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Background <p>Carpal tunnel syndrome (CTS) is a common painful musculoskeletal disorder caused by inflammation and hypertrophy of the flexor retinaculum. Significant relationships exist between CTS, metabolic syndrome, smoking, and health-related factors, but the molecular mechanisms remain poorly understood.</p> Methods <p>This cross-sectional preliminary investigation was conducted at Al-Razi Hospital (Department of Orthopaedics), Kuwait, between October 2022 and September 2023. Tissue samples from the flexor retinaculum were collected following carpal tunnel release surgery from patients with symptomatic CTS. Seven groups were included: healthy control (n = 10), trigger finger (control for gene expression analysis; n = 10), CTS (n = 10), diabetic CTS (n = 9), hypertensive CTS (n = 7), dyslipidemic CTS (n = 7), and smoker CTS (n = 9). Expression levels of CTS-related genes (COL-I, COL-II) and inflammatory genes (TNF-α) were evaluated by reverse transcription-polymerase chain reaction (RT-PCR). Participants completed the Perceived Stress Scale (PSS), Pittsburgh Sleep Quality Index (PSQI), Disability of the Arm, Shoulder and Hand (DASH), Numeric Pain Rating Scale (NRS), and Satisfaction with Life Scale (SWLS) questionnaires. One-way ANOVA with Bonferroni post-hoc correction and Pearson correlation analyses were used, with adjustment for confounders using directed acyclic graphs (DAGs).</p> Results <p>A total of 62 participants (33 males, 29 females; mean age 54 ± 6.9&#xa0;years; mean BMI 28.2 ± 3.4&#xa0;kg/m<sup>2</sup>) were enrolled. Hand dysfunction was significantly greater in metabolic CTS and smoker groups versus CTS group (<i>p</i> &lt; 0.0001; 95% CI for DASH score: 15.224.6). Stress levels were significantly higher in smoker CTS (<i>p</i> = 0.024; 95% CI: 2.3–8.7) and hypertensive CTS groups (<i>p</i> = 0.013; 95% CI: 1.9–7.4) compared to CTS alone. The diabetic CTS group showed significant sleep disturbance (<i>p</i> &lt; 0.0001; 95% CI: 3.5–9.2) and increased pain (<i>p</i> &lt; 0.0001; 95% CI: 2.1–5.8) compared to CTS alone. Life satisfaction was significantly lower in diabetic and hypertensive CTS groups (<i>p</i> &lt; 0.0001; 95% CI for SWLS score reduction: -12.4 to -5.8). COL-I, COL-II, and TNF-α gene expression significantly increased in metabolic CTS and smoker groups (<i>p</i> &lt; 0.0001; 95% CI for fold-change: 1.8–3.4). Strong correlations were observed between gene expression and all health-related factors (r = 0.34–0.93, <i>p</i> &lt; 0.01).</p> Conclusions <p>This preliminary investigation demonstrates that hand dysfunction, stress levels, pain severity, and reduced life satisfaction in CTS patients are strongly associated with increased inflammation (tumor necrosis factor-alpha) and collagen gene expression (collagen type I and collagen type II) in patients with diabetes, hypertension, or dyslipidemia and smokers with CTS. These findings provide mechanistic insights into CTS pathophysiology. Further rigorous research with larger samples is needed to validate these preliminary findings.</p>

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Health-related factors and epigenetic alterations in metabolic comorbidities patients and smokers with carpal tunnel syndrome: a preliminary investigation of patient-derived samples

  • 期刊论文

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  • 发表日期：

    2026年5月20日

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  • Abdulaziz M. F. Shayea,
  • Asmaa Kh. AlRumaihi,
  • Alalyaa Kh. AlSabah

摘要

Background

Carpal tunnel syndrome (CTS) is a common painful musculoskeletal disorder caused by inflammation and hypertrophy of the flexor retinaculum. Significant relationships exist between CTS, metabolic syndrome, smoking, and health-related factors, but the molecular mechanisms remain poorly understood.

Methods

This cross-sectional preliminary investigation was conducted at Al-Razi Hospital (Department of Orthopaedics), Kuwait, between October 2022 and September 2023. Tissue samples from the flexor retinaculum were collected following carpal tunnel release surgery from patients with symptomatic CTS. Seven groups were included: healthy control (n = 10), trigger finger (control for gene expression analysis; n = 10), CTS (n = 10), diabetic CTS (n = 9), hypertensive CTS (n = 7), dyslipidemic CTS (n = 7), and smoker CTS (n = 9). Expression levels of CTS-related genes (COL-I, COL-II) and inflammatory genes (TNF-α) were evaluated by reverse transcription-polymerase chain reaction (RT-PCR). Participants completed the Perceived Stress Scale (PSS), Pittsburgh Sleep Quality Index (PSQI), Disability of the Arm, Shoulder and Hand (DASH), Numeric Pain Rating Scale (NRS), and Satisfaction with Life Scale (SWLS) questionnaires. One-way ANOVA with Bonferroni post-hoc correction and Pearson correlation analyses were used, with adjustment for confounders using directed acyclic graphs (DAGs).

Results

A total of 62 participants (33 males, 29 females; mean age 54 ± 6.9 years; mean BMI 28.2 ± 3.4 kg/m2) were enrolled. Hand dysfunction was significantly greater in metabolic CTS and smoker groups versus CTS group (p < 0.0001; 95% CI for DASH score: 15.224.6). Stress levels were significantly higher in smoker CTS (p = 0.024; 95% CI: 2.3–8.7) and hypertensive CTS groups (p = 0.013; 95% CI: 1.9–7.4) compared to CTS alone. The diabetic CTS group showed significant sleep disturbance (p < 0.0001; 95% CI: 3.5–9.2) and increased pain (p < 0.0001; 95% CI: 2.1–5.8) compared to CTS alone. Life satisfaction was significantly lower in diabetic and hypertensive CTS groups (p < 0.0001; 95% CI for SWLS score reduction: -12.4 to -5.8). COL-I, COL-II, and TNF-α gene expression significantly increased in metabolic CTS and smoker groups (p < 0.0001; 95% CI for fold-change: 1.8–3.4). Strong correlations were observed between gene expression and all health-related factors (r = 0.34–0.93, p < 0.01).

Conclusions

This preliminary investigation demonstrates that hand dysfunction, stress levels, pain severity, and reduced life satisfaction in CTS patients are strongly associated with increased inflammation (tumor necrosis factor-alpha) and collagen gene expression (collagen type I and collagen type II) in patients with diabetes, hypertension, or dyslipidemia and smokers with CTS. These findings provide mechanistic insights into CTS pathophysiology. Further rigorous research with larger samples is needed to validate these preliminary findings.