Pain: New Insights into Mechanisms, Diagnosis, Therapy, and Management

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Physiology and Pathology".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 2228

Special Issue Editors


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Guest Editor
College of Chinese Medicine, Graduate Institute of Acupuncture Science, China Medical University, Taichung 40402, Taiwan
Interests: pain; depression; TRPV1; signaling pathway; brain sciences
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Neurosurgery, China Medical University Hospital, Taichung 404328, Taiwan
Interests: neurosurgery; intensive care; spinal cord injury; pain

Special Issue Information

Dear Colleagues,

We have recently set up a Special Issue to attract articles on the topic of “Pain: New Insights into Mechanisms, Diagnosis, Therapy, and Management”.

Pain is defined as an uncomfortable feeling that activates nociceptive signals in both the peripheral and central nervous systems under clinical observation. The NIH has declared that chronic pain contributes the most to societal and economic costs and is implicated global healthcare expenditure.

Deep brain stimulation, artificial intelligence, nerve stimulation and neuroimaging, are among the new insights and approaches suggested for pain management. Furthermore, the use of cohorts, big data, and machine learning is becoming more prevalent in non-pharmacological treatment. We invite researchers and medical practitioners to submit original research or review articles focused on a range of methods that represent ongoing efforts to gain new insights into diagnosis mechanisms, therapy and management of pain for this upcoming Special Issue in the journal Life.

Prof. Dr. Yiwen Lin
Dr. I-Han Hsiao
Guest Editors

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Keywords

  • pain
  • mechanisms
  • signaling pathways
  • diagnosis

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Published Papers (2 papers)

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Review

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18 pages, 890 KB  
Review
Refractory Neuropathic Pain in the Head and Neck: Neuroanatomical and Clinical Significance of the Cervicotrigeminal Complex
by Marina Raguž, Marko Tarle, Koraljka Hat, Ivan Salarić, Petar Marčinković, Ivana Bičanić, Elvira Lazić Mosler, Ivica Lukšić, Tonko Marinović and Darko Chudy
Life 2025, 15(9), 1457; https://doi.org/10.3390/life15091457 - 17 Sep 2025
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Abstract
Refractory neuropathic pain of the head and neck remains a major clinical challenge, particularly when mediated through the cervicotrigeminal complex (CTC), a unique anatomical hub integrating trigeminal and upper cervical nociceptive inputs. This narrative review synthesizes neuroanatomical, pathophysiological, and clinical evidence to provide [...] Read more.
Refractory neuropathic pain of the head and neck remains a major clinical challenge, particularly when mediated through the cervicotrigeminal complex (CTC), a unique anatomical hub integrating trigeminal and upper cervical nociceptive inputs. This narrative review synthesizes neuroanatomical, pathophysiological, and clinical evidence to provide a unifying framework for diagnosis and management. A structured search of PubMed, Scopus, and Web of Science identified English-language clinical and mechanistic studies addressing CTC-mediated pain, with case reports excluded unless mechanistically informative. We propose multidimensional refractoriness criteria that integrate pharmacological non-response, failed interventional strategies, and objective functional impairment. Current treatments span pharmacotherapy, peripheral interventions (nerve blocks, radiofrequency ablation), and neuromodulation at multiple network levels (occipital nerve stimulation, spinal cord stimulation, motor cortex stimulation, deep brain stimulation). Non-invasive approaches such as rTMS, tDCS, and vagus nerve stimulation are emerging but remain investigational. Advances in imaging and neurophysiological biomarkers now permit greater precision in detecting CTC dysfunction and tailoring therapy. By combining anatomical precision, mechanistic insight, and multidisciplinary strategies, this review proposes a clinically actionable definition of refractoriness and supports a stepwise, mechanism-based approach to therapy. CTC emerges as a targetable hub for diagnostic and therapeutic strategies in refractory head and neck pain. Full article
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14 pages, 989 KB  
Systematic Review
The Effect of Physical Exercise on Non-Oncological Musculoskeletal Chronic Pain and Its Associated Biomarkers: Systematic Review on Randomized Controlled Trials
by Israel Castillo-Bellot, Ana María Peiró and Thomas Zandonai
Life 2025, 15(9), 1413; https://doi.org/10.3390/life15091413 - 8 Sep 2025
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Abstract
Objective: Non-oncological musculoskeletal chronic pain has a high prevalence and is a cause of disability, reduced quality of life, and significant economic impact. Physical exercise is presented as a treatment option; however, pain measurement remains a challenge, and various biomarkers are potential candidates [...] Read more.
Objective: Non-oncological musculoskeletal chronic pain has a high prevalence and is a cause of disability, reduced quality of life, and significant economic impact. Physical exercise is presented as a treatment option; however, pain measurement remains a challenge, and various biomarkers are potential candidates to objectify this process. This systematic review aims to study the effect of physical exercise on non-oncological musculoskeletal chronic pain and its associated biomarkers based on randomized controlled trials. Methods: A search for randomized controlled trials was conducted in the PubMed, Web of Science, and Scopus databases based on the established inclusion and exclusion criteria, along with a risk of bias assessment following the recommendations of the Cochrane Collaboration. Results: Five studies investigated various physical exercise interventions and their effects on biomarkers linked to chronic pain. Exercise consistently reduced self-reported pain, though no clear overall correlation with biomarker changes was found. However, significant associations emerged for specific biomarkers, particularly inflammatory markers and those identified through structural and functional brain imaging, suggesting potential mechanisms underlying pain modulation. Conclusions: The findings suggest that identifying chronic pain variations through biomarkers requires selecting markers linked to immune activity or brain processes. More randomized controlled trials with sufficient sample sizes and rigorous methodologies are needed. Despite this, physical exercise remains a valuable intervention for managing non-oncological musculoskeletal chronic pain. Additionally, it holds potential as a tool for uncovering novel biomarkers that may contribute to the objectification and understanding of chronic pain mechanisms. Full article
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