International Journal of Molecular Sciences

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Chronic Pain: Diagnosis, Pathophysiological Mechanisms and Treatment

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Dear Colleagues,

Chronic pain continues to be one of the most common illnesses, often without effective treatment options. The number of conditions, the concomitant involvement of different systems, and the personal characteristics of patients do not allow for standardized diagnostic and treatment procedures. Increases in human lifespan have certainly also increased the number of people in pain, alongside increases in personal, familial, societal, and economical burden. New drugs and treatments are available, but at present, patients too often go from one treatment to another without any possibility to resolve their pain.

With this Special Issue, we would like to collect evidence clarifying the present state of the art in chronic pain molecular pathology. Articles about the following are welcomed:

Sex differences in pain syndromes: clinical and laboratory evidence alongside molecular data;
Molecular mechanisms underlying age differences in pain syndromes: comparative studies in men and women;
Molecular diagnostic tools: new systems for old illnesses;
Molecular-based treatment approaches for pain.

Prof. Dr. Anna Maria Aloisi
Prof. Dr. Thomas Herdegen
Guest Editors

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Review

11 pages, 535 KiB

Open AccessReview

Fibromyalgia: Chronic Pain Due to a Blood Dysfunction?

by Anna Maria Aloisi and Ilenia Casini

Int. J. Mol. Sci. 2025, 26(9), 4153; https://doi.org/10.3390/ijms26094153 - 27 Apr 2025

Viewed by 138

Abstract

Fibromyalgia (FM) is a common chronic disorder with chronic pain. FM generally affects all ages and occurs more commonly in women. The cause of FM remains undefined, but a number of factors suggest the cardiovascular system and the blood in particular as contributors to its occurrence and maintenance. Hemograms and other blood indexes often show high percentages of values at the ‘normal’, low, or high limits and several values outside of the ‘normal’ ranges. On the other hand, vessels regulate blood arrival to tissues depending on many internal and external factors. Both aspects can interfere with tissue oxygenation and then with the numerous consequences induced by hypoxia. In this narrative review, efforts were made to highlight factors that are potentially able to affect oxygen arrival in cells, as well as other factors related to blood elements that can play a role in the chronic pain experienced by FM patients. Data strongly indicate that most of the symptoms commonly present in FM patients can find their physio-pathological basis in the blood, suggesting blood-related interventions in these patients. Full article

(This article belongs to the Special Issue Chronic Pain: Diagnosis, Pathophysiological Mechanisms and Treatment)

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27 pages, 1425 KiB

Open AccessReview

Clinical and Molecular Barriers to Understanding the Pathogenesis, Diagnosis, and Treatment of Complex Regional Pain Syndrome (CRPS)

by Adam Zalewski, Iana Andreieva, Justyna Wiśniowska, Beata Tarnacka and Grażyna Gromadzka

Int. J. Mol. Sci. 2025, 26(6), 2514; https://doi.org/10.3390/ijms26062514 - 11 Mar 2025

Viewed by 688

Abstract

Complex regional pain syndrome (CRPS) is an idiopathic, highly debilitating chronic disorder with persistent regional pain accompanied by a combination of sensory, motor, and autonomic abnormalities. It is not only difficult to treat but also difficult to study. This scoping review aimed to identify the key clinical and molecular challenges encountered in CRPS research and to examine the assessment tools currently employed. A comprehensive search was conducted across PubMed/Medline, Science Direct, Scopus, Wiley Online Library, and Google Scholar using a combination of free text and MeSH terms related to CRPS, clinical and molecular aspects, neuroinflammation, biomarkers, and research challenges. We analyzed 55 original clinical research papers on CRPS and 17 studies of immunological/biochemical/molecular aspects of CRPS. A significant degree of heterogeneity was observed in the methodologies employed across the reviewed studies. The most frequently reported challenges included difficulties in participant recruitment and controlling confounding factors (reported in 62% of studies), such as the heterogeneity of the patient population, the influence of pain coping strategies and psychological factors, and the impact of sociocultural factors (reported in 62% of studies). Research into diagnostic and prognostic markers for CRPS also faces numerous challenges. Recruiting participants is difficult due to the rarity of the condition, resulting in small sample sizes for studies. In vitro models often fail to replicate the complexity of in vivo inflammation, limiting their applicability. Findings from early CRPS stages may not generalize to chronic CRPS because of differing pathophysiological mechanisms and symptom profiles. Additional obstacles include the disorder’s heterogeneity, difficulties in controlling confounding factors, variability in treatment approaches, and the lack of standardized tools and baseline comparisons. These issues hinder the development of reliable biomarkers and evidence-based treatments. Due to these difficulties, the exact cause of CRPS is still not fully understood, making it difficult to develop effective, specific treatments and conduct targeted research. Full article

(This article belongs to the Special Issue Chronic Pain: Diagnosis, Pathophysiological Mechanisms and Treatment)

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