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bioRxiv · 10.1101/2022.08.30.505953

Neuronal C-Reactive Protein Mediates Neuropathic Pain by Activating Nociceptive FcγRI-Coupled Signaling

Liu, F.·Su, S.·Zhang, L.·Fang, Y.·Cui, H.·Sun, J.·Xie, Y.·Ma, C.
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Abstract

BackgroundNeuropathic pain is difficult to treat in clinical practice, and the underlying mechanisms are insufficiently elucidated. Previous studies have demonstrated that Fc{gamma} receptor I (Fc{gamma}RI) is expressed in the neurons of the dorsal root ganglion (DRG) and may be involved in chronic pain. MethodsChronic constriction injury (CCI) was used to induce neuropathic pain in rats. Primary neuron-specific Fcgr1 conditional knockout (CKO) rats were established by crossing rats carrying a Fcgr1loxP+/+ with the PirtCRE+ line. Behavioral and molecular studies were conducted to evaluate the differences between wild-type and CKO rats after CCI. ResultsWe first revealed that CCI activated neuronal Fc{gamma}RI-related signaling in the DRG. CCI-induced neuropathic pain was alleviated in CKO rats. C-reactive protein (CRP) was increased in the DRG after nerve injury. Intraganglionic injection or overexpression of the recombinant CRP protein in the DRG evoked pain accompanied and activated neuronal Fc{gamma}RI. CRP-evoked pain was significantly reduced in CKO rats. Furthermore, microinjection of native IgG into the DRG alleviated neuropathic pain and the activation of neuronal Fc{gamma}RI-related signaling. ConclusionsOur results indicate that the activation of neuronal CRP/Fc{gamma}RI-related signaling plays an important role in the development of pain in CCI. Our findings may provide novel insights into the neuroimmune responses after peripheral nerve injury and might suggest potential therapeutic targets for neuropathic pain.

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Liu, F., Su, S., Zhang, L., Fang, Y., Cui, H., Sun, J., Xie, Y., Ma, C.. 2022-09-02. Neuronal C-Reactive Protein Mediates Neuropathic Pain by Activating Nociceptive FcγRI-Coupled Signaling. https://doi.org/10.1101/2022.08.30.505953

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