Association Between Early Postoperative Pain Burden and 30-Day Health-Related Quality of Life After Lumbar Spinal Fusion: A Multicenter Prospective Cohort Study

Abstract

Purpose

The relationship between early postoperative pain burden, quantified by the area under the pain score-time curve (AUC), and the recovery of health-related quality of life (HRQoL) after lumbar spinal fusion remains unclear. This study examined whether cumulative pain burden during the first postoperative week was independently associated with HRQoL at postoperative day (POD) 30.

Methods

This secondary analysis of a multicenter prospective cohort included 158 adults undergoing lumbar spinal fusion. HRQoL was assessed using the EQ-5D questionnaire at baseline and on POD 1, 3, 7, 14, 21, and 30. Pain intensity over the last 24 hours was assessed on POD 1, 3, and 7 using questions adapted from the Brief Pain Inventory. Early postoperative pain burden was quantified as the area under the pain score-time curve over POD 1, 3, and 7 using the trapezoidal method. The primary outcome was the EQ-5D index on POD 30.

Results

The median baseline EQ-5D index was 0.82 (interquartile range [IQR], 0.58 to 0.89). On POD 1, it declined to 0.05 (IQR, −0.02 to 0.11) and gradually recovered to 0.85 (IQR, 0.69 to 1.00) by POD 30. Median pain burden AUC was 17 (IQR, 11 to 22). Patients with higher pain burden demonstrated worse recovery trajectories and significantly lower EQ-5D on POD 30 (mean difference 0.18; 95% CI, 0.09 to 0.26; P < 0.001), and higher incidence of pain on POD 30 (65.7% vs 27.3%, P < 0.001). In multivariable analysis, early pain burden remained independently associated with poorer HRQoL (β = −0.007 per unit increase; 95% CI, −0.012 to −0.002; P = 0.005), along with hypoalbuminemia (β = −0.252; 95% CI, −0.368 to −0.135; P < 0.001) and longer surgical duration (β = −0.038 per hour increase; 95% CI, −0.066 to −0.011; P = 0.007). High pain burden also independently associated with pain presence on POD 30 (OR= 1.095; 95% CI, 1.040 to 1.153; P = 0.001).

Conclusion

Cumulative early postoperative pain burden independently predicts delayed HRQoL recovery at 30 days after lumbar spinal fusion, highlighting early pain management as a potentially modifiable target to improve postoperative recovery.

Introduction

Lumbar spinal fusion is one of the most commonly performed orthopedic procedures worldwide and is frequently associated with substantial postoperative pain.^1–3 Acute pain that is poorly controlled may persist beyond the expected period of tissue healing and evolve into chronic pain.^4,5 It has also been linked to impaired health-related quality of life (HRQoL), with moderate to strong inverse correlations between pain severity and both physical and mental well-being.⁶ In multivariable analyses, acute postoperative pain has consistently emerged as a key predictor of long-term pain and functional recovery after surgery.^5,7

Despite this, most studies assess pain at a single time point, which does not capture its dynamic course and may underestimate its overall impact.⁸ Both the intensity and duration of pain are likely to influence recovery.⁹ To better reflect this, we applied the concept of pain burden, defined as cumulative pain exposure over the early postoperative period (the area under the pain score-time curve).¹⁰ A growing body of evidence supports the use of pain burden and pain trajectory analyses to characterize postoperative pain and their clinical relevance.^11,12 For example, in patients undergoing major musculoskeletal surgery, persistent high pain trajectory is associated with poorer long-term quality-of-life outcomes.¹³ However, the relationship between early pain burden and early recovery outcomes remains poorly understood in patients undergoing spinal fusion.¹⁴

Although prior work has largely focused on outcomes at 3 or 12 months, the 30-day postoperative time point remains relatively underexplored. By this stage, primary tissue healing is generally complete, and 30-day outcomes are widely used as standard perioperative quality metrics, including within the World Health Organization Safe Surgery Saves Lives initiative.^15,16 Early recovery patterns at 30 days have also been shown to correlate with longer-term outcomes at 12 months.^17,18 Therefore, early postoperative pain burden may represent a potentially modifiable target for improving HRQoL during this critical recovery window and longer-term postoperative outcomes after lumbar spinal fusion.

In this study, we hypothesized that greater early postoperative pain burden would be independently associated with poorer HRQoL and a higher risk of persistent pain at postoperative day (POD) 30.

Methods

Study Design and Participants

This study is a secondary analysis of a multicenter, prospective cohort study investigating patient-reported postoperative pain and HRQoL outcomes. The original study was approved by the Ethics Committee of Peking University People’s Hospital (institutional review board approval No. 2018PHB229-02) and the ethics committees of all participating centers, and conducted in compliance with the Declaration of Helsinki. All participants provided written informed consent prior to enrollment. The study was conducted and reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.¹⁹

The inclusion criteria of the original cohort were as follows: adult patients aged ≥18 years who underwent selected surgical procedures under general or regional anesthesia and had a postoperative hospital stay of at least 1 day. Patients with a diagnosed psychiatric disorder, a history of opioid abuse, unable to provide written informed consent, inability to read or write, surgery cancellation, or those admitted to the intensive care unit (ICU) after surgery were excluded. In this secondary analysis, adult patients undergoing primary open lumbar spinal fusion for degenerative lumbar disease were identified from the original cohort. Patients without available primary outcome data at postoperative day (POD) 30 were excluded from the analysis.

Study Protocol

Patients were screened and eligible patients were approached by the investigators on the day before surgery. After written informed consent was obtained, baseline questionnaires were completed. Postoperative follow-up was conducted on postoperative days (POD) 1, 3, 7, 14, 21, and 30. Health-related quality of life was assessed using the EQ-5D-5L questionnaire and the EQ-visual analog scale (EQ-VAS).^20,21 The average pain score over the past 24 hours was assessed using a question adapted from the Brief Pain Inventory (BPI) questionnaire, which was standardized on a scale of 0 (no pain) to 10 (worst pain possible). Loss to follow-up was defined as the patient not being contacted during two consecutive follow-ups.

Perioperative Analgesic Management

The perioperative analgesic protocol was not standardized across participating centers. In general, all patients underwent general anesthesia with opioid-based intraoperative analgesia. Intraoperative corticosteroids (dexamethasone 5–10 mg or methylprednisolone 40–80 mg), dexmedetomidine infusion, and erector spinae plane block were used at the discretion of the anesthesiologist. All patients received opioid-based intravenous patient-controlled analgesia after surgery, and unless contraindicated, NSAIDs or selective COX-2 inhibitors were routinely administered during the first 48 hours.

Data Collection

Data were collected from both patient-reported questionnaires and medical records. Sociodemographic data, including age, sex and body mass index (BMI), were collected before surgery. Preoperative anxiety levels were assessed on a scale ranging from 0 (no anxiety) to 10 (severe anxiety). Health status prior to surgery included serum albumin levels (hypoalbuminemia was defined as a preoperative serum level of ≤35 g/L according to the Child-Pugh score), hemoglobin levels (anemia was defined as a hemoglobin level of ≤130 g/L in men and 120 g/L in women), and Charlson Comorbidity Index (CCI). Pain catastrophizing tendency was assessed using the Chinese version of the Pain Catastrophizing Scale (PCS).²² Preoperative chronic pain was defined as pain lasting at least 3 months prior to surgery. Postoperative variables relevant to recovery, including duration of surgery, time to first mobilization, time to first oral intake, and length of hospital stay, were also recorded. Postoperative complications of grade III or higher using the Clavien-Dindo Classification of Surgical Complications were defined as severe complications. On POD 30, the persistence of pain was defined as any patient-reported surgery-related pain.

Outcomes

The primary outcome was HRQoL on POD 30, assessed using the EQ-5D index score. Secondary outcomes included persistent postoperative pain on POD 30, time to first mobilization, time to first oral intake and length of stay after surgery.

Early postoperative pain burden was quantified as the area under the pain score-time curve (AUC) from POD 1 to 7 using the linear trapezoidal method (Supplementary figure). The AUC was calculated as:

which simplifies to:

where , , and Pain₇ represent the pain scores (range, 0–10) over the last 24 hours assessed on POD 1, POD 3, and POD 7, respectively.

Statistical Analysis

Statistical analyses were performed using SPSS version 26.0 (IBM Corp., Armonk, NY, USA). The Shapiro–Wilk test was used to assess the normality of continuous variables. Continuous variables were presented as mean ± standard deviation (SD) or median (interquartile range, IQR), and compared using t-test or Mann–Whitney U-test. Categorical variables were presented as number (percentage), and compared using chi-square test, or fisher’s test, if appropriate. The EQ-5D trajectories within 30 days after surgery were analyzed using a linear mixed-effects model.

For the longitudinal analysis of repeated EQ-5D measurements, missing values at POD 14 and POD 21 were imputed using the last observation carried forward (LOCF) method. No pain measurements were missing at the scheduled assessment time points (POD 1, POD 3, and POD 7) and no imputation was performed.

The association of early pain burden with HRQoL on POD 30 was analyzed using multivariable linear regression analysis, adjusting for potential patient- and surgery- related factors. After univariate analysis, factors with P < 0.10 were entered into the multivariable linear regression. Collinearity was assessed using variable inflation factor (VIF), with a VIF > 10 indicating significant collinearity. Regression coefficients are reported as unstandardized beta coefficients (β) with their 95% confidence intervals (CIs). Risk factors associated with persistent pain on POD 30 after surgery were analyzed with multivariable binary logistic regression analysis. Factors with P < 0.10 were entered into the final model, and estimates are reported as odds ratios (ORs) and 95% CIs. Internal validation was performed for regression model using the bootstrapping approach (n = 1000 samples). Receiver operating characteristic (ROC) analysis was performed to evaluate the ability of early pain burden to predict persistent pain on POD 30. All tests were two-tailed, and a P value < 0.05 was considered statistically significant.

Sample Size Calculation

This was a secondary analysis of a prospective cohort study. The sample size was determined by the original study and was not specifically calculated for the current analysis. A total of 158 patients were included in the final analysis. For the primary outcome, 14 potential risk factors were considered for the multivariable linear regression analysis, and the final model included 8 factors, yielding a subjects-per-variable ratio of approximately 20, which number was sufficient for multivariable linear regression analyses (>10 subjects per predictor).²³

Results

A total of 158 patients were included into final analysis (Figure 1), with 81 (51.3%) patients were male (Table 1). The mean age was 53 ± 15 years. The median baseline EQ-5D index and EQ-VAS were 0.82 (IQR, 0.58 to 0.89) and 70 (IQR, 58 to 80), respectively. On POD 1, the median EQ-5D index and EQ-VAS declined to 0.05 (IQR, −0.02 to 0.11) and 60 (IQR, 53 to 80), respectively, and gradually increased over time. On POD 30, scores were improved to 0.85 (IQR, 0.69 to 1.00) and 85 (IQR, 80 to 90), respectively. On POD 30, 70 patients (44.3%) reported persistent pain.

Figure 1.

Study flow diagram of patient selection.

Table 1.

Baseline and Perioperative Characteristics

Variables	n=158
Age (years)	53 ± 15
Sex, male	81 (51.3)
Body mass index (kg/m2)	23.1 ± 3.4
ASA physical status
I	23 (14.6)
II	127 (80.4)
III	8 (5.1)
Smoking	51 (32.3)
Previous surgical history	50 (31.6)
Anemia	46 (29.1)
Hypoalbuminemia	20 (12.7)
CCI	1 (0, 2)
Preoperative chronic pain	82 (51.9)
Anxiety score	1 (0, 3)
PCS score	14 (6, 20)
Preoperative EQ-5D index score	0.82 (0.58, 0.89)
Preoperative EQ-VAS	70 (58, 80)
Intraoperative medication
Corticosteroids	39 (24.7)
Dexmedetomidine	36 (22.8)
Nerve blockade	22 (13.9)
Surgical duration (hours)	3.3 (2.2, 4.8)
AUC of pain scores	17 (11, 22)

Note: Data are presented as mean ± SD, median (IQR) and number (percentage).

Abbreviations: ASA, American Society of Anesthesiologists; CCI, Charlson Comorbidity Index; PCS, Pain Catastrophizing Scale; EQ-5D, EuroQol 5-dimension questionnaire; EQ-VAS, EuroQol visual analogue scale.

The median AUC of pain scores during the first 7 days after surgery was 17 (IQR, 11 to 22). Patients were stratified into high and low AUC groups based on the median AUC value. EQ-5D trajectories in two groups were shown in Figure 2. For the EQ-5D index, a significant group-by-time interaction was observed (P < 0.001), and the mean difference between groups on POD 30 was 0.18 (95% CI 0.09 to 0.26, P < 0.001). Patients in the high AUC group showed consistently poorer outcomes across all EQ-5D dimensions (Supplementary Table 1). For EQ-VAS, no significant interaction was found (P = 0.357); the overall mean difference between groups across all time points was 6.94 (95% CI 5.23 to 8.66, P < 0.001). The primary and secondary outcomes between the two groups were presented in Table 2.

Figure 2.

Trajectories of pain scores during the first 7 postoperative days (A), EQ-5D index score (B) and EQ-VAS (C) during the first 30 postoperative days, comparing patients with high versus low pain burden (AUC groups). Data are presented as means ± SD (error bars). Differences in longitudinal trajectories were analyzed using linear mixed-effects models.

Abbreviations: AUC, area under the curve; EQ-5D, EuroQol 5-dimension; EQ-VAS, EuroQol visual analogue scale; POD, postoperative day.

Table 2.

Primary and Secondary Outcomes Between Low and High Pain AUC Groups

	Low AUC (n=88)	High AUC (n=70)	P value
Primary outcome
EQ-5D index score on POD 30	0.96 (0.78, 1.00)	0.78 (0.49, 0.95)	<0.001
Secondary outcome
EQ-VAS on POD 30	90 (80, 95)	84 (75, 90)	0.010
Incidence of pain on POD 30	24 (27.3)	46 (65.7)	<0.001
Length of hospital stay (days)	8 (7,14)	15 (10, 19)	<0.001
Time to first ambulation (hours)	116 (88, 165)	332 (110, 428)	<0.001
Severe complications on POD 30	0 (0)	0 (0)	—

Note: Data are presented as median (IQR) or n (%).

Abbreviations: EQ-5D, EuroQol 5-dimension questionnaire; EQ-VAS, EuroQol visual analogue scale; POD, postoperative day; AUC, area under the curve.

To identify factors associated with EQ-5D on POD 30, a linear regression analysis was performed. Patient and surgical related factors, including age, sex, BMI, smoking status, previous surgical history, anemia, hypoalbuminemia, preoperative chronic pain, CCI, anxiety score, Pain Catastrophizing Scale (PCS) score, baseline EQ-5D, surgical duration, and AUC of average pain during the first 7 days after surgery, were analyzed. Variables with P < 0.10 in univariate analysis were entered into the multivariate model. No evidence of multicollinearity was observed among the variables. In the multivariable analysis, hypoalbuminemia (β=−0.252, 95% CI −0.368 to −0.135, P < 0.001), longer surgical duration (per hour increase; β=−0.038, 95% CI −0.066 to −0.011, P = 0.007), and a higher AUC of pain (β=−0.007, 95% CI −0.012 to −0.002, P = 0.005) were independently associated with worse EQ-5D on POD 30 (Table 3). The bootstrap estimates (1,000 iterations) were highly consistent with those of the original model, supporting its internal validity and stability (Supplementary Table 2).

Table 3.

Univariate and Multivariate Linear Regression Analysis for EQ-5D Score at POD 30

Variables	Univariate Analysis		Multivariate Analysis
	β (95% CI)	P value	β (95% CI)	P value
Age (increase per 10 years)	0.003 (−0.027, 0.033)	0.841
Sex, male	−0.076 (−0.160, 0.009)	0.079	0.001 (−0.077, 0.078)	0.982
BMI (kg/m2)	0.022 (0.010, 0.034)	0.006	0.009 (−0.003, 0.020)	0.153
Smoking	−0.053 (−0.144, 0.038)	0.257
Previous surgical history	0.013 (−0.079, 0.105)	0.779
Anemia	−0.138 (−0.255, −0.021)	0.021	−0.009 (−0.065, 0.046)	0.865
Hypoalbuminemia	−0.303 (−0.422, −0.184)	< 0.001	−0.252 (−0.368, −0.135)	<0.001
CCI	0.011 (−0.026, 0.048)	0.565
Preoperative chronic pain	−0.002 (−0.089, 0.085)	0.963
Anxiety score	0.006 (−0.014, 0.026)	0.535
PCS score	−0.005 (−0.009, −0.001)	0.011	−0.002 (−0.006, 0.002)	0.279
EQ-5D baseline	0.171 (0.036, 0.307)	0.013	0.123 (−0.003, 0.250)	0.056
Surgical duration (increase per 1 hour)	−0.058 (−0.086, −0.031)	<0.001	−0.038 (−0.066, −0.011)	0.007
AUC of average pain	−0.011 (−0.016, −0.006)	<0.001	−0.007 (−0.012, −0.002)	0.005

Note: Age is presented per 10-year increase, and surgical duration per 1-hour increase. Bold text represents statistically significant values.

Abbreviations: BMI, body mass index; CCI, Charlson comorbidity index; PCS, Pain Catastrophizing Scale; EQ-5D, EuroQol 5-dimension questionnaire; AUC, area under the curve.

In the exploratory multivariable analysis, the association between pain score on POD 1 and the EQ-5D index on POD 30 was evaluated. Using the same covariate adjustment as in the primary analysis, pain score on POD 1 was not independently associated with the EQ-5D index on POD 30 (β=0.006, 95% CI: −0.015 to 0.027, P = 0.593). In addition, the model showed a lower adjusted R² than the primary model (0.254 vs, 0.290).

A logistic regression analysis was performed to determine the association between early pain burden and the presence of pain on POD 30. Factors with P < 0.10 in univariate analysis were entered into multivariate logistic model. After adjustment, a higher AUC of average pain remained independently associated with an increased likelihood of pain on POD 30 (OR= 1.095, 95% CI 1.040 to 1.153, P = 0.001) (Table 4). Bootstrap resampling (1,000 iterations) also demonstrated results consistent with those of the original logistic regression model, supporting the stability of the model estimates (Supplementary Table 3). Early pain burden (AUC) demonstrated a significant discriminative capacity, with an area under the receiver operating characteristic (ROC) curve of 0.727 (95% CI 0.646 to 0.809; P < 0.001). The optimal cut-off value, determined by the Youden index, was 17.5, yielding a sensitivity of 65.7% and a specificity of 72.7%. Patients with early pain burden above this threshold had a significantly higher risk of developing persistent pain compared with those below the threshold (65.7% vs 27.3%, P < 0.001).

Table 4.

Univariate and Multivariate Logistic Regression Analysis for Persistent Pain at POD 30

Variables	Univariate Analysis		Multivariate Analysis
	OR (95% CI)	P value	OR (95% CI)	P value
Age (increase per 10 years)	0.760 (0.607–0.952)	0.017	0.874 (0.536,1.426)	0.590
Sex, male	0.589 (0.313–1.111)	0.102
BMI (kg/m2)	0.873 (0.791–0.964)	0.007	0.954 (0.851,1.069)	0.418
Smoking	0.755 (0.386–1.475)	0.411
Previous surgical history	1.106 (0.564–2.169)	0.770
Anemia	1.950 (0.808–4.707)	0.137
Hypoalbuminemia	0.293 (1.106–0.808)	0.018	0.365 (0.122,1.093)	0.072
CCI score	0.716 (0.539–0.953)	0.022	0.904 (0.493,1.657)	0.744
Preoperative chronic pain	1.219 (0.643–2.311)	0.543
Anxiety	0.925 (0.797–1.075)	0.308
PCS score	1.027 (0.996–1.058)	0.092	1.021 (0.986,1.058)	0.241
Surgical duration (increase per 1 hour)	1.370 (1.251–1.500)	< 0.001	1.178 (0.907,1.530)	0.220
AUC of average pain	1.121 (1.098–1.144)	< 0.001	1.095 (1.040,1.153)	0.001

Note: Age is presented per 10-year increase, and surgical duration per 1-hour increase. Bold text represents statistically significant values.

Abbreviations: BMI, body mass index; CCI, Charlson comorbidity index; PCS, Pain Catastrophizing Scale; AUC, area under the curve.

Discussion

In this secondary analysis, we found that higher early pain burden during the first week after surgery was independently associated with worse EQ-5D scores and a higher risk of persistent pain at POD 30. These findings suggest that cumulative pain exposure during the early postoperative period has a sustained impact on subsequent recovery outcomes.

Our study applied the concept of early postoperative pain burden, which represents a meaningful advance over conventional single time-point pain assessment. Unlike isolated measurements that capture only transient pain intensity, the AUC approach integrates both intensity and duration, providing a more comprehensive estimate of pain experienced during the first week after surgery, which period is critical when pain is most dynamic and potentially modifiable.^14,24 Consistent with this rationale, our exploratory analysis showed that average pain on POD 1 was not independently associated with POD 30 EQ-5D, whereas cumulative pain burden remained an independent factor, suggesting that cumulative pain exposure may better reflect postoperative recovery than a single pain assessment. Compared with trajectory-based approaches, which require more complex longitudinal modeling and patient classification, the AUC-based metric provides a simple, quantitative summary that is readily applicable in clinical settings. This simplicity enhances its interpretability and feasibility, making it a practical tool for identifying patients at risk of suboptimal recovery.

We found that early pain burden was an independent risk factor for 30-day EQ-5D. From a clinical perspective, the per-unit regression coefficient (β = −0.007) should be interpreted in the context of the pain AUC scale. In the spinal surgery literature, the commonly cited MCID for EQ-5D of approximately 0.3 was established for long-term postoperative improvement and is not applicable to between-patient comparisons at a single time point. For cross-sectional differences, the general MCID for EQ-5D has been reported as 0.074.²⁵ In our cohort, the predicted EQ-5D difference between patients at the 75th and 25th percentiles of pain burden (AUC: 22 vs 11) was 0.077, exceeding this MCID threshold. These findings emphasize the clinical importance of effective perioperative pain management.

The association between greater early postoperative pain burden and poorer HRQoL is likely multifactorial. Poorly controlled pain in the early postoperative period can delay mobilization, which is critical for recovery. Previous studies have reported that each unit increase in average pain score is associated with a decrease in mobilization time of 0.12 hours per day.²⁶ Consistent with this, patients with high pain burden experienced an almost threefold increase in time to first postoperative ambulation in our study. Reduced early mobilization may lead to a cascade of adverse effects, including skeletal muscle loss and decreased exercise capacity.²⁷ In contrast, effective pain control promotes early mobilization, which in turn accelerates return of bowel function, reduces complications, and promotes overall recovery.^28,29 Consistently, we also observed a shorter length of stay in patients with lower pain burden. Furthermore, severe postoperative pain may adversely affect recovery through psychological and behavioral pathways, including psychological distress,³⁰ sleep disturbance,³¹ and pain-related fear avoidance,³² all of which may reduce participation in rehabilitation and negatively affect postoperative recovery.

Besides functional impairment, lower cumulative pain burden may also prevent the transition from acute to chronic postsurgical pain. High levels of acute postoperative pain, particularly during the latter half of the acute hospitalization period (48–96 hours), have been identified as a significant predictor of pain persistence at 30 days after surgery.¹⁸ The underlying mechanisms may involve central sensitization and maladaptive neuroplastic changes, which are induced by sustained nociceptive input during the early postoperative period.³³ In addition, the ROC analysis demonstrated that pain burden had moderate discriminative ability for predicting persistent pain at 30 days. Future studies incorporating multivariable prediction models that combine pain burden with other clinical and psychosocial factors are warranted to improve predictive accuracy and clinical utility.

In the present study, the median EQ-5D score at 30 days after spinal fusion was 0.85, suggesting that many patients were still in an intermediate stage of recovery.³⁴ Therefore, the combination of early pain burden assessment and 30-day EQ-5D evaluation is clinically meaningful for identifying patients at risk of suboptimal recovery and highlights a potential window for early intervention. Patients with high early pain burden may benefit from intensified or individualized analgesic strategies. In addition, we found that hypoalbuminemia is one of the strongest predictors of poorer HRQoL. Hypoalbuminemia is a marker of poor nutritional status and frailty, identifying patients with preoperative hypoalbuminemia may facilitate targeted nutritional optimization and multidisciplinary prehabilitation programs before surgery, thus potentially improving postoperative recovery.³⁵

In this study, persistent pain was defined as any patient-reported surgery-related pain at POD 30 according to the prespecified study protocol, with the aim of capturing the presence of residual postoperative pain. Although this approach allowed the identification of patients with ongoing surgery-related pain, it may also have included those with only mild residual discomfort. Consequently, the prevalence of persistent pain may have been overestimated compared with definitions based on pain intensity thresholds or pain-related functional interference. Future studies should further evaluate whether alternative definitions of clinically significant persistent pain yield similar findings.

There are several limitations. First, the follow-up period was limited to 30 days after surgery, and no longer-term outcomes such as 3-month or 1-year outcomes were measured. Therefore, the sustained impact of early pain burden on long-term recovery remains uncertain and needs further investigation. Second, this study was a secondary analysis with a relatively modest sample size. Although significant associations were identified, differences in clinical practice, rehabilitation pathways and cultural perceptions of pain may limit the generalizability of the findings. Future large multicenter prospective studies are needed to validate these results. Third, the exclusion of patients with missing key outcome data may introduce selection bias. However, this approach was necessary to ensure the validity of multivariable analyses. In addition, although LOCF was applied only for intermittent missing EQ-5D values before POD 30, this approach may not fully capture changes in postoperative recovery over time and could introduce bias. Fourth, although perioperative analgesic management was described, it was not included in the primary regression model, as the aim was to evaluate the overall association between postoperative pain burden and HRQoL. Residual confounding related to analgesic management and unmeasured surgical factors cannot be excluded. In addition, as an observational study, the present findings should be interpreted as demonstrating an association rather than a causal relationship.

Conclusion

In conclusion, early pain burden, quantified as the area under the pain score-time curve during the first postoperative week, was independently associated with HRQoL at 30 days after spinal fusion. These findings suggest that early postoperative pain represents a critical and potentially modifiable window. Targeted pain management strategies during this period may improve short-term recovery and potentially influence longer-term outcomes. Larger prospective studies with extended follow-up are needed to confirm these findings and to determine whether reducing early pain burden leads to sustained clinical benefit.

Funding Statement

This work was supported by Research and Development Fund of Peking University People’s Hospital (RDE2024-14) and Investigator Initiated Research by Pfizer (WI246149). The funders had no role in any of the stages from study design to submission of the paper for publication.

AI Disclosure

The free version of ChatGPT (GPT-5.5) was employed in this study for linguistic polishing of the manuscript. No AI tool was used to create data, results, or original research content.

Authors confirm the originality and accuracy of all manuscript content and take full responsibility for the integrity of the whole content, including the accuracy of references.

Data Sharing Statement

The datasets used and analyzed in the current study are available from the corresponding author (Qingfen Zhang) on reasonable request.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.