Abstract: Objective To explore the correlation between the levels of peripheral blood neurofilament light chain peptide (Nefl) and the severity of pain in cervical spondylotic radiculopathy (CSR), and assess whether Nefl can serve as a biomarker for the progression of CSR.Methods According to the random number table method, 18 healthy SD rats were divided into two groups (n=9): a Sham group and a chronic constriction injury (CCI) group. In the Sham group, the sciatic nerve was exposed and the skin was sutured. In the CCI group, the sciatic nerve was exposed and the skin was sutured after being looped. Then, their mechanical withdrawal thresholds (MWT) were measured by an electronic pain meter before operation and on post-operation days 1, 3, 7, and 14. Peripheral blood samples were collected for quantitative proteomic analysis. The levels of peripheral blood Nefl were detected by ELISA. Furthermore, 80 patients with CSR were selected as an experimental group, and 24 healthy individuals who underwent physical examination at the same time were selected as acontrol group. The visual analog scale (VAS) scores were collected, and the levels of Nefl protein in peripheral blood was detected by ELISA. The Spearman rank correlation coefficient method was used to evaluate the correlation between the levels of Nefl in peripheral blood and the severity of pain.Results Rats in the CCI group showed consistent declines in MWT before operation and on post-operation days 1, 3, 7, and 14, and its MWT values on post-operation days 3, 7, and 14 significantly lower than those in the Sham group (P<0.01). According to the TMT-marked quantitative proteomic analysis, Nefl resulted in significantly up-regulated protein expression, with Log(foldchange)=1.14 and P＜0.05. Furthermore, the rats in the CCI group presented consistent increases in Nefl protein contents of the peripheral blood before operation and on post-operation days 1, 3, 7, and 14. In contrast, the Sham group showed gradual decreases in Nefl protein contents on post-operation days 3, 7, and 14. There was a negative correlation between MWT and Nefl protein contents in the peripheral blood of rats (r=-0.662, P<0.01). CSR patients showed significantly higher expression of Nefl in the peripheral blood than that in healthy individuals (P<0.01). Patients with VAS score 8 presented significantly higher Nefl protein contents than those with VAS score 6 (P<0.01). There was a positive correlation between VAS and Nefl protein contents in the peripheral blood of rats (r=0.41, P<0.01).Conclusions The expression of Nefl significantly increases in the peripheral blood of CCI model rats and CSR patients, and is correlated with the severity of pain. Nefl can be used as a biomarker for evaluating the progression of CSR in clinical practice.