Frontiers in pain research (Lausanne, Switzerland)最新文献

Abdominal pain represents a frequent presenting symptom in emergency departments, with up to 20% of patient visits involving abdominal and/or flank pain. Recently published studies indicate that anterior cutaneous nerve entrapment syndrome (ACNES) is a more common cause of these symptoms than previously believed, with up to 2% of patients presenting to the emergency department at teaching hospitals being ultimately diagnosed with the condition. Importantly, ACNES is often misdiagnosed as another cause of abdominal pain. We present a 76-year-old patient whose a chief complaint was persistent abdominal pain localized to the right side of the umbilicus over a 6-week period, associated with a burning sensation of the skin. Following unremarkable laboratory, imaging, and endoscopy findings, the diagnosis of ACNES was confirmed with simple Carnett's sign. This is the first documented report to highlight that interventional treatment when combined with exogenous factors can contribute to the repair of nerve damage.

From an etiological perspective, the International Association for the Study of Pain (IASP) classifies pain into three categories: nociceptive pain (NcP), neuropathic pain (NeP), and nociplastic pain (NpP). In clinical practice, distinguishing between NpP and NeP can be particularly challenging. They share many clinical characteristics, including pain hypersensitivity and spontaneous pain. Currently, no evidence-based diagnostic method has been established for NpP, as defined by the IASP. Questionnaires had been developed before the IASP officially adopted NpP in 2017. Therefore, they cannot reliably distinguish between NpP and NeP. There is a previously unrecognized academic ambiguity arising from the coexistence of the unified concept of NeP including NpP and the separate concept of NeP excluding NpP. Moreover, NpP diagnosed using different criteria can coexist. There is currently no established guideline for either the pharmacological or the non-pharmacological treatment of NpP. The treatment of fibromyalgia, a typical NpP, closely resembles that of NeP. The theoretical concept of NpP has generated substantial uncertainty not only in pain research but also in clinical practice, particularly regarding diagnosis and treatment. To simplify diagnosis and treatment, resolve scholarly uncertainty, and improve the care of patients with pain, four provisional plans are proposed until an evidence-based method for diagnosing NpP has been established. (1) Integrate NpP into NeP and use the term NeP. (2) Classify NpP as a subcategory of NeP and use the term NeP. (3) Integrate NpP into NeP and use the term new NeP (nNeP). (4) Classify NpP as a subcategory of NeP and use the term nNeP. The recommended plan is (1). It is hoped that these four proposals will serve as constructive contributions toward advancing both the conceptual understanding of pain and its treatment.

Introduction: Concerns regarding the side effects of pharmacotherapy in the management of joint pain have led to increased interest in dietary supplements. Astragalus membranaceus root extract (AME) has been proposed as an alternative approach to relieving knee joint pain. The present study evaluated the efficacy and safety of a standardized AME in patients with functional knee joint pain.

Methods: A double-blind, randomized controlled trial was conducted with 90 adults (18-60 years of age) from Rajalakshmi Hospital and Research Center, Karnataka, India. Participants were randomly assigned to receive either 480 mg of AME (n = 45) or placebo (n = 45) for 28 days. The primary outcome was knee pain reduction, which was assessed using a visual analog scale (VAS) after a 6-min walk test. Secondary outcomes included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Stair Climb Test (SCT), knee range of motion (ROM), and treatment compliance, evaluated at baseline and at follow-up on days 5, 14, and 28. Patient satisfaction and safety were also assessed.

Results: The AME group exhibited a significant 30% reduction in knee pain (p < 0.0001), with mean VAS scores dropping from 6.7 ± 0.5 to 1.2 ± 0.6. Significant improvements were observed in the WOMAC, SCT score, and ROM (p < 0.0001). Patient satisfaction was higher in the active-treatment group, and no serious adverse events were reported.

Discussion: AME was a safe and effective alternative for the management of knee joint pain and merits further longer-term investigation.

Clinical trial registration: https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=OTE3MTU=&Enc=&userName=, identifier CTRI/2023/09/057317.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect in patients undergoing chemotherapy. Many commonly used chemotherapeutic agents simultaneously induce neurotoxicity and modulate the immune system. Emerging evidence highlights a critical role of the innate immune system in the development of various neuropathic pain conditions. As a natural immune defense mechanism formed during phylogenetic evolution, innate immunity elicits a robust response during CIPN pathogenesis. This review summarizes the roles of the innate immune system-including the skin barrier, innate immune cells, and innate immune molecules-in the context of CIPN.

Rheumatoid arthritis (RA) pain is one of the most common forms of chronic pain in clinic. A large number of RA-related literature has been reported. At present, although some analgesic measures are used in clinic, pain management after drug treatment remains suboptimal in real-world settings, and clinically meaningful pain after treatment is still reported. RA pain is a complex pathological process that involves inflammatory response, neuroimmune interaction, peripheral and central nerve sensitization, autoantibodies, structural damage, and other dimensions. Although inflammatory reaction is the most common cause of RA-induced pain, neuroimmune interaction is the key and core of RA pain, and autoantibodies are one of the significant characteristics of RA, which can directly or indirectly lead to pain. In addition, joint structural damage is the final pathological stage and a serious consequence in the late stage of RA. This article aims to summarize the mechanisms of RA pain, which is helpful to further clarify the diagnosis and provide targeted treatment.

Objective: To investigate the clinical efficacy of medical ozone injections into the intervertebral disc on relieving lumbosacral pain. through a systematic review and meta-analysis.

Methods: A comprehensive literature search was conducted in PubMed, Cochrane Library, and Web of Science for English-language randomized controlled trials (RCTs) published between January 2010 and January 2025. The study was registered in the PROSPERO International Prospective Register of Systematic Reviews (CRD42023417837). Primary clinical outcomes included pain reduction assessed by Visual Analog Scale (VAS) scores and functional improvement assessed by the Oswestry Disability Index (ODI). Statistical analyses were performed using Review Manager 5.4.

Results: Eight RCTs involving 1,744 patients were included. Among them, 903 people received medical ozone injections into the intervertebral discs, while 841 people received other forms of treatment. Meta-analysis showed that medical ozone injections significantly reduced VAS scores (mean difference = -2.13, 95% CI: -2.33 to -1.93, p < 0.05) and improved ODI scores (mean difference = -0.79, 95% CI: -0.95 to -0.63, p < 0.05), indicating superior short-term efficacy compared to conventional treatments.

Conclusions: Ozone injection into the intervertebral discs is an effective non-invasive treatment method, which can effectively relieve pain in the lumbar and sacral regions, especially showing significant effects in the short term. However, Further long-term studies are warranted to evaluate the durability of clinical benefits.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42023417837, PROSPERO CRD42023417837.

Myofascial pain syndrome (MPS) is a leading cause of chronic musculoskeletal pain, yet its mechanisms remain debated. Traditional models emphasized muscle contracture or central sensitization, but growing evidence highlights fascia as a biologically active, pain-relevant tissue. Pathological alterations such as densification, fibrosis, and inflammation may generate nociceptive input and sustain persistent symptoms. To explore this perspective, we conducted a conceptual narrative review of studies published between 2000 and 2025 in PubMed, Embase, Scopus, and Google Scholar. Eligible publications included anatomical, histological, imaging, biomechanical, and clinical investigations, and evidence was synthesized narratively into an integrative model of mechanisms. This mini-review followed the SANRA guidelines for narrative reviews. The literature demonstrates that fascia is richly innervated by nociceptors and sympathetic fibers and undergoes pathological changes in patients with MPS. Imaging and histological studies confirm fibrosis, densification, and inflammatory activity in symptomatic fascia. Mechanistic pathways linking fascia to pain include impaired sliding, abnormal mechanotransduction, and neuroinflammatory sensitization. Clinically, patients exhibit tenderness on fascial palpation, imaging evidence of stiffness, and symptomatic improvement after fascia-focused therapies. These findings suggest that fascia functions as a key peripheral driver in MPS. This concept was first formalized as the 'integrated hypothesis' by Simons in 2004. Integrating fascia into existing frameworks reconciles muscle-based and central sensitization models, providing a plausible substrate that initiates nociceptive signaling, perpetuates central adaptations, and interacts with psychosocial influences. This integrative model may explain the heterogeneity of MPS and supports multimodal treatment strategies that combine fascial therapies with central and psychosocial interventions. Although current evidence remains preliminary and heterogeneous, recognizing fascia as a central but interconnected contributor to MPS offers a more comprehensive understanding of this syndrome and a clinically relevant framework for future diagnostic and therapeutic innovation in pain medicine.

The complex relationship between pain and sleep has received increasing attention for its therapeutic potential. Over half of chronic pain patients suffer from sleep disorders, and poor sleep is a strong predictor for pain in clinical populations. Understanding the bidirectional relationship between pain and sleep is crucial for developing improved clinical treatment strategies. This review provides (1) a primer on preclinical methods used to measure sleep behaviors, (2) an overview of neural circuits at the intersection of pain and sleep, and (3) considerations for future pain and sleep investigations and treatment strategies.

Background: Toothache of cardiac origin is a rare but significant form of referred pain originating from cardiac pathology such as angina pectoris. Although jaw and throat discomfort are known referred pain sites, toothache alone is an uncommon presentation. Misdiagnosis often leads to unnecessary dental interventions and delays in appropriate cardiac treatment, highlighting the need for greater awareness among both dentists and internists.

Case presentation: A 76-year-old woman presented with persistent pain in the gingiva around teeth #33 and #34, accompanied by sharp chest discomfort which would subside in about 5-6 min. Extensive dental examinations, including extractions, failed to resolve her symptoms. Initial cardiac evaluations-electrocardiogram, Holter monitoring, echocardiography, and chest computed tomography-were unremarkable. Consequently, she was diagnosed with atypical odontalgia and prescribed antidepressants, but these proved ineffective. However, over several months, the toothache worsened upon exertion, accompanied by chest pain unresponsive to standard analgesics. A specialized cardiac imaging center finally detected severe stenosis (90%-99%) of the left anterior descending artery and Right Coronary Artery, as well as a left ventricular thrombus. Coronary angiography confirmed unstable angina, and the patient underwent a Dor procedure to remove the thrombus alongside coronary artery bypass grafting. Following surgery, her toothache and chest pain completely resolved.

Conclusion: This case features a protracted course from symptom onset to definitive treatment. In older patients reporting persistent tooth or gingival pain with intermittent chest discomfort-especially when symptoms are exertional and dental findings are negative-clinicians should consider a cardiac origin and expedite cardiologic imaging to avert hazardous delays. Systematic accumulation of cases and cross-disciplinary research are essential to establish actionable diagnostic guidance and move beyond anecdotal evidence.

Introduction: Biological aging and sex interact to shape systemic metabolism, yet their role in chronic pain resolution remains unexplored. We hypothesized that metabolic resilience-the ability to flexibly switch fuel sources and maintain energy homeostasis-rules successful recovery from nerve injury in a sex-dependent manner during aging.

Methods: In 12-month-old male and female mice, corresponding to the perimenopausal phase in females and the onset of hormonal decline in both sexes, we induced sciatic nerve chronic constriction injury and performed multi-omics profiling during Wallerian degeneration, a phase known to trigger long-term neurobiological remodeling.

Results: Aging females exhibited early activation of fatty acid oxidation, increased resting energy expenditure, upregulation of mitochondrial redox enzymes and circulating progesterone and corticosterone. Proteomic and metabolomic analysis revealed pentose phosphate pathway enrichment and gluconeogenesis, supporting redox balance and metabolic flexibility. Conversely, males displayed persistent glycolytic reliance, long-chain acylcarnitine accumulation, suppression of adiponectin and PPARγ, indicating metabolic inflexibility. Longitudinal behavioral analysis revealed that aging females recovered earlier and more fully than aging males, reversing the pattern previously shown in our adult mouse study, where females developed persistent pain and males recovered rapidly.

Discussion: These patterns highlight a non-linear, sex-specific interaction between biological aging and injury response, where hormonal decline reprograms the metabolic trajectory and reshapes pain outcomes. Metabolic resilience governs sex-specific recovery following nerve injury by directing early systemic adaptations that precede and predict long-term pain trajectories. These results define mechanistically anchored, sex- and age-specific biomarkers, and propose preclinical targets for timely, personalized interventions in age-associated neuropathic pain.