Neuronal C-Reactive Protein/FcγRI Positive Feedback Proinflammatory Signaling Contributes to Nerve Injury Induced Neuropathic Pain

Neuropathic pain is difficult to treat in clinical practice, and the underlying mechanisms are insufficiently elucidated. Previous studies have demonstrated that the neuronal Fc-gamma-receptor type I (Fc gamma RI) of the dorsal root ganglion (DRG) mediates antigen-specific pain. However, the mechanisms of neuronal Fc gamma RI in neuropathic pain remain to be explored. Here, it is found that the activation of Fc gamma RI-related signals in primary neurons induces neuropathic pain in a rat model. This work first reveals that sciatic nerve injury persistently activates neuronal Fc gamma RI-related signaling in the DRG, and conditional knockout (CKO) of the Fc gamma RI-encoding gene Fcgr1 in rat DRG neurons significantly alleviates neuropathic pain after nerve injury. C-reactive protein (CRP) is increased in the DRG after nerve injury, and CRP protein of the DRG evokes pain by activating neuronal Fc gamma RI-related signals. Furthermore, microinjection of naive IgG into the DRG alleviates neuropathic pain by suppressing the activation of neuronal Fc gamma RI. These results indicate that the activation of neuronal CRP/Fc gamma RI-related signaling plays an important role in the development of neuropathic pain in chronic constriction injury (CCI) rats. The findings may provide novel insights into the neuroimmune responses after peripheral nerve injury and suggest potential therapeutic targets for neuropathic pain.

Automated summary

Neuropathic pain is difficult to treat and its mechanisms are not well understood. This study shows that neuronal Fc gamma RI plays an important role in neuropathic pain.