Nociceptive information is detected and transmitted by neurons in the dorsal root ganglion (DRG). Recently, single-cell RNA-sequencing has revealed the molecular profile of various cell types including fibroblasts in the DRG. However, the role of molecules in fibroblasts needs to be elucidated in nociceptive regulation. Here, we found that secreted modular calcium-binding protein 2 (SMOC2) was secreted by fibroblasts to become a component of basement membrane and envelop the unit consisting of DRG neurons and attached satellite glial cells (SGCs). Knockout of SMOC2 in both sexes of mice led to increased neuronal clusters and decreased mechanical threshold, but unchanged noxious thermal response. Knockdown of SMOC2 in the DRG phenocopied the behavioral performance by SMOC2 knockout in both sexes of mice. In vivo calcium imaging showed that SMOC2 knockout increased coupled activation of adjacent DRG neurons induced by nociceptive mechanical stimuli, which was reversed by DRG injection of SMOC2. Importantly, ...