Study design and ethics approval

This prospective, single-center cohort study was approved by our hospital’s Ethics Committee and conducted in accordance with the Declaration of Helsinki. Informed consent was obtained from all participants prior to data collection.

Participants selection

Inclusion criteria: (1) age over 40 years; (2) unilateral TKA due to primary knee OA; (3) residence in high-altitude regions (above 2,500 m); (4) ability to understand and complete relevant questionnaires.

Exclusion criteria: (1) bilateral TKA; (2) concurrent serious medical conditions significantly affecting pain, such as cancer, spinal cord injury, or other neurological pain disorders; (3) history of psychiatric disorders; (4) history of drug or alcohol abuse; (5) preoperative use of medications for central sensitization, such as pregabalin or duloxetine; (6) opioid use within one month before surgery; (7) history of previous surgeries on the same knee; (8) American Society of Anesthesiologists (ASA) status classification of III or above.

Confirmation of central sensitization

The Central Sensitization Inventory (CSI) was used to confirm the presence of central sensitization before surgery [17]. While quantitative sensory testing (QST) can assess central sensitization through external stimuli at affected or distant sites, it is costly, time-consuming, and invasive, limiting its practical application. The CSI, a validated tool for assessing musculoskeletal disorders, was chosen for this study due to its reliability, ease of use, and non-invasive nature, making it suitable for clinical practice [18]. It includes 25 items that evaluate the presence and severity of central sensitization symptoms using a 5-point Likert scale (0 = never, 1 = rarely, 2 = sometimes, 3 = often, 4 = always). A CSI score of ≥ 40 has been validated as the threshold for identifying central sensitization [18].

Participants enrolment and grouping

During the study period, 314 consecutive patients met the inclusion criteria. However, 84 patients were excluded based on the exclusion criteria. Specifically, 37 patients were unable or refused to complete the questionnaire, nine patients had neurological pain disorders, seven patients had a history of psychiatric disorders, five patients had a history of drug or alcohol abuse, ten patients had undergone previous surgical treatments on the affected knee, three patients had preoperative use of pregabalin, six patients had used opioids within one month prior to surgery, and seven patients had ASA status classification of III or above. Ultimately, 230 patients were included in the study, with 36 patients classified into the CS group (CSI score ≥ 40), while the remaining 194 patients were placed in the non-CS group (CSI score < 40). (Fig. 1).

To minimize potential confounding factors and ensure a balanced comparison between the CS and non-CS groups, propensity score matching (PSM) was applied. The propensity scores were calculated using a logistic regression model based on baseline covariates, including age, body mass index (BMI), gender, side of surgery, altitude of residence, occupation type, symptom duration, and preoperative VAS score. This matching process resulted in 32 patients in the CS group being matched with 32 patients in the non-CS group (Fig. 1).

Fig. 1

Participant enrolment and grouping flow diagram. TKA, total knee arthroplasty; CSI, Central Sensitization Inventory; CS, central sensitization

Data collection

Baseline data included the preoperative Central Sensitization Inventory (CSI) score, age, BMI, gender, side of surgery, altitude of residence, occupation type, symptom duration, Age-adjusted Charlson Comorbidity Index (ACCI), operative time, and preoperative pain level, assessed using the Visual Analog Scale (VAS, 0–10, 0 represents no pain and 10 represents the worst possible pain).

Postoperative data included VAS scores collected at 24, 48, and 72 h. The simplified Postoperative Nausea and Vomiting (PONV) impact scale [19], length of hospital stay, and cumulative opioid consumption were recorded at discharge, with opioid consumption calculated using a morphine milligram equivalent (MME) conversion tool. At the six month follow-up, chronic postoperative pain incidence and patient dissatisfaction were recorded. Chronic pain was defined as pain lasting at least three months after surgery, localized to the surgical area or related dermatomes, with other causes excluded [20].

Surgical procedure and postoperative management

All procedures were performed by the same experienced surgeon under general anaesthesia, without the use of a tourniquet. Primary TKA was performed using a standard medial parapatellar approach, with a cemented posterior-stabilized implant.

A multimodal blood-loss prevention approach was employed, including preoperative optimization of haemoglobin levels and administration of tranexamic acid (TXA) at a dose of 15 mg/kg, 15 to 20 min prior to surgery. For anaesthesia, adductor canal nerve blocks (ACBs) were administered by the anesthesiologist under ultrasound guidance using a single injection of 0.2% ropivacaine (15–30 mL). A periarticular injection (PAI) of a 60 mL cocktail consisting of saline, morphine sulfate, betamethasone sodium phosphate, betamethasone acetate, and ropivacaine was given. Prior to implant placement, 20 mL of the cocktail was injected posterior to the joint capsule, and another 20 mL was used to infiltrate the medial and lateral collateral ligaments. After implant placement, the remaining 20 mL was injected into the quadriceps muscle, its associated ligamentous structures, and surrounding subcutaneous tissues.

Postoperatively, patients were encouraged to initiate knee mobilization on the first day after surgery and progressively increase participation in rehabilitation activities. Pain management followed a multimodal analgesia strategy to minimize opioid consumption. A patient-controlled analgesia (PCA) pump was used for personalized pain control during the first 24–48 h, with opioids reserved for breakthrough pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) were prescribed regularly as part of the postoperative analgesia regimen.

For thromboembolic prophylaxis, low-molecular-weight heparin (LMWH) was administered for seven days, followed by direct oral anticoagulants (DOACs) for an additional two weeks. Routine opioid prescriptions were avoided, with opioids reserved for rescue analgesia based on individualized assessment. At discharge, patients were provided with oral NSAIDs for continued pain management.

Statistical analysis

All statistical analyses were conducted using SPSS software, version 22.0 (SPSS Inc., Chicago, IL, USA). Results for continuous variables were expressed as mean ± standard deviation or median (interquartile range), depending on their distribution. Categorical variables were presented as frequencies and percentages. Continuous variables were analyzed using either t-tests or Mann-Whitney U tests, based on the outcomes of normality testing, while categorical variables were compared using chi-square (χ²) tests. PSM was employed to reduce the effects of confounding variables between the CS and non-CS groups. Logistic regression was used to estimate propensity scores based on selected covariates, and a 1:1 matching strategy with a nearest-neighbour approach and a caliper width of 0.2 was applied. Post-matching comparisons were performed to evaluate differences in baseline characteristics and postoperative outcomes between the two groups. Statistical significance was determined with a P-value threshold of < 0.05.