Distinct Neuronal Functions In The Acc Regulating Pulpitis-Induced Pain

The aim of this study was to identify the central brain regions and types of neurons involved in pulpitis-induced pain modulation, as well as to further investigate the central mechanisms and potential analgesic targets for pulpitis-induced pain. In this study, we investigated the functional and structural plasticity of anterior cingulate cortex (ACC) pyramidal neurons, GABAergic neurons, and subgroups of GABAergic neurons during pulpitis-induced pain and further explored the molecular mechanism. This investigation utilized 10 types of transgenic mice and integrated multiple methodologies, including immunofluorescence staining, transmission electron microscopy, multichannel electrophysiological recordings, Golgi staining, in vivo fiber photometry, chemogenetics and single cell sequencing. All animal experimentation was approved by the Institutional Animal Care and Use Committee. The procedures conformed to the Guide for the Care and Use of Laboratory Animals issued by the National Institutes of Health. The present study reveals that glutamatergic and GABAergic neurons in the anterior cingulate cortex (ACC) exert contrasting regulatory roles in pulpitis-induced pain. Structural plasticity of ACC neurons was observed, as confirmed by Golgi staining and electron microscopy. Only chemogenetic stimulation of the ACC SST neurons(a subtype of GABAergic neurons ) produces significant pain relief, and the same analgesic effect can be achieved by administering somatostatin analogs to the ACC. This study emphasizes the ACC as a critical brain region involved in the modulation of pulpitis-induced pain,and a significant analgesic effect mediated by ACC SST neurons was observed, primarily through the release of somatostatin (SST).