Neuropathic pain is one of the most widespread and intractable of human complaints.Neuroinflammation is recognized to play key roles in the development and maintenance of neuropathic pain.Many cytokines and chemokines have been found to be involved in the neuroinflammation in both peripheral and central nervous system.CXCL1 [Growth-Related Oncogene (GRO) or keratinocyte-derived chemokines (KC)] is one chemokine in CXC family and was found to be expressed in dorsal root ganglion neurons and increased after spinal nerve ligation.But the expression of CXCL1 in spinal cord and the role in neuropathic pain have not been elucidated.Our previous study showed that TNF-α increased CXCL1 expression in cultured astrocytes.In the present study, we found that intrathecal injection of TNF-α induced pain hypersensitivity as well as CXCL1 upregulation in the spinal cord.In addition, spinal nerve ligation (SNL) induced persistent CXCL1 upregulation in the spinal cord, which started from day 3, peaked at day 10 and maintained for more than 21 days.Remarkably, CXCL 1 was colocalized with the astrocytic maker GFAP, but not with microglial marker OX42 or neuronal marker NeuN, indicating the expression of CXCL1 in astrocytes.Furthermore, spinal application of CXCL1 induced pain sensitization and Fos expression in the spinal cord neurons.Spinal administration of CXCR2 antagonist attenuated neuropathic pain behavior.Collectively, our results suggest that CXCL1-CXCR2 may be involved in the maintenance of neuropathic pain by regulating the astrocytic-neuronal interaction in the spinal cord following spinal nerve ligation.Inhibition of the CXCL1-CXCR2 may provide a new therapy for neuropathic pain management.