J Neuroinflamm
-
Pain is one critical hallmark of inflammatory responses. A large number of studies have demonstrated that stromal cell-derived factor 1 (SDF1, also named as CXCL12) and its cognate receptor C-X-C chemokine receptor type 4 (CXCR4) play an important role in immune reaction and inflammatory processes. However, whether and how SDF1-CXCR4 signaling is involved in inflammatory pain remains unclear. ⋯ The present results suggest that peripheral inflammatory pain state can trigger over release of SDF1 from the activated SGCs in the DRG by which SGC-neuronal cross-talk is mediated by SDF1-CXCR4 coupling that result in subsequent ERK-dependent Nav1.8 up-regulation, leading to hyperexcitability of tonic type of the primary nociceptor cells and development and maintenance of persistent spontaneous pain and hypersensitivity.
-
Macrophages persist indefinitely at sites of spinal cord injury (SCI) and contribute to both pathological and reparative processes. While the alternative, anti-inflammatory (M2) phenotype is believed to promote cell protection, regeneration, and plasticity, pro-inflammatory (M1) macrophages persist after SCI and contribute to protracted cell and tissue loss. Thus, identifying non-invasive, clinically viable, pharmacological therapies for altering macrophage phenotype is a challenging, yet promising, approach for treating SCI. Azithromycin (AZM), a commonly used macrolide antibiotic, drives anti-inflammatory macrophage activation in rodent models of inflammation and in humans with cystic fibrosis. ⋯ Taken together, these data suggest that pharmacologically intervening with AZM can alter SCI macrophage polarization toward a beneficial phenotype that, in turn, may potentially limit secondary injury processes. Given that pro-inflammatory macrophage activation is a hallmark of many neurological pathologies and that AZM is non-invasive and clinically viable, these data highlight a novel approach for treating SCI and other maladaptive neuroinflammatory conditions.