Here, through immunofluorescence staining, calcium imaging, neural circuit tracing, patch-clamp recording, and optogenetics- or chemogenetics-based manipulations, we re-veal that the anteromedial thalamic nucleus (AM), as a pivotal nucleus of the anterior thalamic group, specifically regulates ACC<sup>CRH</sup> neurons via a glutamatergic pathway, forming an AM<sup>CaMKIIɑ</sup>-ACC<sup>CRH</sup> neural circuit that collectively drives the progression of pain-anxiety comorbidity. Here, CAMK2G is linked to Anxiety.