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Associations of Preoperative Cerebrospinal Fluid Acetylcholine, BDNF, and IL-1β with Acute Postoperative Pain Across Educational Strata

Year: 2026

Type: article

Abstract: Purpose: Educational attainment is commonly used as a proxy for cognitive reserve, but whether associations between central pain-related biomarkers and acute postoperative pain differ across educational strata remains unclear. We examined associations of preoperative cerebrospinal fluid (CSF) acetylcholine (ACh), brain-derived neurotrophic factor (BDNF), and interleukin-1 beta (IL-1β) with postoperative pain and explored whether their shapes differed by educational attainment. Patients and Methods: This cross-sectional study included 160 adult male participants in China who underwent anterior cruciate ligament reconstruction between September 2014 and January 2016. Educational attainment was categorized as <15 or ≥15 years. Acute postoperative pain was assessed using a visual analog scale (VAS). CSF ACh, BDNF, and IL-1β were quantified by ELISA. Associations with VAS scores were examined using multivariable linear regression, generalized additive models (GAMs), and exploratory two-piecewise linear regression. Results: Eighty participants were included in each educational stratum. Linear regression identified an association between IL-1β and VAS scores (P=0.003), but not ACh (P=0.313) or BDNF (P=0.086). GAMs showed significant smooth-term associations for ACh (edf=1.017, P=0.015), BDNF (edf=2.000, P=0.023), and IL-1β (edf=4.454, P=0.004). The ACh function was essentially linear, whereas BDNF and IL-1β showed greater curvature. Education-stratified curves appeared flatter in the higher-education group. Two-piecewise models did not significantly improve model fit over standard linear models within educational strata (all likelihood-ratio P>0.05), providing no robust evidence of discrete thresholds. Conclusion: Preoperative CSF ACh, BDNF, and IL-1β were associated with postoperative pain patterns that differed in shape, with the clearest nonlinearity observed for BDNF and IL-1β. Differences across educational strata should be considered exploratory and require confirmation in larger, prospectively powered studies.

Source: Journal of Pain Research

DOI: 10.2147/jpr.s634240