Levels of preoperative cerebrospinal fluid pro-inflammatory mediators and chronic pain after total knee arthroplasty surgery

Jungo Kato, Reiko Murase, Rie Minoshima, Fanglin Lu, Tomoko Toramaru, Yasuo Niki, Shizuko Kosugi, Hiroshi Morisaki

Research output: Contribution to journalArticlepeer-review


Background: Patients undergoing total knee arthroplasty (TKA) surgery are at high risk of chronic postsurgical pain (CPSP). Accumulating evidence suggests an active role of neuroinflammation in chronic pain. However, its role in the progression to CPSP following TKA surgery remains unanswered. Here, we examined the associations between preoperative neuroinflammatory states and pre- and postsurgical chronic pain in TKA surgery. Methods: The data of 42 patients undergoing elective TKA surgery for chronic knee arthralgia at our hospital were analyzed in this prospective study. Patients completed the following questionnaires: brief pain inventory (BPI), hospital anxiety and depression scale, painDETECT, and pain catastrophizing scale (PCS). Cerebrospinal fluid (CSF) samples were collected preoperatively and concentrations of IL-6, IL-8, TNF, fractalkine, and CSF-1 were measured by electrochemiluminescence multiplex immunoassay. CPSP severity was ascertained, using the BPI, 6 months postsurgery. Results: While no significant correlation was observed between the preoperative CSF mediator levels and preoperative pain profiles, the preoperative fractalkine level in the CSF showed a significant correlation with CPSP severity (Spearman's rho = −0.525; p =.002). Furthermore, multivariate linear regression analysis revealed that the preoperative PCS score (standardized β coefficient [β]:.11; 95% confidence interval [CI]: 0.06–0.16; p <.001) and CSF fractalkine level (β: −.62; 95% CI: −1.10 to −0.15; p =.012) were independent predictors of CPSP severity 6 months after TKA surgery. Conclusions: We identified the CSF fractalkine level as a potential predictor for CPSP severity following TKA surgery. In addition, our study provided novel insights into the potential role of neuroinflammatory mediators in the pathogenesis of CPSP.

Original languageEnglish
Pages (from-to)1091-1101
Number of pages11
JournalActa Anaesthesiologica Scandinavica
Issue number8
Publication statusPublished - 09-2023
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Anesthesiology and Pain Medicine


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