Chronic Pain Disease Research Articles

Development of a patient decision aid for people with chronic low back pain and degenerative disc disease considering lumbar fusion: A mixed-methods study.

To develop and user-test a patient decision aid providing evidence-based information for people with chronic low back pain (LBP) and degenerative disc disease considering lumbar fusion. Convergent parallel mixed methods study. A prototype patient decision aid was developed, guided by the International Patient Decision Aid Standards (IPDAS) criteria, a multidisciplinary steering committee, and insights from previous studies. Participants were recruited via social media and the authors' collaborative networks to refine and evaluate the decision aid. Individuals who underwent lumbar fusion for chronic LBP and health professionals who manage these patients were purposively sampled. Semi-structured interviews and questionnaires were used to gather feedback and assess the decision aid's acceptability, usability, and preparedness for decision-making. Framework analysis was used for interview data and descriptive analysis for questionnaires. Sixteen clinicians (5 physiotherapists, 2 rheumatologists, 2 surgeons, 7 general practitioners) and seven patients participated, most rating the prototype's acceptability as 'excellent' or 'good'. Usability (mean [SD], health professionals: 78 [16], patients: 72 [8]) and preparedness for decision-making (health professionals: 73 [14], patients: 72 [10]) also scored highly. However, some viewed the prototype as biased against lumbar fusion, and suggestions to include more personalised information were made. This study showed that our prototype patient decision aid is acceptable, useful, and prepares patients to make informed decisions about spinal fusion for chronic LBP and degenerative disc disease. Future studies will assess the clinical impact of our decision aid and its optimal distribution timing.

Cannabidiol induces autophagy via CB1 receptor and reduces α-synuclein cytosolic levels.

Numerous studies have explored the role of cannabinoids in neurological conditions, chronic pain and neurodegenerative diseases. Restoring autophagy has been proposed as a potential target for the treatment of neurodegenerative diseases. In our study, we used a neuroblastoma cell line that overexpresses wild-type α-synuclein to investigate the effects of cannabidiol on autophagy modulation and reduction in the level of cytosolic α-synuclein. Our results demonstrated that cannabidiol enhances the accumulation of LC3-II- and GFP-LC3-positive vesicles, which indicates an increase in autophagic flux. In addition, cannabidiol-treated cells showed a reduction in cytosolic α-synuclein levels. These effects were inhibited when the cells were treated with a CB1 receptor-selective antagonist, which indicates that the biological effects of cannabidiol are mediated via its interaction with CB1 receptor. Additionally, we also observed that cannabinoid compounds induce autophagy and α-synuclein degradation after they interact with the CB1 receptor. In summary, our data suggest that cannabidiol induces autophagy and reduces cytosolic α-synuclein levels. These biological effects are mediated preferentially through the interaction of cannabidiol with CB1 receptors, and therefore, cannabinoid compounds that act selectively on this receptor could represent a new approach for autophagy modulation and degradation of protein aggregates.

Impact of Formulation Variables on Meloxicam spanlastics Preparation

Spanlastic is a modern drug delivery that combines vesicular and nanoparticulate characteristics with numerous advantages over topical applied conventional vesicular systems in terms of stablility, penetration flexibility, and targeting. Meloxicam (MX) is a potent non-steroid anti-inflammatory drug that is frequently utilized for the short- and long-term treatment of chronic pain and inflammatory diseases including rheumatoid arthritis. However, the oral administration of MX often includes several adverse effects, including gastrointestinal disturbances and ulceration. Thus, the aim is a preparation of proper formula for MX-loaded spanlastics via studying the formulation variables that may affect their properties using the ethanol injection method. Variables include; span®60: edge activator ratio, the type of edge activators, the amount of MX, and the type of organic phase solvent were studied for their impact on particle size, polydispersity index, and entrapment efficiency. The formula that was selected showed sustained release for six hours, entrapment efficiency of 70.66±1.15%, zeta potential (-4.51), and particles that were 495±9.9 nm in size. Overall, the results indicated that spanlastics had the potential carrier for medicine delivery systems.

The Effect of Intravascular Laser Irradiation of Blood on Serum Biomarkers and Clinical Outcome in Knee Osteoarthritis Patients: A Double-Blind Randomized Control Trial.

Knee osteoarthritis (OA) is a prevalent degenerative joint disease globally, causing pain, stiffness, and disability. Intravascular laser irradiation of blood (ILIB) has been used for chronic pain and musculoskeletal disease. However, evidence on the clinical benefits and serum biomarkers post-ILIB therapy in knee OA is insufficient. We designed a double-blind randomized controlled trial to evaluate the clinical and biological outcomes of ILIB therapy for knee OA. Seventeen patients with knee OA were randomly assigned to the ILIB and control groups. The outcomes included the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Scale, visual analog scale, and biomarker analysis of interleukin (IL)-6, IL-13, IL-1β, epidermal growth factor, macrophage inflammatory protein-1β, and eotaxin. The measurements were performed at baseline and three days, one month, and three months post-intervention. The ILIB group showed a significant improvement in the WOMAC-pain score at one month of follow-up than the control group. IL-1β levels reduced significantly on day three, one month, and three months, and IL-13 levels reduced on day three and three months during follow-up in the ILIB group. ILIB therapy reduced knee OA pain for one month and significantly reduced serum IL-1β and IL-13 levels, suggesting potential for pain management.

Effectiveness and Safety of Gabapentin versus Pregabalin in the Treatment of Postherpetic Neuralgia: A Retrospective Cohort Study.

Aims/Background Postherpetic neuralgia (PHN) is a common chronic pain disease that persists after the rash (clusters of clear blisters on the surface of the skin) has healed, adversely affecting the quality of life of affected patients. Gabapentin (GPT) and pregabalin (PGB) are two commonly used drugs for the treatment of PHN, but there have been broad concerns regarding their efficacy and safety. Thus, this retrospective cohort study was conducted to investigate the effectiveness and safety of GPT versus PGB in the treatment of PHN. Methods A total of 150 patients with PHN receiving routine antiviral and neurotrophic therapies, admitted between January 2022 and November 2023, were selected. 71 patients who were treated with GPT were included in the control group, while the remaining 79 patients who were given PGB were categorized in the observation group. Information on clinical effectiveness, safety (xerostomia, drowsiness, blurred vision, ataxia, and dizziness), analgesic effect (Visual Analogue Scale [VAS] and time to pain relief), sleep quality (Sleep Quality Scale [SQS] and Pittsburgh Sleep Quality Index [PSQI]), and adverse emotions (Self-rating Anxiety/Depression Scale [SAS/SDS]) was collected for analysis. Results Compared to the control group, the observation group exhibited significantly higher clinical effectiveness of PGB in the treatment of PHN (p < 0.05). In other aspects, the overall incidence of adverse events such as xerostomia, drowsiness, blurred vision, ataxia, and dizziness (p > 0.05) was equivalent in these two groups. In addition, significantly lower VAS, SQS, PSQI, SAS, and SDS scores were observed in the observation group after treatment, compared with the control group (p < 0.05). The observation group showed evidently shorter time to pain relief than the other group (p < 0.05). Conclusion PGB is an effective and safe medication for the treatment of PHN, by improving the analgesic effect and sleep quality, and alleviating negative emotions.

Altered blood and keratinocyte microRNA/transfer RNA fragment profiles related to fibromyalgia syndrome and its severity.

Fibromyalgia syndrome (FMS) is a debilitating widespread chronic pain condition of unclear pathophysiology. We studied small noncoding RNAs as potential classifiers and mediators of FMS. Blood and keratinocyte microRNAs (miRs) and transfer RNA fragments (tRFs) were profiled by small RNA-sequencing within a comprehensively phenotyped female cohort of 53 patients with FMS vs 34 healthy controls (hCOs) and 15 patients with major depression and chronic physical pain (disease controls). Small RNAs were quantified via RNA-sequencing and candidates validated via qRT-PCR. MicroRNAs and tRFs were tested for association with FMS symptoms and their potential regulatory roles. miR and tRF profiles were altered in FMS compared to hCO in whole blood (n = 69; n = 22) and keratinocytes (n = 41; n = 55). Receiver operating characteristic analysis of blood miR candidates hsa-miR-148a-3p and hsa-miR-182-5p, and tRF candidate tRF-21-WB8647O5D levels separated FMS from hCO. In blood, hsa-miR-182-5p and hsa-miR-576-5p upregulation was validated via qRT-PCR, showing even higher expression in disease control, while TRF-20-40KK5Y93 was selectively increased in FMS. MicroRNAs in blood and keratinocytes were associated with how widespread pain manifested in patients. Keratinocyte tRFs correlated with loss of skin innervation. In blood, altered small RNAs were linked to immune and RNA processes, whereas in keratinocytes, adhesion and epithelial functions were targeted. Modulated tRFs shared sequence motifs in patients with FMS, which may promote concerted pathway regulation. Our findings show miRs/tRFs as key small RNAs dysregulation in FMS pathophysiology and open new perspectives for FMS diagnostics, symptom monitoring, and clinical management.

Endometriosis: Future Biological Perspectives for Diagnosis and Treatment.

Endometriosis is an oestrogen-dependent inflammatory disease affecting menstruating women, with varying levels of severity. Oestrogen dysregulation is responsible for chronic inflammation, angiogenesis, endometrial lesion development, progression, and infertility during menarche in afflicted women. The inflammatory mediators associated with this chronic painful disease have been established, with research also indicating the relationship between dysbiosis and disease manifestation. Endometriosis is also present with several painful comorbidities, including endometrial cancer, cardiovascular disease, and autoimmunity. The lack of specific and sensitive non-invasive diagnostic procedures, coupled with poor response to current therapeutic approaches, means that treatment needs remain unmet. Surgical procedures are performed to remove endometriosis ectopic lesions, for which the recurrence rate of disease is up to 50%, with certain patients exhibiting no alleviation of symptoms. This review aims to outline the aetiology of endometriosis, detailing novel diagnostic approaches and potential therapeutic approaches, namely advanced therapeutic medical products (ATMPs), including stem cell therapy and clustered regularly interspaced short palindromic repeats (CRISPR) gene editing. This timely review also provides novel insights into the important recent modalities which may be applied for the diagnosis and therapeutic response of endometriosis, including biomarkers, microfluidic platforms, and organoid systems. Undoubtedly, reliable, reproducible, sensitive, and specific models of endometriosis in humans are urgently needed to investigate and detail the aetiology of this debilitating disease.

EXPLORING THE FEASIBILITY OF PLATELET-RICH PLASMA INJECTIONS FOR INTERVERTEBRAL DISCOPATHY: A PILOT STUDY.

This longitudinal pilot study aimed to evaluate the feasibility, safety and potential benefits of Platelet-Rich Plasma injections into the lumbar intervertebral discs in patients with low back pain and degenerative intervertebral monodiscopathy, assessing potential efficacy on disability. Longitudinal pilot study. Six participants with chronic low back pain and lumbar degenerative intervertebral disc (monodiscopathy) disease underwent 1 Platelet-Rich Plasma injection, with a 1-year follow-up. Platelet-Rich Plasma injections were administered into the lumbar intervertebral disc, and outcomes were measured using the Roland Morris Disability Questionnaire, numeric rating scale for pain, Tampa scale for kinesiophobia and lumbar flexion range. Magnetic resonance imaging analysis assessed disc changes. No adverse events were reported. At the end of the 1-year follow-up, half of the patients showed significant improvements in disability scores at 1 year, while 3 of the 6 patients had no change. Magnetic resonance imaging revealed no significant disc changes. Platelet-Rich Plasma injections show promise for some patients with low back pain and degenerative intervertebral discopathy patients. However, caution is warranted due to study limitations, including small sample size and lack of a control group. Further research is needed to define Platelet-Rich Plasma therapy protocols.

Health and socioeconomic well-being of women with endometriosis and provoked vestibulodynia: Longitudinal insights from Swedish registry data.

Endometriosis and provoked vestibulodynia (PVD) are prevalent pain conditions among women of reproductive age, significantly impacting their quality of life and psychological well-being. However, comprehensive evidence regarding the lifelong health and socioeconomic outcomes for these individuals remains scarce. Additionally, many prior studies rely on limited and sometimes unrepresentative samples. This study aims to inform on the long-term consequences of these disorders by examining health, fertility, and employment outcomes in a cohort of women diagnosed with endometriosis and/or PVD, tracing their experiences from childhood to their 40s. Leveraging nationwide administrative data from Sweden and employing a matched case-control design, we investigate both similarities and differences between women with these diagnoses and those without. Our findings indicate that women diagnosed with endometriosis and/or PVD demonstrate elevated healthcare utilization patterns, commencing in their early teenage years and progressively increasing over time. Notably, disparities in labor market outcomes emerge in their 20s, showcasing lower labor earnings and a rise in sickness benefit receipt. Moreover, our results show a higher likelihood among these women to experience mental health disorders and concurrent chronic pain diseases, as well as infertility. While the association between endometriosis and infertility is well-documented, this study offers novel insights into a potential similar link between PVD and infertility. Our study informs healthcare professionals and policymakers about the considerable burden of compromised health, adverse psychosocial well-being, and reduced productivity in the labor market faced by young women with these common pain conditions. These findings underscore the urgency of addressing the multifaceted challenges encountered by individuals diagnosed with endometriosis and PVD across their lifespan.

Magnesium hexacyanoferrate nanocatalysts alleviates fibromyalgia syndrome by reversing cellular ferroptosis

Fibromyalgia (FM), the most common causes of chronic musculoskeletal pain, is a complex syndrome with an indefinite etiology. Ferroptosis is a new type of cell death characterized by iron-dependent lipid peroxidation, affecting many chronic pain diseases. Here, we confirmed the role of ferroptosis in FM using a mouse model of reserpine induction. Then, we developed polyvinylpyrrolidone-assembled magnesium hexacyanoferrate nanocatalysts (MgHCF NCs) as a new type of ferroptosis inhibitor, for its efficacy in ferrous ions capture and antioxidation. Excellent in vivo FM-alleviation effect from MgHCF NCs was demonstrated. The FM-protective and antiferroptotic efficacy of MgHCF NCs at the transcriptional level were explored by whole-transcriptome analysis. Meanwhile, the remarkable antiferroptotic effect of MgHCF NCs was further validated in vitro ferroptosis-inducer experiments, which was firmly associated with the efficacy of MgHCF NCs on reducing oxidative stress, mitochondrial protection and correcting disordered polyunsaturated fatty acids (PUFAs) metabolism. The excellent antiferroptotic effect and biocompatibility render MgHCF NCs to be highly promising and clinically transformable agents for FM treatment.

Is a Low Dosage of Medical Cannabis Effective for Treating Pain Related to Fibromyalgia? A Pilot Study and Systematic Review.

Background and Objectives: Fibromyalgia is a multifaceted and frequently misunderstood chronic pain disease marked by widespread musculoskeletal pain and cognitive/somatic dysfunction. This trial aims to contribute to the existing knowledge on treating fibromyalgia (FM) with medical cannabis (Cannabis sativa L.) and explore a safer and more effective cannabis administration method. The goal is to provide evidence-based findings that can guide alternative treatment options for FM patients by assessing a pilot study. Materials and Methods: The trial was performed at the pain therapy unit of the San Carlo Hospital (Potenza, Italy) by administrating to 30 FM patients 100 mg/day of Bedrocan® (Bedrocan International, Veendam, The Netherlands) as a decoction. The Numerical Rating Scale (NRS) and SF-12 short-form health questionnaire were used to evaluate pain intensity and the quality of life at the beginning of the study and the 6th-month follow-up. A systematic review of all clinical studies investigating the use of cannabis to reduce FM was also undertaken to place this study in the context of the existing evidence base. Results: Pain intensity evaluated with the NRS lowered from a median of 8 [95% CI 7.66-8.54] at a baseline to a median of 4 (95% CI 3.28-4.79) after 6 months of follow-up (p-value < 0.001; t-test). Similarly, significant physical and mental state improvement, evaluated with the SF-12 questionnaire, was found in 96.67% and 82.33% of patients, respectively (95% CI 44.11-51.13 for the physical state, and 53.48-58.69 for mental state assessed after the 6th-month follow-up; p-value < 0.001; t-test). The systematic analysis of the literature identified 10 clinical trials concerning the treatment of fibromyalgia with cannabis. Conclusions: Considering results from the present pilot study and systematic review, it is possible to assume that medical cannabis may be considered an alternative therapy for FM patients who do not respond to conventional pharmacological therapy.

Harnessing the ocean’s pharmacy: marine bioactive compounds as next-generation therapeutics

The ocean’s vast and diverse ecosystem offers a rich reservoir of bioactive compounds with immense clinical potential. Marine organisms produce structurally unique and biologically active compounds, leading to breakthroughs in therapeutic development. Notable examples include anticancer agents like trabectedin and cytarabine, and the analgesic ziconotide. Marine compounds also exhibit potent antimicrobial and antiviral properties, addressing critical challenges like antibiotic resistance and emerging viral infections. Despite the promise, challenges such as sustainable harvesting and complex extraction processes persist. Advances in synthetic biology and metabolic engineering provide solutions for sustainable production, ensuring a stable supply of these valuable compounds. The integration of marine bioactives into modern medicine could revolutionize treatments for cancer, chronic pain, and infectious diseases, underscoring the need for continued investment in marine bioprospecting and biotechnological innovation.

Preparation, Characterization, and Skin Permeation Evaluation of Naproxen Microemulsions for Transdermal Delivery

: Microemulsions (MEs) are considered for preparing drug delivery carriers, especially transdermal vehicles. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage chronic and acute pain and inflammatory diseases. However, NSAIDs have drawbacks such as gastrointestinal tract disorders and poor pharmacokinetic properties for oral administration. To address these issues, we evaluated the potential of ME as a transdermal system for locally delivering naproxen (NPX) as an NSAIDs model (NPX-MEs). Phase diagrams were constructed for MEs composed of tween 80, span 80, and propylene glycol (PG) as surfactant (S)/cosurfactant (CS), transcutol® P (TRC-P), and LabrafacTM PG as oil. The final concentration of NPX in MEs was 1% (w/v). The MEs were analyzed for particle size, refractive index, and viscosity. In vitro permeability studies of NPX-MEs were conducted using Franz diffusion cells on rat skin samples. Additionally, the effects of Eucalyptus oil (EU oil), oleic acid (OLA), and TRC-P as enhancers on the skin permeation of NPX were investigated. The particle size and viscosity values of the NPX-MEs ranged from 7.05 ± 0.03 to 79.56 ± 0.58 nm and 222.4 ± 0.87 to 681.13 ± 1.97, respectively. The optimal formulation, ME-3, consisted of 20% oil, 10% water, and 70% S/C phases. The skin permeation rates of NPX from ME-3 were higher than those of other formulations (Dapp = 1.36 ± 0.616, ERD=527.989 ± 313.627) with a lower lag time. Additionally, OLA-treated skin showed the highest transdermal permeation rate (ERD = 75.55 ± 23.532). Based on these results, the formulated NPX-ME may be a desirable carrier for transdermal delivery compared to traditional formulations, potentially reducing side effects and improving the therapeutic efficacy of NPX.

Interferon-gamma signaling promotes cartilage regeneration after injury

Osteoarthritis is a common chronic disease and major cause of disability and chronic pain in ageing populations. In this pathology, the entire joint is involved, and the regeneration of articular cartilage still remains one of the main challenges. Here, we investigated the molecular mechanisms underlying cartilage regeneration in young mice using a full-thickness cartilage injury (FTCI) model. FTCI-induced cartilage defects were created in the femoral trochlea of young and adult C57BL/6 mice. To identify key molecules and pathways involved in the early response to cartilage injury, we performed RNA sequencing (RNA-seq) analysis of cartilage RNA at 3 days after injury. Young mice showed superior cartilage regeneration compared to adult mice after cartilage injury. RNA-seq analysis revealed significant upregulation of genes associated with the immune response, particularly in the IFN-γ signaling pathway and qRT-PCR analysis showed macrophage polarization in the early phase of cartilage regeneration (3 days) in young mice after injury, which might promote the removal of damaged or necrotic cells and initiate cartilage regeneration in response to injury. IFN-γR1- and IFN-γ-deficient mice exhibited impaired cartilage regeneration following cartilage injury. DMM-induced and spontaneous OA phenotypes were exacerbated in IFN-γR1−/− mice than in wild-type mice. Our data support the hypothesis that IFN-γ signaling is necessary for cartilage regeneration, as well as for the amelioration of post-traumatic and age-induced OA.

ORAL OPIOID ANALGESICS VS SPINAL STEROID INJECTIONS IN THE TREATMENT OF LOW BACK PAIN: A COMPREHENSIVE SYSTEMATIC REVIEW

Introduction: Low back pain (LBP) affects a significant portion of the population worldwide, with distinct treatment needs for acute and chronic cases. Despite widespread opioid use, evidence for their efficacy in LBP remains uncertain, highlighting the need for alternative interventions. Minimally invasive procedures like epidural steroid injections offer potential relief for conditions like lumbar disc herniation, but their effectiveness is debated. To address these complexities, we conducted a comprehensive review encompassing various treatment modalities beyond medication, aiming to optimize outcomes and improve quality of life for individuals with LBP. Method: The researchers in this study followed the 2020 Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines to ensure that their work met the required standards. This was done to ensure the precision and reliability of the conclusions derived from the research. Result: Our search produced 13 results. After looking at the titles and summaries, we found 8 papers that fit our criteria. At first, we excluded several articles because they were written in review style and case reports. But after reading the full papers carefully, we included four papers in our final analysis. These papers included retrospective analysis, a randomized, double blind, placebo controlled cross-over study, noninterventional, retrospective 12-week study using anonymized clinical practice data from the German Pain eRegistry, and a retrospective analysis of anonymized, propensity score–matched data. Conclusion: Favorable post-injection outcomes suggest the blind method for caudal epidural injections is safe and effective, suitable for patients not eligible for surgery or unresponsive to conservative treatments. Interlaminar epidural steroid injections effectively reduce VAS and ODI scores in patients with chronic low back pain and multi-level disc disease, but further research is needed to standardize administration protocols and optimize treatment outcomes, including addressing BMI's impact. The analgesic efficacy of periradicular meloxicam injections for acute/subacute low back pain, indicating a potential new treatment option, while real-world data suggest NBX oromucosal spray may be superior to typical oral LAO analgesics for severe peripheral NBP, pending confirmation in large RCTs.

Mediating effect of depressive symptoms on the relationship of chronic pain and cardiovascular diseases among Chinese population: Evidence from the CHARLS

ObjectiveFew studies have examined the direct or indirect effect of chronic pain on cardiovascular diseases (CVD) within Chinese population. The objective aimed to investigate the mediating role of depressive symptoms between chronic pain and CVD. Methods6522 participants from China Health and Retirement Longitudinal Study were included in this retrospective cohort study. The main endpoint was the occurrence of CVD. Weighted multivariate logistic regression was used to assess the association between chronic pain and depressive symptoms. Distribution-of-product method was employed to examine the mediation effect of depressive symptoms. Subgroup analyses were performed. Results219 developed CVD at the end of follow-up period. After adjusting all confounding variables, chronic pain was associated with increased risk of depressive symptoms in total population [odds ratio (OR) = 3.85, 95%confidence interval (CI): 3.35–4.42]. Among total population, there was a positive association of chronic pain and CVD [risk ratio (RR)a = 2.00, 95% CI: 1.33–3.00] (total effect). After further adjusting depressive symptoms, the association between chronic pain and CVD was significant (RRb = 1.67, 95% CI: 1.16–2.41) (direct effect). According to the distribution-of-product test, we observed a mediating effect of depressive symptoms on the relationship between chronic pain and CVD with the percentage of mediation of 32.8%. The mediating effect of depression was observed in individuals of aged45–65 years old, female participants, participants who never drinking and not have hypertension. ConclusionChronic pain was positively associated with CVD for Chinese population, and depressive symptoms was considered to mediate the association between chronic pain and CVD.

Model-Based Assessment of the Liver Safety Profile of Acetaminophen to Support its Combination Use with Topical Diclofenac in Mild-to-Moderate Osteoarthritis Pain.

The use of combination therapy of oral acetaminophen and topical diclofenac, having complementary mechanisms of action, is an attractive strategy to enhance the analgesic response in osteoarthritis (OA) pain. While topical diclofenac is considered as well tolerated due to its low systemic exposure, concerns of liver toxicity with acetaminophen at standard analgesic doses remain. Thus, this study aimed to assess the liver safety profile of acetaminophen, particularly in OA management, using a model-based meta-analysis (MBMA). A literature review was conducted using the MEDLINE database to identify randomized clinical trials (RCTs) reporting liver toxicity on acetaminophen use. An MBMA was implemented to assess the deviation from the upper limit of normal (ULN) of alanine aminotransferase or aspartate aminotransferase, namely > 0-1 × ULN, > 1.5-2 × ULN, and > 3 × ULN representing mild, moderate, and severe risk of liver abnormality, respectively. A total of 15 RCTs were included in the MBMA, encompassing over 4800 subjects and exposure to acetaminophen ranging from 2 to 26weeks. Of the 15 included studies, eight involved patients with OA pain, four involved healthy subjects and three were in patients with conditions such as asthma, glaucoma, chronic pain, and cardiovascular disease. Acetaminophen 1500-4000mg/day was found to exhibit 23% (95% confidence interval (CI): 17.74-29.20), 1.35% (95% CI: 0.17-2.51) and 0.01% (95% CI: 0.00-0.32) increased risk for mild, moderate, and severe liver injury, respectively, versus placebo. Moreover, at therapeutic doses, no correlation was identified between acetaminophen intake and liver abnormality risk. Overall, our analysis shows that short-term (~ 8-16weeks) acetaminophen use at therapeutically recommended doses is associated with a low risk of clinically relevant changes in liver enzymes. Given the good tolerability of topical diclofenac, the findings support the safety of the combination of acetaminophen and topical diclofenac, at least over the short term, as treatment for mild-to-moderate OA pain.

Dyslipidemia Is Positively Associated with Chronic Low Back Pain in Korean Women: Korean National Health and Nutrition Examination Survey 2010-2012.

This study aimed to evaluate the association between chronic low back pain (CLBP) and chronic diseases, such as hypertension, diabetes, and dyslipidemia. This study was a retrospective analysis using data from the Korea National Health and Nutrition Examination Survey (KNHANES) between 2010-2012 and included women who answered a questionnaire in the KNHANES asking whether they had low back pain for ≥3 months. Participants were divided into non-CLBP and CLBP groups. For statistical analysis, the Student's t-test, chi-square test, Fisher's exact test, and logistic regression analysis were performed using SPSS. Of 5961 participants, the non-CLBP group comprised 4098 women and the CLBP group comprised 1863. Adjusted logistic regression model revealed that dyslipidemia was positively associated with CLBP (odds ratio, 1.32; 95% confidence interval, 1.140, 1.530; p < 0.001). However, hypertension and diabetes were not associated with CLBP. Our results suggest that proper treatment of dyslipidemia may contribute to lowering the risk of CLBP later in life.

Differential DNA methylation profiles of Alzheimer's disease-related genomic pathways in the blood of cognitively-intact individuals with and without high impact chronic pain

Background Chronic pain and Alzheimer's disease (AD) are prevalent in older age and their etiologies remain to be understoodand evidence supports potential associations between the two. Both high impact pain and AD have been previously associated with differences in the epigenome. Interactions with the epigenome may serve as a possible underlying mechanism linking high impact pain and AD. Objective To complete epigenetic canonical pathways analyses related to AD in individuals with and without high-impact knee pain. Methods This manuscript aimed to explore differences in DNA methylation patterns in genes and pathways associated with AD. Blood samples of cognitively intact, community-dwelling adults with high impact knee painmversus pain-free controls were compared on their DNA methylation levels of AD-related genes. Pathway enrichment analysis was performed on significantly different DNA Methylation probes by pain group. Results There were significant DNA methylation differences between the high impact versus the pain-free control groups in genes and pathways associated with AD (p &lt; 0.05). We found a total of 17,563 differentially methylated CpG probes, including 13,411 hypermethylated CpG probes and 4152 hypomethylated CpG probes. Further, pathway analysis revealed these differences were significantly associated with AD-related pathways associated with AD progression. Conclusions This study sample showed AD-related DNA methylation differences and associated potential canonical pathways in those with and without high impact knee pain. These results highlight the need to study overlapping epigenetic modifications underlying high impact pain and AD pathologies. Further studies, including gene expression, are needed to further explore the relationship between epigenetics, chronic pain, and AD.

Research progress of nociplastic pain in the clinical treatment of chronic pain diseases

Chronic pain is increasingly developing into a worldwide health problem. Due to the money and treatment required for care and rehabilitation, as well as the complexity of the various types of pain, chronic pain sufferers often bear a huge financial burden as well as a psychological one. According to statistics, 23% of chronic pain sufferers have suicidal thoughts. In 2017, the third category pain named "nociplastic pain" was proposed for the first time by the International Association for the Study of Pain (IASP) which is disparate with the first kind nociceptive pain and the second pain neuropathic. The physiological mechanisms behind this type of pain are not known. However, it is commonly thought to be associated with a hypersensitivity response in the central nervous system and can be resulted in chronic nociceptive pain, so nociplastic pain is able to occur by itself, and can combine with other pain. At the same time, this type of pain affects the central system and produces other derived symptoms. Examples include stimulation of the limbic system, including impaired processing of emotions by the amygdala, amplified pain perception, sleep disturbances, increased fatigue and sensitivity to external environmental stimuli. There are no very clear and obvious diagnostic criteria or methods, and clinical detection is difficult. Due to the many symptoms, patients usually undergo multiple tests, with high medical costs and a poor prognosis. Patients suffer both physical and psychological distress. The disease with its complexity characteristic leads the difficulty for doctors to diagnosis it plagues patients with the condition, while increasing the difficulty of medical diagnosis and the cost of medical treatment. This article synthesizes the existing developments in outcomes in nociplastic pain from introduction and classification to diagnosis and treatment, it discusses the existing research findings.