The high-affinity IgG receptor FcγRI modulates peripheral nerve injury-induced neuropathic pain in rats

Abstract

The Fc gamma receptor I (FcγRI; CD64) is the high-affinity receptor of the immunoglobulin G protein (IgG). It is usually expressed in immune cells and has recently been identified to distribute in the nervous system and play critical roles in various neurological disorders. Presently, the impacts of FcγRI in neuropathic pain was largely unknown. Here, we aimed to investigate the impacts of FcγRI in neuropathic pain through pain-related neurobehavioral studies and underlying mechanisms by biochemical methods in animal and cell models. Specifically, we first utilized the chronic constriction injury (CCI) rat model that displayed neuropathic pain related symptoms and signs, including thermal hyperalgesia and mechanical allodynia. These neurobehavioral defects were significantly attenuated by the anti-FcγRI antibody, which was associated with reduced levels of neuropeptide substance P, C3, and TNF-α. Furthermore, we validated our animal findings using the embryonically neural crest-originated PC12 cell model. We found that stimulation of the IgG immune complex led to increased levels of FcγRI and inflammatory mediators, which were attenuated by the anti-FcγRI antibody in these cells. Collectively, our results from animal and cell-based studies suggest that FcγRI is a critical player for peripheral nerve injury-induced neuropathic pain by mediating pain-related immunological events, which therefore may provide a new therapeutic target for protection against chronic pain.

Development of an Aptamer-Based Molecular Tool for Specifically Targeting Microglia via the CD64 Protein

“…CD64 is increasingly believed to be involved in neurological diseases. 38 The expression of CD64 in microglia is relatively low under normal physiological conditions but has been shown to be strongly upregulated in diseases such as Alzheimer's disease 39 and multiple sclerosis. 40 Therefore, the ZH-1c aptamer may exhibit a potential for the application as a detection tool in the diagnosis of CD64-associated diseases.…”

“…CD64 is increasingly believed to be involved in neurological diseases . The expression of CD64 in microglia is relatively low under normal physiological conditions but has been shown to be strongly upregulated in diseases such as Alzheimer’s disease and multiple sclerosis .…”

The Role of Microglia in Neuroinflammation of the Spinal Cord after Peripheral Nerve Injury

“…Finally, it has also been known for some time that microglia surrounding axotomized MNs accumulate immunoglobulin G by Fc receptor binding [85]. A recent "micro-report" suggests Fc gamma receptor 1 (FcgRI) is also upregulated in the dorsal horn and participates in nerve-injury-induced chronic pain [86]. These less explored signals could contribute to microglial activation and/or modulate its properties, perhaps resulting in different behaviors and functions over different cellular elements of the dorsal or ventral horn.…”

Targeting the high affinity receptor, FcγRI, in autoimmune disease, neuropathy, and cancer

“…IgG-IC/FcγRI signaling has been linked to both the pathogenesis [ 50 , 66 , 83 ] and disease-associated pain [ 8 , 52 , 53 ] in RA. Joint pain is a prominent clinical characteristic of RA, which is caused in part by synovitis and joint destruction [ 96 ].…”