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

Abstract

AbstractBackgroundNeuropathic pain is difficult to treat in clinical practice, and the underlying mechanisms are insufficiently elucidated. Previous studies have demonstrated that Fcγ receptor I (FcγRI) 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-specificFcgr1conditional knockout (CKO) rats were established by crossing rats carrying aFcgr1loxP+/+with thePirtCRE+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 FcγRI-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 FcγRI. 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 FcγRI-related signaling.ConclusionsOur results indicate that the activation of neuronal CRP/FcγRI-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.