Nociceptive information is detected and transmitted by neurons in the DRG. Glia cells in the DRG play important roles in nourishing DRG neurons and regulating somatosensory sensation. Our previous study reports that various cell types, especially fibroblasts, are contained in the DRG. Fibroblasts are the most common cells of connective tissue that secret proteins to form extracellular matrix and maintain structural integrity. However, the role of fibroblasts and their secreted proteins in somatosensory transmission still remains unclear.

This work entitled “Fibroblastic SMOC2 Suppresses Mechanical Nociception by Inhibiting Coupled Activation of Primary Sensory Neurons” was published online in Journal of Neuroscience on May 18, 2022. ZHANG Shuo and her colleagues, under the supervision of Drs. ZHANG Xu and LI Changlin at the Guangdong Institute of Intelligence Science and Technology, reveal that fibroblastic SMOC2 is a component of basement membrane and surrounds the unit consisting of DRG neuron and attached satellite glial cells. SMOC2 is required for inhibiting the coupled activation of adjacent DRG neurons through suppressing satellite glial P2X7 receptor and maintaining the basal mechanical nociceptive threshold in the DRG.

In this study, researchers found that SMOC2 was mainly expressed in fibroblasts in the DRG. SMOC2 was secreted to be a component of basement membrane and surrounded the unit consisting of DRG neuron and attached satellite glial cells. Functional studies showed that SMOC2 was required for maintaining the basal mechanical nociceptive threshold in the DRG. Loss of SMOC2 leaded to the increased coupled activation of adjacent DRG neurons induced by noxious mechanical stimuli. Furthermore, SMOC2 interacted with and suppressed satellite glial P2X7 receptor to inhibit the coupled activation of adjacent DRG neurons. Moreover, Peripheral inflammation caused decreased fibroblast cells and SMOC2, which might result in the increase of coupled activation of adjacent DRG neurons. This study reveals a critical role of fibroblast-secreted protein in maintaining nociceptive mechanical sensation.

This work was supported by the National Natural Science Foundation of China, the Special Fund for Science-Technology Innovation Strategy of Guangdong Province, Chinese Academy of Sciences, Science and Technology Commission of Shanghai Municipality, Innovation Fund for Medical Sciences of Chinese Academy of Medical Sciences and Shenzhen Sanming Project.

Proposed model for SMOC2 in regulating coupled activation of adjacent DRG neurons induced by noxious mechanical stimulation

Reference: https://www.jneurosci.org/content/42/20/4069.long