Abstract
Neuropathic pain is among the most debilitating forms of chronic pain. Studies have suggested that chronic pain pathogenesis involves neuroimmune interactions and blood–spinal cord barrier (BSCB) disruption. However, the underlying mechanisms are poorly understood. We modeled neuropathic pain in rats by inducing chronic constriction injury (CCI) of the sciatic nerve and analyzed the effects on C-X-C motif chemokine 10 (CXCL10)/CXCR3 activation, BSCB permeability, and immune cell migration from the circulation into the spinal cord. We detected CXCR3 expression in spinal neurons and observed that CCI induced CXCL10/CXCR3 activation, BSCB disruption, and mechanical hyperalgesia. CCI-induced BSCB disruption enabled circulating T cells to migrate into the spinal parenchyma. Intrathecal administration of an anti-CXCL10 antibody not only attenuated CCI-induced hyperalgesia, but also reduced BSCB permeability, suggesting that CXCL10 acts as a key regulator of BSCB integrity. Moreover, T cell migration may play a critical role in the neuroimmune interactions involved in the pathogenesis of CCI-induced neuropathic pain. Our results highlight CXCL10 as a new potential drug target for the treatment of nerve injury–induced neuropathic pain.
Highlights
Neuropathic pain is caused by primary lesions or dysfunction in the nervous system, and it is among the most debilitating forms of chronic pain [1]
The results revealed that CXCR3 is expressed abundantly in the spinal cord, where it colocalized with NeuN, but not with GFAP or Iba1
We investigated the putative link between CXCL10/CXCR3 signaling-mediated blood–spinal cord barrier (BSCB) disruption and neuropathic pain
Summary
Neuropathic pain is caused by primary lesions or dysfunction in the nervous system, and it is among the most debilitating forms of chronic pain [1]. One thing that is clear is that peripheral nerve injury leads to neuropathic pain by triggering radical changes that affect multiple components of the pain signaling pathway [5, 6]. CXCL10 Contributes to Neuropathic Pain are involved in the pathogenesis of chronic pain states [7,8,9]. Accumulating evidence indicates that multiple proinflammatory mediators are released from injured nerve fibers and adjacent immune cells after nerve injury and that these mediators in turn promote central sensitization and behavioral hyperalgesia [5, 10]. Animal studies have shown that peripheral nerve injury induces circulating immune cells to enter the spinal cord parenchyma, a phenomenon that may contribute to pain-related behaviors during the development of neuropathic pain [11,12,13]
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