Objective:To investigate the levels of chemokine 2 (CCL2), chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C-X3-C motif) ligand 1 (CX3CL1), and chemokine (C-X-C motif) ligand 10 (CXCL10) in the cerebrospinal fluid of patients with acute and chronic herpes zoster (HZ), and their correlation with the severity of neuropathic pain.Methods:A total of 60 patients with acute herpes zoster and postherpetic neuralgia (PHN) treated at the First Affiliated Hospital of Zhengzhou University from November 2022 to November 2023 were selected for a case-control study. These patients were divided into a HZ group ( n = 25) and a PHN group ( n = 35). The pressure pain threshold in the affected area was measured on the day of admission for all patients. The Visual Analogue Scale scores were evaluated in both groups. After lumbar puncture, 2 mL of cerebrospinal fluid was collected, and the levels of related chemokines in the cerebrospinal fluid were detected using the enzyme-linked immunosorbent assay. Results:In the HZ group, the levels of chemokines CXCL1 and CXCL10 were (24.84 ± 6.97) ng/L and (107.46 ± 28.29) μg/L, respectively, while in the PHN group, they were (20.51 ± 3.16) ng/L and (132.98 ± 30.92) μg/L. The differences in the levels of chemokines CXCL1 and CXCL10 between the two groups were statistically significant ( t = 2.91, -3.26, both P < 0.05). There were no statistically significant differences in the levels of chemokines CCL2 and CX3CL1 between the two groups ( t = 1.62, -0.23, both P > 0.05). The levels of CCL2, CXCL1, CX3CL1, and CXCL10 in both groups were negatively correlated with the pressure pain threshold (HZ group: r = -0.84, -0.78, -0.93, -0.86; PHN group: r = -0.71, -0.78, -0.94, -0.76, all P < 0.01). Conclusion:Higher levels of chemokines in the cerebrospinal fluid of patients with acute and chronic HZ are associated with more pronounced neuropathic pain. The neuro-immune inflammation involving chemokines may be correlated with the severity of neuropathic pain in acute and chronic HZ.