CXCL5 activates CXCR2 in nociceptive sensory neurons to drive joint pain and inflammation in experimental gouty arthritis. Gouty arthritis is a common inflammatory arthritis worldwide, triggered by monosodium urate crystals (MSU) in the joints. It causes severe pain and inflammation, affecting daily life. Current treatments, such as colchicine or corticosteroids, have significant side effects, especially in patients with comorbidities. New options like IL-1β neutralizing antibodies are available but have limitations. This study shows that CXCL5, a chemokine, activates CXCR2 on nociceptive sensory neurons, leading to TRPA1 activation, which causes hyperexcitability and pain. Neuronal CXCR2 also coordinates with neutrophil CXCR2 to promote neutrophil chemotaxis via CGRP and substance P. Neuronal CXCR2 deletion reduces joint pain, neutrophil infiltration, and gait impairment in gout models. CXCR2 is expressed in human dorsal root ganglion neurons, and CXCL5 is elevated in serum from gout patients. CXCL5 is a potent neutrophil chemoattractant that activates CXCR2, leading to TRPA1 activation and hyperexcitability in sensory neurons. Gβγ signaling is involved in CXCR2-mediated TRPA1 activation. CXCL5-induced pain occurs before leukocyte infiltration, suggesting direct action on sensory neurons. Neuronal CXCR2 contributes to gout arthritis pain, joint inflammation, and gait impairments. CXCL5 also promotes neurogenic inflammation and neutrophil chemotaxis via CGRP and SP release. CXCR2 is expressed in human DRG neurons, and CXCL5 levels are elevated in serum from gout patients, indicating a potential role in gout pain and inflammation. These findings highlight the importance of CXCL5-CXCR2-TRPA1 signaling in gout arthritis.CXCL5 activates CXCR2 in nociceptive sensory neurons to drive joint pain and inflammation in experimental gouty arthritis. Gouty arthritis is a common inflammatory arthritis worldwide, triggered by monosodium urate crystals (MSU) in the joints. It causes severe pain and inflammation, affecting daily life. Current treatments, such as colchicine or corticosteroids, have significant side effects, especially in patients with comorbidities. New options like IL-1β neutralizing antibodies are available but have limitations. This study shows that CXCL5, a chemokine, activates CXCR2 on nociceptive sensory neurons, leading to TRPA1 activation, which causes hyperexcitability and pain. Neuronal CXCR2 also coordinates with neutrophil CXCR2 to promote neutrophil chemotaxis via CGRP and substance P. Neuronal CXCR2 deletion reduces joint pain, neutrophil infiltration, and gait impairment in gout models. CXCR2 is expressed in human dorsal root ganglion neurons, and CXCL5 is elevated in serum from gout patients. CXCL5 is a potent neutrophil chemoattractant that activates CXCR2, leading to TRPA1 activation and hyperexcitability in sensory neurons. Gβγ signaling is involved in CXCR2-mediated TRPA1 activation. CXCL5-induced pain occurs before leukocyte infiltration, suggesting direct action on sensory neurons. Neuronal CXCR2 contributes to gout arthritis pain, joint inflammation, and gait impairments. CXCL5 also promotes neurogenic inflammation and neutrophil chemotaxis via CGRP and SP release. CXCR2 is expressed in human DRG neurons, and CXCL5 levels are elevated in serum from gout patients, indicating a potential role in gout pain and inflammation. These findings highlight the importance of CXCL5-CXCR2-TRPA1 signaling in gout arthritis.