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Published on: September 26, 2018
Chronic Pain Synergizes With High-Fat Diet to Promote Cardiac Injury via c-Jun N-Terminal Kinase 1/Silent Information
Lan Wei1, Qiang Tao2, Shan You1
1Department of Anesthesiology Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai China.
Insights
Chronic pain worsens heart injury in hyperlipidemia by increasing inflammation and disrupting JNK1/Sirt1 signaling. This study highlights the synergistic cardiac risks of combined hyperlipidemia and chronic pain.
Area of Science:
- Cardiology
- Pain Medicine
- Molecular Biology
Background:
- Hyperlipidemia and chronic pain are known risk factors for cardiac injury.
- Cardiovascular diseases can arise from cardiac injury.
Purpose of the Study:
- To investigate the combined effects of hyperlipidemia and chronic pain on cardiac injury.
- To elucidate the underlying mechanisms of exacerbated cardiac injury.
Main Methods:
- Male apolipoprotein E-deficient mice were fed a high-fat diet and subjected to spared nerve injury to induce chronic pain.
- Cardiac function was assessed using echocardiography.
- Myocardial injury biomarkers, inflammatory cytokines, and lipid profiles were analyzed.
- JNK1 and Sirt1 expression in cardiac tissue was evaluated.
Main Results:
- Chronic pain did not significantly affect hyperlipidemia-induced metabolic changes.
- Chronic pain exacerbated cardiac injury, leading to impaired contractility, fibrosis, and inflammation.
- These cardiac changes were associated with dysregulated JNK1 activation and reduced Sirt1 expression.
Conclusions:
- Chronic pain synergistically worsens hyperlipidemia-induced cardiac injury.
- Inflammatory mechanisms and JNK1/Sirt1 signaling pathways are key mediators.
- Combined hyperlipidemia and chronic pain pose significant cardiovascular risks.
Background:
Both hyperlipidemia and chronic pain were recognized risk factors for cardiac injury, which could lead to cardiovascular diseases.
Methods:
Thirty-two male APOE-/- (apolipoprotein E-deficient) mice (C57BL/6 background, 1 month old) were randomly allocated to 4 groups (n=8/group): Sham group: high-fat diet+sham surgery for 3 months; P1 to P3 groups: high-fat diet +spared nerve injury-induced chronic pain initiated at 1, 2, or 3 months post high-fat diet commencement, respectively. Mechanical allodynia was induced via the spared nerve injury model. Pain thresholds were quantified using von Frey filaments. Anxiety-like behaviors were assessed via the Open Field Test. Transthoracic echocardiography was performed to measure left ventricular ejection fraction and fractional shortening. Serum biomarkers of myocardial injury, inflammatory cytokines and lipid profiles were analyzed by ELISA. Myocardial tissue sections were subjected to histopathological staining, immunohistochemistry, immunofluorescence, and Western blotting.
Results:
Chronic pain exerted negligible effects on high-fat diet-induced metabolic dysregulation, as evidenced by comparable levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides across all groups (P>0.05). In contrast, mice subjected to chronic pain (P1-P3 groups) exhibited significant deterioration in myocardial contractility, exacerbated fibrosis and collagen deposition, elevated cardiac injury biomarkers, and pronounced inflammatory cell infiltration compared with Sham group. These alterations correlated with dysregulated JNK1 (c-Jun N-terminal kinase 1) activation and suppressed Sirt1 (silent information regulator 1) expression in myocardial tissues.
Conclusions:
These findings demonstrated that chronic pain synergistically exacerbated hyperlipidemia-induced cardiac injury, primarily mediated through inflammatory mechanisms and JNK1/Sirt1 signaling dysregulation.
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