Neurexin‐2 is a potential regulator of inflammatory pain in the spinal dorsal horn of rats

Chronic pain is one of the serious conditions that affect human health and remains cure still remains a serious challenge as the molecular mechanism remains largely unclear. Here, we used label‐free proteomics to identify potential target proteins that regulate peripheral inflammatory pain and reveal its mechanism of action. Inflammation in peripheral tissue was induced by injecting complete Freund's adjuvant (CFA) into rat hind paw. A proteomic method was adopted to compare the spinal dorsal horn (SDH) in peripheral inflammatory pain (PIP) model rats with controls. Differential proteins were identified in SDH proteome by label‐free quantification. The role of screened target proteins in the PIP was verified by small interfering RNA (siRNA). A total of 3072 and 3049 proteins were identified in CFA and normal saline (NS) groups, respectively, and 13 proteins were identified as differentially expressed in the CFA group. One of them, neurexin‐2, was validated for its role in the inflammatory pain. Neurexin‐2 was up‐regulated in the CFA group, which was confirmed by quantitative PCR. Besides, intrathecal siRNA‐mediated knock‐down of neurexin‐2 attenuated CFA‐induced mechanical and thermal hyperalgesia and reduced the expression of SDH membrane glutamate receptors (eg mGlu receptor 1, AMPA receptor) and postsynaptic density (eg PSD‐95, DLG2). These findings increased the understanding of the role of neurexin‐2 in the inflammatory pain, implicating that neurexin‐2 acts as a potential regulatory protein of inflammatory pain through affecting synaptic plasticity in the SDH of rats.