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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Clinical Rehabilitation".

Deadline for manuscript submissions: 15 August 2026 | Viewed by 6205

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Special Issue Editor

Dr. Eung Don Kim

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Guest Editor

Department of Anesthesiology and Pain Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Daejeon 34943, Republic of Korea
Interests: complex regional pain syndrome; erector spinae plane block; postherpetic neuralgia; sympathetic block; epidural block
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Special Issue Information

Dear Colleagues,

Pain is becoming an increasingly important issue in our society, especially as we enter an aging society. The appropriate management of chronic pain is becoming increasingly important in maintaining quality of life.

Although new pain treatment techniques and discoveries on pain mechanisms are being made, limitations still exist, and appropriate pain management is still a difficult topic.

We are looking for submissions on creative and novel ideas for pain management, from any department or specialty. We believe it is important to share and utilize ideas with each other, and through this, we hope to find opportunities to overcome the limitations of pain treatment that we are currently facing.

Dr. Eung Don Kim
Guest Editor

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

chronic pain
pain management
pharmacological treatment
non-pharmacological interventions
neuromodula-tion
multidisciplinary approaches
personalized medicine
quality of life

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Published Papers (4 papers)

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Research

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21 pages, 1011 KB

Open AccessArticle

The Role of Muscle Trigger Points in Chronic Whiplash-Associated Disorders with Neuropathic Pain Components: An Exploratory Cross-Sectional Study

by Marta Ríos-León, Andrés Barriga-Martín and Julian Taylor

J. Clin. Med. 2026, 15(9), 3361; https://doi.org/10.3390/jcm15093361 - 28 Apr 2026

Viewed by 302

Abstract

Background/Objectives: The role of muscle trigger points (TrPs) in neuropathic pain (NP) components in whiplash-associated disorders (WAD) has not been investigated. Our aim was to systematically investigate if referred pain elicited by trigger points (TrPs) in neck musculature reproduces neuropathic pain (NP) characteristics in chronic whiplash-associated disorders (WAD) and to determine the association of TrPs with pain intensity, mechanosensitivity, and disability. Methods: An exploratory cross-sectional study was conducted (n = 64; chronic WAD: n = 32; age- and sex-matched healthy controls: n = 32). TrPs in upper trapezius, suboccipital, splenius capitis, levator scapulae, scalene, and sternocleidomastoid muscles were evaluated. Pain intensity, NP components, pain catastrophizing, and disability were assessed with an 11-point numerical pain rating scale (0–10), NP questionnaires (Douleur Neuropathique 4 [DN4], self-administered Leeds Assessment of Neuropathic Symptoms and Signs [S-LANSS], and Neuropathic Pain Symptom Inventory [NSPI]), the Pain Catastrophizing Scale, and the Neck Disability Index, respectively. Mechanosensitivity (pressure pain thresholds) was assessed bilaterally over C2–C3 and C5–6 zygapophyseal joints, second metacarpal, and tibialis anterior muscle. The Mann–Whitney U test and advanced chi-square (χ²) test, including rank-based ANCOVA adjusted for age and sex, were used for comparisons between groups. Additionally, multivariate analyses were also performed (rank-based MANCOVA adjusted for age, sex, and pain intensity). Spearman’s rho (r_s) and LOESS regression analysis, corroborated with linear regression and/or polynomial regression coefficient analysis, were used to explore associations between clinical variables in WAD. Results: Significant differences in distribution of TrPs, with a significant effect of sex, were found between groups (p < 0.05). In WAD, a greater number of active TrPs, mostly prevalent in levator scapulae and suboccipital muscles, was associated with higher pain intensity, number and intensity of NP components, and disability (0.372 < r_s < 0.570, p < 0.05), or local mechanical hyperalgesia (r_s = −0.362, p < 0.05). Conclusions: Referred pain elicited by active TrPs in the neck muscles reproduced NP symptoms in chronic WAD. This study contributes to a new understanding of pain mechanisms in WAD, highlighting the role of active TrPs in generating or maintaining NP symptoms and sensitization processes. Full article

(This article belongs to the Special Issue New Insight into Pain and Chronic Pain Management)

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27 pages, 3416 KB

Open AccessArticle

Efficacy and Tolerability of Pridinol Mesylate Versus Quinine Sulfate in the Treatment of Nocturnal Leg Cramps: A Propensity Score-Matched Real-World Analysis of Depersonalized 4-Week Data from the German Pain e-Registry (PRISCILA Study)

by Michael A. Überall and Herbert Schreiber

J. Clin. Med. 2026, 15(5), 1708; https://doi.org/10.3390/jcm15051708 - 24 Feb 2026

Viewed by 587

Abstract

Background: Nocturnal leg cramps (NLCs) are common, especially in older adults, and may cause substantial distress, sleep disturbance, and functional impairment. Despite widespread clinical use of quinine sulfate (QUI), safety concerns limit its use. Pridinol mesylate (PRI), a centrally acting antispasmodic, may offer a promising alternative in clinical practice. Objective: To evaluate the clinical effectiveness and tolerability of PRI versus QUI in patients with NLCs. Methods: We conducted a retrospective, non-interventional, propensity score-matched analysis of anonymized routine data from 1722 adult patients (861 per group) with NLCs from the German Pain e-Registry (GPeR). Patients initiating either PRI or QUI between 2018 and 2023 were included. The primary outcome was a predefined composite responder rate (≥50% reduction in NLC frequency, duration, and affected nights, with no treatment discontinuation due to adverse drug reactions [ADRs] or inefficacy). Secondary outcomes included pain intensity, quality-of-life, disability, and ADR frequency. Results: PRI treatment resulted in a significantly higher responder rate (56.9%) compared to QUI (48.4%, p < 0.001; NNT = 12) due to greater short-term reductions in NLC episodes, duration, and pain intensity. The overall ADR rates were numerically higher with PRI (8.6%) than with QUI (6.7%), but discontinuation rates due to ADRs or inefficacy were comparable between groups and occurred in 3.1/2.6% with PRI/QUI (p = 0.865). Conclusions: In this large, real-world, propensity score-matched analysis, pridinol treatment was associated with a modest short-term advantage over quinine in several efficacy outcomes, while overall tolerability appeared broadly comparable. Given the retrospective, non-interventional design and the limited 4-week observation period, these findings should be interpreted as hypothesis-generating rather than confirmatory. Full article

(This article belongs to the Special Issue New Insight into Pain and Chronic Pain Management)

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Review

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28 pages, 1161 KB

Open AccessReview

κ-Opioid Receptor Agonists as Robust Pain-Modulating Agents: Mechanisms and Therapeutic Potential in Pain Modulation

by Mario García-Domínguez

J. Clin. Med. 2025, 14(20), 7263; https://doi.org/10.3390/jcm14207263 - 15 Oct 2025

Viewed by 3700

Abstract

Background/Objectives: κ-Opioid receptors have emerged as promising targets for novel analgesic strategies, offering the potential to relieve pain without the adverse effects commonly associated with μ-opioid receptor activation, such as respiratory depression, tolerance, and addiction. This review focuses on recent advances in understanding KOR-mediated pain modulation and aims to evaluate the therapeutic potential of KOR agonists in addressing the limitations of current opioid-based treatments. Methods: This review synthesizes evidence from comprehensive preclinical studies investigating the effects of KOR agonists on central pain pathways, including modulation of neurotransmitter release and attenuation of ascending nociceptive signaling. In addition, emerging clinical trial data on KOR-selective compounds will be evaluated, together with recent advances in biased agonism and region-specific receptor signaling, to guide the development of next-generation analgesics. Results: Preclinical studies demonstrate robust antinociceptive effects of KOR agonists, while early clinical trials indicate that several KOR-selective compounds effectively reduce pain symptoms. Advances in biased agonism and targeted receptor signaling suggest the potential to achieve analgesia with reduced dysphoria and sedation. Conclusions: KOR-targeted therapies show significant translational potential for pain management. The integration of preclinical and clinical evidence supports the development of next-generation KOR agonists that could provide effective analgesia while minimizing the adverse effects associated with conventional opioids. Full article

(This article belongs to the Special Issue New Insight into Pain and Chronic Pain Management)

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Other

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31 pages, 525 KB

Open AccessSystematic Review

Neurophysiological, Radiological, and Molecular Biomarkers of Pain-Related Conditions: An Umbrella Review

by Dmitriy Viderman, Sultan Kalikanov, Diyara Mukazhan and Bermet Nurmukhamed

J. Clin. Med. 2026, 15(2), 550; https://doi.org/10.3390/jcm15020550 - 9 Jan 2026

Viewed by 1145

Abstract

Background/Objectives: Pain and pain-related conditions are considered a global health and financial burden. In order to improve pain management, pain intensity assessment, and pain diagnosis, various biomarkers have been proposed. Since their clinical utility is not proven yet, the aim of this umbrella review is to synthesize existing evidence of all types of pain biomarkers available. Methods: Systematic searches were conducted in PubMed, Scopus, and the Cochrane Library from inception to 2 June 2025. Eligible studies were systematic reviews and meta-analyses examining any clinical, biochemical, genetic, neurophysiological, or imaging biomarker related to pain. The screening of studies, data extraction, and assessment of methodological quality using the AMSTAR-2 tool were conducted by two independent reviewers. Findings were summarized narratively. Results: A total of 49 systematic reviews and meta-analyses were included. Most reviews were rated as low or critically low quality. Inflammatory biomarkers (CRP, IL-6, TNF-α) reported the most consistent associations with chronic musculoskeletal pain, while neuroimaging and EEG measures reflected central nervous system alterations. Proteomic multi-protein panels demonstrated exploratory diagnostic potential, particularly for fibromyalgia, but lacked clinical validation. Evidence for genetic, hormonal, metabolic, neurochemical, and tissue-specific biomarkers was inconsistent and methodologically limited, supporting mechanistic rather than clinical inference. Conclusions: No single biomarker has achieved clinical validation for chronic pain, but several biomarker classes show promise. Future implications include high-quality longitudinal studies, standardized protocols, and multidimensional biomarker panels. Full article

(This article belongs to the Special Issue New Insight into Pain and Chronic Pain Management)

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