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Circulating microRNAs differentiate nociceptive and nociplastic pain: An exploratory study
Hiroyuki Nishie1,2, Hideki Nakatsuka2, Kazunori Iwasa3
1Department of Advanced Oncology, Kawasaki Medical School, Kurashiki-City, Okayama 701-0192, Japan.
Neurobiology of Pain (Cambridge, Mass.)
|July 21, 2025
Summary
Circulating microRNAs (miRNAs) show potential for distinguishing nociceptive from nociplastic pain. Specific miRNAs like let-7a, miR-26a, and miR-16 may serve as biomarkers for pain classification and treatment monitoring.
Area of Science:
- Biochemistry
- Molecular Biology
- Pain Research
Background:
- Nociceptive and nociplastic pain have distinct mechanisms but are difficult to differentiate clinically.
- Circulating microRNAs (miRNAs) are emerging as potential biomarkers for objective, mechanism-based pain classification.
Purpose of the Study:
- To determine if specific circulating miRNAs can differentiate nociceptive pain in hip osteoarthritis (HO) from nociplastic pain in chronic primary pain (CPP).
- To assess the relationship between these miRNAs and clinical/psychological outcomes.
Main Methods:
- Plasma samples from patients with HO (n=13), CPP (n=11), and controls (n=7) were analyzed using microarray screening and real-time PCR.
- Pain intensity, disability, quality of life, and psychological factors were assessed.
- Decision tree modeling and ROC analysis were used for classification accuracy.
Main Results:
- A predictive model using let-7a, miR-26a, and miR-16 demonstrated strong performance (R²=0.677; AUC>0.94).
- Let-7a correlated with structural changes in HO; miR-26a related to pain traits in CPP; miR-16 decreased post-CBT.
- miR-126 and miR-146a were linked to post-surgical pain reduction in HO.
Conclusions:
- Circulating miRNAs may help differentiate nociceptive and nociplastic pain mechanisms.
- These findings support the potential of miRNA-based biomarkers for precision pain diagnostics and personalized management.
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