IL-17 contributed to the neuropathic pain following peripheral nerve injury by promoting astrocyte proliferation and secretion of proinflammatory cytokines

Abstract

Central neuroinflammation is important in the pathophysiological processes of neuropathic pain following peripheral nerve injury. Recently, interleukin-17 (IL-17) has been detected in different inflammatory conditions of the central nervous system and contributes to neuropathic pain associated with multiple sclerosis, experimental autoimmune encephalomyelitis. The present study, based on the rat model of spinal nerve ligation, analyzed the infiltration of cluster of differentiation (CD)4+ T cells and the expression of IL-17 in the spinal cord during the maintenance phase of neuropathic pain, and investigated central inflammatory reaction and astrocyte activation. The results demonstrated that the infiltrated CD4+ T cells in the spinal cord increased in the rat model of spinal nerve ligation, and immunofluorescence staining demonstrated that the CD4+/IL-17+ cells were located at superficial laminae of spinal dorsal horn. This was accompanied by significant upregulation of IL-17. Furthermore, the mRNA expression levels of IL-1β and IL-6 were also significantly enhanced in model rats compared with the sham and control groups in the spinal dorsal horn. In vitro, the proliferation ability and secretion of proinflammatory cytokines notably increased in the IL-17-stimulated astrocytes. Results from the present study indicate that IL-17 may contribute to neuropathic pain by promoting the proliferation of astrocytes and secretion of proinflammatory cytokines in spinal nerve ligation-induced neuropathic pain.

Neuropathic Pain: Central vs. Peripheral Mechanisms

“…Resident astrocytes, as well as CD4 + T cells infiltrating the dorsal horn, secrete IL-17 following SNL. The resultant expression of IL-1β and IL-6 is, along with TNF-α, important in the maintenance of neuropathic pain [87][88][89]. ATP is released by injured dorsal horn neurons [90], whereupon microglial purinergic receptors are activated, leading to microglial proliferation and neuropathic pain [91-94, 95•].…”

Cytokines in Pain: Harnessing Endogenous Anti-Inflammatory Signaling for Improved Pain Management

“…In addition to macrophages, T cells may also be important in the mechanisms that underlie pathological pain. For instance, activated CD4 + T cells, specifically Th1 and Th17 cells, migrate to associated lumbar DRG and/or the lumbar spinal cord dorsal horn in animal models of sciatic nerve transection (47)(48)(49), spared nerve injury (50,51), partial sciatic nerve ligation (52,53), and sciatic nerve chronic constriction injury (54).…”

Secukinumab attenuates reactive astrogliosis via IL‐17RA/(C/EBPβ)/SIRT1 pathway in a rat model of germinal matrix hemorrhage

“…IL‐17A, secreted by immune cells, plays a vital role in the stroke pathophysiology. In addition to its pro‐inflammatory effect, IL‐17A has been shown to promote hyperproliferation and differentiation of various cell types; the most notable are Th17 cells and γδT cells due to their production of IL‐17A . After hemorrhagic stroke, macrophages become activated and secret IL‐23, which promotes the activation of γδT cells and Th cells .…”

“…In addition to its pro-inflammatory effect, IL-17A has been shown to promote hyperproliferation and differentiation of various cell types; the most notable are Th17 cells and γδT cells due to their production of IL-17A. 17,[45][46][47][48] After hemorrhagic stroke, macrophages become activated and secret IL-23, which promotes the activation of γδT cells and Th cells. 18 Due to the blood-brain barrier (BBB) rupture after hemorrhagic stroke, 49 IL-17A enters into the brain tissue through the serum.…”