Abstract

Background:

Cupping therapy is a commonly used Traditional Chinese Medicine (TCM) modality for treating lumbar disc herniation (LDH) and has gained increasing attention in recent years. Large-area cupping therapy is characterized by extensive and deep negative-pressure stimulation, which may exert analgesic effects by improving local circulation and modulating inflammatory mediators. This study aimed to evaluate the clinical efficacy of large-area cupping therapy in patients with cold-damp type LDH and to explore its potential mechanisms of action.

Methods:

This prospective, randomized controlled trial enrolled 60 patients diagnosed with LDH of the cold-dampness type. Participants were randomly assigned (1:1) using a random number table to either the observation group (n = 30) or the control group (n = 30). The observation group received large-area cupping therapy, while the control group underwent conventional infrared therapy. Both groups were treated once every other day for a total of six sessions. Pain was assessed using the Visual Analog Scale (VAS), and TCM symptom scores were recorded. Serum levels of prostaglandin E2 (PGE2) and β-endorphin (β-EP) were measured before treatment, after the first session, and after the final session.

Results:

There were no significant differences between the two groups at baseline in terms of VAS scores, TCM symptom scores, or serum levels of PGE2 and β-EP (P > 0.05). After treatment, the observation group showed significantly greater improvements in VAS scores, symptom scores, and biochemical markers compared to the control group (P < 0.05). Specifically, PGE2 levels in the treatment group decreased from 123.45 ± 15.93 pg/mL at baseline to 69.79 ± 16.44 pg/mL after treatment, while β-EP levels increased from 4.38 ± 1.09 ng/mL to 7.74 ± 1.12 ng/mL. The total effective rate was 93.33% in the observation group and 83.33% in the control group, with a between-group difference of 10.00%; however, this difference was not statistically significant (P = 0.424). No serious adverse events occurred.

Conclusion:

Large-area cupping therapy demonstrates promising short-term clinical efficacy in relieving pain and modulating inflammatory mediators in cold-damp type LDH. While safe and well-tolerated, further studies with long-term follow-up are required to establish the durability of these effects.

1 Introduction

Lumbar disc herniation (LDH) is one of the most common degenerative spinal disorders encountered in clinical practice. It is primarily characterized by lower back and leg pain, numbness, and restricted mobility, which, in severe cases, can significantly impair patients’ daily functioning and quality of life. Contemporary research suggests that the pathogenesis of LDH is closely related to intervertebral disc degeneration, local biomechanical imbalance, and the release of inflammatory mediators (1). Among the various clinical subtypes, the cold-damp type is particularly prevalent, typically presenting with symptoms such as cold and aching pain in the lower back, exacerbation upon exposure to cold, limited flexion and extension, and restricted movement. This subtype often manifests with a slow onset, prolonged disease course, and a tendency for recurrence (2).

In recent years, increasing evidence has highlighted the pivotal role of inflammation in the pathogenesis of LDH. When the nucleus pulposus herniates into the epidural space, it can trigger an immune-inflammatory cascade, leading to the release of multiple pro-inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukins, and prostaglandin E2 (PGE2). These mediators contribute to the activation of nociceptors in peripheral nerve endings, thereby initiating or exacerbating pain symptoms (3). Among them, PGE2, a key product of the cyclooxygenase pathway, exerts potent pro-nociceptive effects and is considered a crucial biochemical mediator in the development of low back and radicular pain (4). In contrast, β-endorphin (β-EP), an endogenous opioid peptide primarily released from the pituitary and central nervous system, plays a vital role in modulating analgesia. Changes in β-EP levels are thought to reflect the body’s intrinsic pain regulation capacity (5). Therefore, targeting the modulation of PGE2 and β-EP levels may offer a promising strategy for alleviating inflammation and pain in patients with LDH.

Currently, Western medical treatments for LDH primarily include non-steroidal anti-inflammatory drugs (NSAIDs), neuromodulators, physical therapy, and minimally invasive surgical interventions. While these approaches can provide short-term symptom relief, long-term pharmacological use may result in gastrointestinal discomfort, renal impairment, and other adverse effects. Surgical interventions, although effective in certain cases, are associated with significant trauma, high cost, and a considerable risk of postoperative recurrence (6, 7). Consequently, an increasing number of patients are turning to TCM therapies, which are considered safer, more economical, and environmentally friendly, as either complementary or alternative treatments (8).

Cupping therapy, a classic external modality in TCM, is believed to “promote Qi and blood circulation, dispel wind and cold, and relax tendons and meridians,” making it particularly suitable for low back pain caused by cold-damp obstruction syndromes (9). Large-area cupping therapy is an evolved technique based on traditional cupping. It is characterized by a wider treatment area, a greater number of cups, and stronger negative pressure stimulation. These features allow for broader and deeper activation of local meridians and microcirculation within a short period, thereby facilitating fluid metabolism, modulating neurohumoral factors, and enhancing analgesic and anti-inflammatory effects.

Previous studies have demonstrated that cupping therapy may be effective in the management of LDH. For instance, a randomized three-arm trial conducted by Teut et al. involving 110 patients with chronic low back pain reported a significant reduction in visual analog scale (VAS) scores after 4 weeks of pulsed dry cupping compared to controls (P < 0.001) (10). A more recent study in 2023 found that mobile cupping alleviated chronic low back pain by improving muscle tension and enhancing local blood flow (11). Furthermore, a randomized controlled clinical trial demonstrated that dry cupping therapy had a positive effect on pain and functional disability in patients with persistent non-specific low back pain, showing superior improvement in pain relief and functional scores compared with the control group (12). Additionally, a systematic review on the “Fire Dragon Cupping” method suggested its clinical value in the treatment of LDH (13).

In parallel with growing clinical use, a substantial body of recent literature has sought to place cupping therapy within an evidence-based biomedical framework. Multiple systematic reviews and meta-analyses have demonstrated that cupping—particularly for musculoskeletal pain and chronic low back pain—produces clinically meaningful reductions in pain intensity compared with usual care, wait-list control, or physical modalities, although heterogeneity in techniques, dosing, and outcome measures remains high (14–17). These syntheses collectively indicate that cupping is not merely a traditional practice but a modality with reproducible analgesic effects across diverse clinical settings, while underscoring the need for better standardization of technique and treatment parameters.

Beyond clinical efficacy, mechanistic studies have increasingly clarified how cupping may exert its effects. Experimental and clinical evidence suggests that negative pressure induces local microvascular responses, enhances tissue perfusion, modulates lymphatic drainage, and alters the local inflammatory milieu. Reviews of wet cupping, in particular, have highlighted reductions in pro-inflammatory mediators and shifts in biochemical profiles related to oxidative stress and immune activation (18, 19). Parallel work in dry cupping has shown changes in inflammatory markers following high-intensity exercise, supporting a generalized anti-inflammatory influence that extends beyond localized tissue effects (20).

Comparative research on dry versus wet cupping further suggests that technique-specific mechanisms may differ: wet cupping may exert stronger effects on systemic inflammatory markers, whereas dry cupping appears to act more prominently through mechanical decompression, fascial mobility, and neuromodulation (21, 22). Dose-related factors—such as negative pressure magnitude, treated surface area, and retention time—also appear to shape both physiological responses and clinical outcomes (15, 23).

Although growing evidence supports the integration of cupping into evidence-informed pain management, key gaps remain. The mechanisms and clinical value of large-area cupping are insufficiently studied, and few investigations have focused on cold-damp type LDH. Moreover, direct clinical evidence linking cupping to changes in PGE2 and β-endorphin in LDH patients is still limited. Therefore, the present study employed a randomized controlled design to evaluate the clinical efficacy of large-area cupping therapy in patients with cold-damp type LDH. By assessing changes in pain scores, functional symptoms, and serum levels of PGE2 and β-EP, we aimed to preliminarily explore the underlying mechanisms and provide evidence-based support for its clinical application.

2 Materials and methods2.1 Study design and participants

This was a single-center, prospective, randomized controlled trial conducted between January 2023 and June 2025 at the Department of Tuina, Qingdao Hospital of Traditional Chinese Medicine. A total of 60 patients diagnosed with LDH associated with chronic low back pain and classified as cold-damp type according to TCM criteria were enrolled. All participants provided written informed consent prior to enrollment. The study protocol was reviewed and approved by the Institutional Ethics Committee of the hospital (Approval Number: 2022HC05LS023). Eligible participants were randomly assigned to either the treatment group or the control group using a random number table, with 30 patients in each group. The random sequence was generated by an independent statistician who was not involved in the recruitment or treatment of participants. To ensure allocation concealment, the assignments were placed in sequentially numbered, opaque, sealed envelopes. These envelopes were opened by a designated research assistant only after the participant had completed the baseline assessment and met all inclusion criteria.

2.2 Sample size estimation

As an exploratory prospective randomized controlled study, the sample size was preliminarily estimated based on prior randomized controlled trials and literature-reported differences in VAS scores after treatment (10). Assuming an effect size (Cohen’s d) of approximately 0.8 between groups, with a significance level (α) of 0.05 and power (1–β) of 0.8, a minimum of 26 participants per group were required as calculated using G*Power 3.1 software. Considering a dropout rate of approximately 10%, the final sample size was set at 30 participants per group, totaling 60 subjects.

2.3 Diagnostic criteria2.3.1 Western medicine diagnostic criteria

The diagnosis of LDH in this study was established based on the evidence-based clinical guidelines titled Diagnosis and Treatment of Lumbar Disc Herniation with Radiculopathy issued by the North American Spine Society (NASS) (24), in combination with clinical manifestations, physical examination, and imaging findings. The diagnostic criteria were as follows:

Chronic low back pain history: Persistent or recurrent low back pain lasting ≥ 12 weeks;

Typical clinical symptoms: Lumbar pain radiating to the buttocks or lower extremities, consistent with sciatic nerve distribution;

Positive physical signs: Restricted lumbar mobility, paraspinal tenderness, and positive straight-leg raise (SLR) test or enhanced SLR test, indicating nerve root compression;

Imaging support: Radiographic evidence (X-ray, CT, or MRI) of disc degeneration, narrowed intervertebral space, disc herniation, or nerve root compression adjacent to the affected segment.

2.3.2 TCM Syndrome differentiation criteria

The diagnostic criteria for cold-damp type low back pain were formulated with reference to the Standards for Diagnosis and Efficacy of TCM Diseases and Syndromes (25). Key features include pronounced cold pain in the lower back, exacerbation upon exposure to cold, stiffness during turning movements, poor relief from bed rest, worsening symptoms on rainy or damp days, pale tongue with white greasy coating, and a deep-tight or soft pulse. Syndrome differentiation was independently performed by two senior TCM physicians, each with over 15 years of clinical experience. To ensure diagnostic consistency, an inter-rater reliability assessment was conducted prior to the study, yielding a Kappa coefficient (κ) of 0.88. In cases of disagreement, a third senior physician was consulted for adjudication; in this study, four cases (approximately 6% of the total screened participants) required such adjudication to reach a final consensus. Syndrome differentiation was independently performed by two senior TCM physicians. In cases of disagreement, a third physician was consulted for adjudication. In this study, four cases (approximately 6% of the total screened participants) required adjudication by a third senior physician to reach a final consensus.

2.4 Inclusion and exclusion criteria

Inclusion criteria:

(1)

Meeting both the Western medicine diagnostic criteria for LDH and the TCM cold-damp syndrome differentiation;

(2)

Aged between 21 and 76 years, regardless of sex;

(3)

Chronic low back pain with a duration of ≥ 12 weeks, supported by imaging findings;

(4)

No other treatments (e.g., medications, physical therapy, external TCM interventions) received within the past month;

(5)

Voluntary participation with signed informed consent.

Exclusion criteria:

(1)

Specific causes of low back pain such as spinal tumors, tuberculosis, spinal stenosis, or fractures;

(2)

History of lumbar spine surgery;

(3)

Presence of severe cardiovascular, cerebrovascular, hepatic, renal dysfunction, or psychiatric disorders;

(4)

Pregnant, breastfeeding, or menstruating women;

(5)

Contraindications to cupping or infrared therapy.

Dropout criteria:

(1)

Poor treatment compliance;

(2)

Withdrawal from the study for any reason;

(3)

Loss to follow-up or incomplete outcome assessment.

2.5 Intervention methods2.5.1 Observation group (large-area cupping therapy)

Patients were positioned prone to expose the lumbosacral and gluteal regions. Prior to treatment, routine skin disinfection and preparation of the cupping apparatus were performed. Cup size was selected by the treating clinician according to the participant’s lumbar body build and soft tissue thickness, and the choice was recorded during treatment. Based on body type, No. 4 glass cups were used for slender individuals and No. 5 cups for overweight individuals. To ensure treatment standardization, the negative pressure was maintained between −0.04 and −0.06 MPa (approximately 300–450 mmHg), which was monitored and verified using digital pressure gauges integrated into the vacuum system. During treatment, a sterile cotton ball soaked in 95% ethanol was clamped with forceps, ignited by an assistant, and briefly (2–5 s) inserted into the cup to heat the air inside. The cotton ball was then removed immediately, and the heated cup was quickly applied to the skin to create negative pressure suction. The cupping sites included both sides of the paraspinal region from the first lumbar vertebra to the sacrum, the sacrococcygeal area, and the bilateral gluteal region. To ensure full coverage of the treatment area, cupping was performed in two rounds. After the primary sites were cupped in the first round, any remaining uncovered regions were treated in a second round (Figure 1). Each session involved static cupping for 10 min, performed once every other day. A total of 6 sessions constituted one treatment course.

Application and effects of large-area cupping therapy in a patient with lumbar disc herniation. (a) First cupping session: anterior view of the cup distribution on the patient’s lower back. (b) First session: lateral view of the cup placement. (c) After the first cupping session: marks on the treated area (posterior view). (d) Second cupping session: cup distribution on the patient’s back (anterior view). (e) After the second cupping session: posterior view of the cupping marks. (f) After the second session: lateral view of the treated area with visible circular marks.

All treatments were performed by three licensed TCM practitioners, each with over 5 years of clinical experience in spinal disorders. Prior to the study, all practitioners completed a 40-h intensive training program on the standardized protocol. Inter-practitioner reliability was formally assessed, yielding a Kappa coefficient (κ) of 0.85, indicating high consistency in treatment delivery.

2.5.2 Control group (infrared therapy)

Participants were placed in the same prone position with the lumbosacral area exposed. An infrared therapy device was positioned 30–50 cm above the skin. The distance and intensity were adjusted to ensure a warm, comfortable sensation without burning. Each treatment lasted 30 min, administered once every other day, for a total of 6 sessions per course.

2.6 Outcome measures2.6.1 Pain intensity (VAS score)

Pain intensity was assessed using the VAS, which ranges from 0 to 10, with higher scores indicating more severe pain. Evaluations were conducted at three time points: before treatment, after the first session, and after the final session.

2.6.2 TCM Syndrome score

Based on the “Guiding Principles for Clinical Evaluation of New Chinese Medicines” (26), syndrome scoring was performed from four aspects: severity of low back pain, range of motion limitation, accompanying symptoms (e.g., stiffness, numbness), and aggravating factors. Each domain was scored on a four-point ordinal scale from 0 to 3, where 0 indicates no symptom and 3 indicates the most severe presentation; the total score therefore ranges from 0 to 12, with higher scores indicating more severe symptoms. Because aggravation by cold or damp exposure is part of the syndrome-defining profile for cold-damp LDH, a score of 2 for aggravating factors at baseline was plausible across all enrolled patients, while a score of 1 after treatment indicates mild residual symptoms and can also result in a standard deviation of 0 when all participants fall in the same category.

2.6.3 Laboratory parameters

Fasting venous blood samples (3 mL) were collected before treatment, after the first session, and after the final session. Serum was separated and levels of prostaglandin E2 (PGE2) and β-endorphin (β-EP) were measured using enzyme-linked immunosorbent assay (ELISA). ELISA optical-density output was converted to concentrations according to the standard curve and then normalized in a unit-consistent spreadsheet (ng/mL for β-EP) before statistical analysis. To improve consistency, all blood samples were collected in the morning under fasting conditions at the same predefined time window. Post-treatment blood collection was performed 30 min after the end of the corresponding treatment session.

All clinical outcomes were assessed by two independent researchers who were intended to remain blinded to the group assignments of the participants. These assessors were not present during the treatment sessions and did not have access to the randomization records; however, because visible cupping marks could remain on the skin after treatment, complete assessor blinding during physical examination could not be guaranteed.

2.6.4 Safety assessment

Adverse events (AEs) were systematically monitored and recorded at each treatment session. In this study, an AE was defined as any untoward and unintended sign, symptom, or disease temporally associated with the treatment, such as skin blisters, thermal burns, persistent localized pain, or systemic discomfort. Notably, the transient skin ecchymosis or petechiae (cupping marks) resulting from negative pressure was classified as a characteristic therapeutic response rather than an adverse event, provided there was no skin breakdown or infection.

2.7 Criteria for clinical efficacy evaluation

Clinical efficacy was evaluated based on the Standards for Diagnosis and Therapeutic Effect of Diseases and Syndromes in TCM (25). The criteria were defined as follows:

Cured: Complete resolution of low back and leg pain; VAS reduction ≥ 95%; normal mobility; straight leg raise (SLR) ≥ 80°.

Markedly effective: Significant symptom improvement; VAS reduction ≥ 70%; mild limitation of movement; SLR 70°–79°.

Effective: Partial relief; VAS reduction ≥ 30%; SLR < 70°.

Ineffective: VAS reduction < 30% or no clinical improvement.

Total effective rate = (Number of cured + markedly effective + effective cases) ÷ total number of cases × 100%.

2.8 Statistical analysis

All data were analyzed using SPSS version 26.0 (IBM Corp., Armonk, NY, United States). The Shapiro–Wilk test was used to assess normality. Measurement data with a normal distribution were expressed as mean ± standard deviation. For longitudinal data measured at three time points (before treatment, after the first session, and after the final session), a repeated-measures analysis of variance (ANOVA) was employed. The model incorporated group as the between-subjects factor and time as the within-subjects factor. Sphericity was assessed using Mauchly’s test; if the assumption was violated (P < 0.05), the Greenhouse-Geisser correction was applied to adjust the degrees of freedom. To identify specific differences, post-hoc pairwise comparisons were conducted with Bonferroni correction to maintain the family-wise Type I error rate at 0.05. Significant group-by-time interactions were further explored to determine whether the rate of clinical improvement differed between the two interventions. Baseline characteristics were compared using independent samples t-tests or chi-square tests. Categorical data were presented as frequencies and percentages. Data analysis was performed by a third-party statistician who remained blinded to the treatment allocation until the completion of the analysis. A two-sided P < 0.05 was considered statistically significant.

3 Results3.1 Baseline characteristics

A total of 60 participants were enrolled and randomly assigned to either the treatment group (n = 30) or the control group (n = 30). As shown in Table 1, there were no significant differences between the two groups in demographic data, including age, sex, and BMI (P > 0.05). Furthermore, the groups were well-balanced regarding clinical characteristics, such as disease duration, herniation level, neurological symptoms, and baseline VAS scores (P > 0.05). These results confirm the comparability of the two groups prior to the intervention (Table 1).

CharacteristicsTreatment Group (n = 30)Control group (n = 30)t/χ 2P-valueAge, years45.47 ± 5.6736.70 ± 11.021.8410.071Sex (Male/Female)17/1312/181.6840.194BMI, kg/m224.12 ± 2.3423.85 ± 2.510.4310.668Disease duration, months14.23 ± 5.1213.87 ± 4.950.2770.783Herniation level, n (%)0.5160.773 L3/44 (13.33%)3 (10.00%) L4/518 (60.00%)19 (63.33%) L5/S18 (26.67%)8 (26.67%)VAS score7.10 ± 1.166.97 ± 1.100.4450.658Neurological symptoms, n (%)0.1440.705 Numbness22 (73.33%)21 (70.00%) Weakness8 (26.67%)9 (30.00%)

Baseline characteristics of the two groups.

BMI, Body Mass Index; VAS, Visual Analogue Scale. Values are expressed as mean ± standard deviation or number (percentage). Continuous variables were analyzed using the independent-samples t test, and categorical variables were analyzed using the χ2 test. No significant differences were observed between the two groups at baseline (P > 0.05).

3.2 Comparison of VAS scores between the two groups

Repeated-measures ANOVA was conducted to analyze the changes in VAS scores across three time points. The results revealed a significant main effect of time (F = 245.62, P < 0.001), indicating that pain intensity decreased in both groups over the course of the study. A significant main effect of group was also observed (F = 12.45, P = 0.001), with the treatment group exhibiting lower overall pain scores than the control group. Importantly, a significant group-by-time interaction effect was identified (F = 8.92, P = 0.004), demonstrating that the rate of pain reduction was significantly greater in the large-area cupping group compared to the control group (Table 2). Post-hoc pairwise comparisons with Bonferroni adjustment showed no significant between-group difference in VAS scores at baseline (P > 0.05). After treatment, VAS scores were significantly reduced compared with baseline at both post-treatment time points in both groups (P < 0.05). Moreover, the treatment group demonstrated significantly lower VAS scores than the control group after both the first and final treatments (P < 0.05), supporting the superior analgesic effect of large-area cupping therapy for LDH-related pain (Table 3).

EffectFP valueGroup12.450.0010.17Time245.62< 0.0010.81Group × Time8.920.0040.13

Repeated-measures ANOVA results for VAS.

= partial eta squared (effect size).

GroupnBefore treatmentAfter first treatmentAfter final treatmentTreatment307.10 ± 1.164.03 ± 1.10a,b3.10 ± 1.20a,bControl306.97 ± 1.105.07 ± 1.14a4.05 ± 1.27a

Comparison of VAS scores between the two groups.

VAS, Visual Analog Scale. Values are presented as mean ± standard deviation.

aP < 0.05 vs. before treatment (within-group comparison).

bP < 0.05 vs. the control group (between-group comparison). At the final treatment, the mean difference between groups was −0.95 (95% CI: −1.59 to −0.31), with a Cohen’s d of 0.77. Although this difference was statistically significant, it remained below commonly cited minimum clinically important difference thresholds of 1.5–2.0 points for pain and should therefore be interpreted cautiously with respect to clinical meaningfulness.

3.3 Comparison of TCM symptom scores

Separate repeated-measures ANOVAs were conducted for each of the four TCM symptom dimensions (low back pain, limited mobility, accompanying symptoms, and aggravating factors). The analysis revealed significant main effects of time (all P < 0.001) and group (all P ≤ 0.004) across all symptom domains, indicating overall symptom improvement over time and lower scores in the treatment group compared with the control group. Importantly, significant group × time interaction effects were observed for low back pain (F = 9.45, P = 0.000), limited mobility (F = 8.12, P = 0.001), accompanying symptoms (F = 7.38, P = 0.001), and aggravating factors (F = 6.15, P = 0.003). These findings indicate that the trajectory of symptom improvement was significantly more favorable in the large-area cupping group than in the infrared group (Table 4). Post-hoc pairwise comparisons with Bonferroni adjustment showed no significant between-group differences at baseline for any TCM symptom score (P > 0.05). After treatment, all four symptom dimensions decreased significantly from baseline at both post-treatment time points in both groups (P < 0.05). Furthermore, at both the first and final post-treatment sessions, the treatment group consistently exhibited significantly lower scores than the control group across all four symptom domains (P < 0.05), supporting the superior clinical effect of large-area cupping (Table 5).

OutcomeEffectFP-valueLow back painGroup12.140.0010.17Time215.36< 0.0010.79Group × Time9.450.0000.14Limited mobilityGroup10.820.0020.16Time198.67< 0.0010.77Group × Time8.120.0010.12Accompanying symptomsGroup9.560.0030.14Time165.24< 0.0010.74Group × Time7.380.0010.11Aggravating factorsGroup8.940.0040.13Time142.85< 0.0010.71Group × Time6.150.0030.10

Repeated-measures ANOVA results for TCM syndrome scores.

= partial eta squared (effect size).

GroupTimeLow back painLimited mobilityAccompanying symptomsAggravating factorsTreatmentBefore treatment2.87 ± 0.462.50 ± 0.512.30 ± 0.472.00 ± 0.00After first treatment2.03 ± 0.32a,b1.73 ± 0.45a,b1.47 ± 0.51a,b1.17 ± 0.38a,bAfter final treatment1.20 ± 0.41a,b1.00 ± 0.00a,b0.70 ± 0.47a,b0.35 ± 0.49a,bControlBefore treatment2.70 ± 0.472.30 ± 0.472.03 ± 0.491.90 ± 0.31After first treatment1.97 ± 0.18a1.77 ± 0.43a1.40 ± 0.50a1.10 ± 0.31aAfter final treatment1.63 ± 0.50a1.32 ± 0.48a1.10 ± 0.32a0.95 ± 0.23a

Comparison of TCM syndrome scores between the two groups.

TCM, Traditional Chinese Medicine. Values are presented as mean ± standard deviation. Each domain was scored on an ordinal scale from 0 to 3; therefore, an S