).…”