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

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.

Objective: To investigate the trajectories of acute postsurgical pain (APSP) following total knee arthroplasty (TKA), its influencing factors, and its impact on knee function recovery at 3 months postoperatively.

Methods: A convenience sample of patients undergoing TKA at a tertiary hospital in Panzhihua City between June 2024 and February 2025 was recruited. Preoperatively (T0), baseline data including demographics, anxiety, depression, family care index, pain level, and pain catastrophizing were collected. Postoperative pain levels were assessed on days 1 (T1), 2 (T2), 3 (T3), and 5 (T4), while joint functional outcomes were evaluated at 3 months postoperatively (T5). Growth mixture modeling (GMM) was used to identify distinct APSP trajectory subgroups, logistic regression was used to analyze influencing factors, and multiple linear regression was used to examine the association between APSP trajectories and joint functional outcomes.

Results: Among 227 enrolled patients, two APSP trajectory subgroups were identified: a moderate-high persistent pain group (45.16%) and a moderate-low rapid relief group (54.84%). Logistic regression revealed that age, preoperative pain level, pain catastrophizing, and family care index significantly influenced APSP trajectories. APSP trajectory membership positively predicted 3-month knee joint functional outcomes.

Conclusion: TKA patients exhibit two distinct APSP trajectory patterns, which serve as significant predictors of joint functional outcomes. Clinicians should identify the persistent pain subgroup and implement enhanced multimodal analgesia to prevent chronic postsurgical pain and optimize rehabilitation outcomes.

The prevalence of acute pain has grown substantially over the past two decades, due primarily to more surgeries, an aging population, and the rapid growth in the prevalence of metabolic disease. Although opioids are often the only effective treatment for many types of acute pain, especially severe acute pain, their use, even over a short period of time, comes with substantial risks of dependence, misuse, and diversion. Moreover, a large fraction of the patients currently suffering from opioid use disorder and those dying from opioid overdoses had their first exposure as pain patients. Conversely, refraining from using opioids in cases where other treatment options are ineffective creates a different set of risks. This potential undertreatment of acute pain, especially severe acute pain, increases the risk of acute pain transitioning to chronic pain. The use of opioids to treat acute pain and the ineffective treatment of acute pain have important implications for population health and health care costs.

Background: Bone cancer pain is a common complication of advanced malignant tumors.Chemotherapeutic drugs, regardless of their origin or type, are often associated with various adverse effects such as gastrointestinal toxicity, immune suppression, and acquired drug resistance, which can compromise patients' quality of life and treatment compliance. Electroacupuncture, known for its safety and analgesic effects, has been increasingly studied in bone cancer pain but the underlying mechanism is not fully understood.

Objective: To explore the mechanism of electroacupuncture in rats with bone cancer pain.

Methods: Forty-eight SD rats were divided into four groups: blank control, sham electroacupuncture, electroacupuncture-1, and electroacupuncture-2, with 12 rats in each group. Except the control group, rats were inoculated with cancer cells in the left tibia to induce bone cancer pain. The electroacupuncture groups received interventions starting on the 6th day after modeling. Mechanical pain sensitivity (PWT) and thermal pain sensitivity (PWL) were assessed, and the expression of phosphorylated glycogen synthase kinase-3 (p-GSK-3) and glial fibrillary acidic protein (GFAP) in the spinal cord were analyzed. HE staining was used to observe tibial pathological changes.

Results: From the 6th day, PWT and PWL were significantly reduced in the control group compared to the sham group (P < 0.05). Electroacupuncture-1 significantly increased PWT and PWL compared to the sham group (P < 0.05), while no significant changes were observed in electroacupuncture-2 compared to the control. On day 12, spinal p-GSK-3 levels were significantly lower and GFAP levels significantly higher in the model and control groups compared to the electroacupuncture-1 group (P < 0.05). The electroacupuncture-2 group showed no significant changes. Inflammatory cytokines IL-1, IL-6, and TNF-α were significantly elevated in the model group compared to the control (P < 0.05), but significantly reduced in the electroacupuncture-1 group (P < 0.05). HE staining showed cancer cell infiltration and bone tissue damage in the sham and electroacupuncture groups.

Conclusion: Electroacupuncture significantly reduced the pain threshold in rats with bone cancer pain. This effect is likely due to the down-regulation of GSK-3 activity, inhibition of astrocyte activation, and reduction in inflammatory responses.

Background: While prior studies suggest an increased risk of stroke among individuals with migraine, particularly those with migraine with aura, data on how specific migraine characteristics and comorbidities influence this risk across diverse populations remain limited. The All of Us database provides a unique opportunity to address this gap given its large sample size and inclusion of historically underrepresented groups.

Methods: A cross-sectional case-control analysis using multivariable regression models accounting for vascular risk factors and comorbidities was performed to compare the risk of stroke between individuals with and without migraine, odds ratios (OR) using a 95% confidence interval (CI) were calculated.

Results: Within the All of Us database, 31,444 individuals received a migraine diagnosis [female = 25,374/81%, male = 5,391/17%, other = 679/2%; mean (std) age = 54.9 (15.6)] and 379,283 did not have a migraine diagnosis [female = 222,104/59%, male = 149,182/39%, other = 7,997/2%; mean (SD) age = 55.9 (17.2)]. The migraine group had a greater proportion of women (81% vs. 59%), a higher proportion of white individuals (61% vs. 55%) and fewer African American individuals (15% vs. 19%). Compared to the non-migraine group, individuals with migraine had higher rates of comorbidities, including depression (46% vs. 12%), diabetes (16% vs. 7%), tobacco use (36% vs. 15%), hyperlipidemia (52% vs. 24%), hypertension (54% vs. 26%), and atrial fibrillation (3% vs. 2%).A multivariable regression model adjusted for differences between group demographics and comorbidities found that compared to those without migraine, individuals with migraine had a higher risk of overall stroke [OR 1.97, 95% CI (1.88, 2.07)], ischemic stroke [OR 1.38, 95% CI (1.24, 1.53)] and hemorrhagic stroke [OR 1.75, 95% CI (1.60, 1.92)]. Individuals with chronic migraine had a higher risk of overall stroke compared to the non-migraine group [OR 2.56, 95% CI ( 2.32, 2.84)] and compared to episodic migraine [OR 1.90, 95% CI (1.81, 2.00)]. Those with migraine with aura had a higher risk of stroke compared to individuals with migraine without aura [OR 1.33, 95% CI (1.20, 1.48)].

Conclusions: Individuals with migraine, particularly those with chronic migraine had a higher risk of stroke compared to those without migraine and compared to individuals with episodic migraine. The risk of stroke was higher in those with migraine with aura compared to those with migraine without aura even after adjusting for vascular comorbidities. Our analysis, using data from the All of Us database, confirms previous findings and suggests that while vascular comorbidities are more prevalent in those with migraine, they do not fully account for the increased risk of stroke.