Objectives: To investigate the expression levels of calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP), and beta-endorphin in the cerebrospinal fluid (CSF) and peripheral blood of patients with primary trigeminal neuralgia (TN). Patients and methods: We included 20 patients with primary TN who underwent percutaneous radiofrequency thermocoagulation and collected four types of samples from all of them: sample A: CSF samples; sample B: peripheral blood samples; sample C: peripheral blood samples collected one day before the operation; sample D: peripheral blood samples withdrawn one day after the operation. Another 20 CSF samples of patients with nervous system disease or gynecological disease were collected as a control (sample E). Samples A and B were obtained at the same time. We also evaluated the expression of CGRP, SP, beta-endorphin, and VIP by visual analog scale (VAS) scores one day before and one day after the operation. In addition, heart rate (HR) at baseline and at the time of sample collection, mean arterial pressure (MAP), and all side effects of the procedure were recorded. Results: Significance were found concerning about CGRP, SP, beta-endorphin, and VIP in TN patients and the controls (P< 0.001). The expression of CGRP, SP, and VIP in sample A was higher than that in sample E. However, the beta-endorphin level in sample A was lower than that in sample E. There was a positive correlation between sample A and B regarding the expression of CGRP, SP, beta-endorphin, and VIP (P< 0.01). There was no relationship between the time of disease onset and the expression of CGRP, SP, beta-endorphin, and VIP in sample A and sample B (P> 0.05). No difference was detected between the neuropeptides levels in samples B and C (P>0.05). Notably, VAS in sample D was significantly lower than that in sample C (P< 0.01). Finally, there was no difference between the intraoperative HR and MAP values in the studied samples. Conclusion: In primary TN patients, the blood levels of CGRP, SP, beta-endorphin, and VIP were associated with those in CSF samples. There was a significant difference between the levels of the four neuropeptides in CSF and control samples. Our results also indicated that the levels of neuropeptides in blood samples can be tested for those in CSF. The disease onset and duration exerted insignificant effects on the production and release of CGRP, SP, beta-endorphin, and VIP. (C) 2016 Elsevier B.V. All rights reserved.