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Peer-reviewedCC BY-NCJournal of pain research

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

  • Xiaoyu Yang1
  • Lidong Su2
  • Tiantian Kong3
  • Ruyue Li4
  • Han Wang4
  • Ligang Shan5
  • Yanlong Liu6
  • Fan Wang7
7 affiliations
  1. 1Department of Anesthesiology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, 100035, People's Republic of China.
  2. 2Department of Anesthesiology, the Third Affiliated Hospital of Inner Mongolia Medical University, BaoGang Hospital, Baotou, 014010, People's Republic of China.
  3. 3Development and Reform Division, Xinjiang Medical University, Urumqi, 830017, People's Republic of China.
  4. 4Medical Neurobiology Lab, Inner Mongolia Medical University, Huhhot, 010110, People's Republic of China.
  5. 5Department of Anesthesiology, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, 361021, People's Republic of China.
  6. 6School of Mental Health, Wenzhou Medical University, Wenzhou, 325035, People's Republic of China.
  7. 7Beijing Hui-Long-Guan Hospital, Capital Medical University, Beijing, 100096, People's Republic of China.
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Abstract

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. 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. 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. 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.

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Cite

BibTeXRIS
BibTeX
@article{yang2026associations,
  title = {{Associations of Preoperative Cerebrospinal Fluid Acetylcholine, BDNF, and IL-1β with Acute Postoperative Pain Across Educational Strata.}},
  author = {Xiaoyu Yang and Lidong Su and Tiantian Kong and Ruyue Li and Han Wang and Ligang Shan and Yanlong Liu and Fan Wang},
  journal = {Journal of pain research},
  year = {2026},
  month = oct,
  doi = {10.2147/jpr.s634240},
  url = {https://europepmc.org/article/MED/42953803},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Associations of Preoperative Cerebrospinal Fluid Acetylcholine, BDNF, and IL-1β with Acute Postoperative Pain Across Educational Strata.
AU  - Xiaoyu Yang
AU  - Lidong Su
AU  - Tiantian Kong
AU  - Ruyue Li
AU  - Han Wang
AU  - Ligang Shan
AU  - Yanlong Liu
AU  - Fan Wang
PY  - 2026
DA  - 2026/10/24
JO  - Journal of pain research
DO  - 10.2147/jpr.s634240
UR  - https://europepmc.org/article/MED/42953803
AB  - 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. 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. 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. 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.
SN  - 1178-7090
ER  -