Joint pain is the hallmark symptom of osteoarthritis (OA) and the main reason for patients to seek medical assistance. OA pain greatly contributes to functional limitations of joints and reduced quality of life. Although several pain-relieving medications are available for OA treatment, the current intervention strategy for OA pain cannot provide satisfactory pain relief, and the chronic use of the drugs for pain management is often associated with significant side effects and toxicities. These observations suggest that the mechanisms of OA-related pain remain undefined. The current review mainly focuses on the characteristics and mechanisms of OA pain. We evaluate pathways associated with OA pain, such as nerve growth factor (NGF)/tropomyosin receptor kinase A (TrkA), calcitonin gene-related peptide (CGRP), C–C motif chemokine ligands 2 (CCL2)/chemokine receptor 2 (CCR2) and tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β), the NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome, and the Wnt/β-catenin signaling pathway. In addition, animal models currently used for OA pain studies and emerging preclinical studies are discussed. Understanding the multifactorial components contributing to OA pain could provide novel insights into the development of more specific and effective drugs for OA pain management.

Osteoarthritis Pain

Objective To evaluate the global burden of musculoskeletal (MSK) disorders, as well as the five common conditions, and their relevant risk factors from 1990 to 2019. Design Data from the Global Burden of Disease Study 2019 were used in this study. Setting and participants Individuals of all ages and genders from 204 countries and territories in 21 regions. Main outcome measures The outcomes were the numbers and age-standardised rates (ASRs) of incident cases, deaths and disability-adjusted life-years (DALYs) of MSK disorders. The average annual percent changes (AAPCs) in the ASRs were calculated using joinpoint regression analysis to estimate the trends. Results There were 322.75 million incident cases, 117.54 thousand deaths and 150.08 million DALYs of MSK disorders in 2019. The age-standardised incidence rate and age-standardised DALY rate in 2019 (incidence: AAPC=−0.32, 95% CI −0.34 to −0.31; DALYs: AAPC=−0.05, 95% CI −0.06 to −0.04) were lower than those in 1990. However, the age-standardised death rate showed a stable trend (AAPC 0.05, 95% CI −0.05 to 0.15) from 1990 to 2019. The peak age of onset and DALYs of MSK disorders was 50–54 years in 2019. The burden of MSK disorders in females was much higher than that in males (1.29 times more incident cases, 2.24 times more deaths and 1.45 times more DALYs in females than in males). A significant negative correlation was observed between the AAPCs in the ASRs and the Sociodemographic Index (SDI) score. Occupational risk exhibited the highest contribution to MSK disorders, and tobacco use and high body mass index were also major risk factors. Conclusions This study demonstrates that the burden of MSK disorders tends to be lower in high-SDI regions than in lower-SDI regions. Strengthening the effectiveness of preventive measures against occupational risks may reduce the burden of MSK disorders.

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Global burden of musculoskeletal disorders and attributable factors in 204 countries and territories: a secondary analysis of the Global Burden of Disease 2019 study

Intervertebral disc (IVD) degeneration (IVDD) that greatly affected by regional biomechanical environment is a major cause of low back pain. Injectable hydrogels have been commonly studied for treatment of IVDD due to their capability of mimicking extracellular matrix structure to support cellular behavior and clinical prospects in minimally invasive treatment. However, most hydrogels suffer from complicated chemistry, potential uncertainty and toxicity from in-situ gelation, and mismatch with IVD mechanical environment that limit their therapeutic effects or clinical translation in IVDD or intervertebral disc defect repair. For IVD lesion repair, the study aims to develop a novel hydrogel with shear-thinning enabled injectability, high bio-safety, and mechanical properties adaptable to the IVD environment, using a simple chemistry and method. And therapeutic efficacy of the novel hydrogel in the treatment of IVDD or intervertebral disc defect will be revealed.A glycerol cross-linked PVA gel (GPG) was synthesized based on multiple H-bonds formation between glycerol molecules and PVA chains. The rheological and mechanical properties were tested. The swelling ratio was measured. The micro-architecture was observed through scanning and transmission electron microscopes. Nucleus pulposus (NP) cells were cultured in GPG-coated plates or silicone chambers treated under hydrostatic or dynamic loading in vitro, and examined for proliferation, vitality, apoptosis, expression of catabolic and anabolic markers. GPG was injected in needle puncture (IDD) or NP discectomy (NPD) models in vivo, and examined through magnetic resonance imaging, micro-computed tomography scanning and histological staining.GPG had a highly porous structure consisting of interconnected pores. Meanwhile, the GPG had NP-like viscoelastic property, and was able to withstand the cyclic deformation while exhibiting a prominent energy-dissipating capability. In vitro cell tests demonstrated that, the hydrogel significantly down-regulated the expression of catabolic markers, maintained the level of anabolic markers, preserved cell proliferation and vitality, reduced apoptotic rate of NP cells under pathologically hydrostatic and dynamic loading environments compared to cells cultured on untreated plate or silicone chamber. In vivo animal studies revealed that injection of GPG efficiently maintained NP structural integrity, IVD height and relative water content in IDD models, and stimulated the fibrous repair in NPD models.This study showed that GPG, with high injectability, NP-like viscoelastic characteristics, good energy-dissipating properties and swelling capacities, preserved NP cells vitality against pathological loading, and had therapeutic effects on IVD repair in IDD and NPD models.Effective clinical strategy for treatment of intervertebral disc degeneration (IVDD) is still lacking. This study demonstrates that injection of a hydrogel with nucleus pulposus-matched viscoelastic property could remarkably prevent the IVDD progress. Prepared with simple chemistry and procedure, the cell/drug-free GPG with high bio-safety and shear-thinning enabled injectability bears great translational potential for the clinical treatment of IVDD via a minimally invasive approach. 

https://doi.org/10.1016/j.jot.2022.03.006

Injectable hydrogel with nucleus pulposus-matched viscoelastic property prevents intervertebral disc degeneration

Injectable and tissue adhesive EGCG-laden hyaluronic acid hydrogel depot for treating oxidative stress and inflammation.

Background This study describes the global epidemiology and trends associated with neck pain. Global Burden of Disease data collected between 1990 and 2019 were used to determine the global burden of neck pain in the general populations of 204 countries. Methods Global, regional, and national burdens of neck pain determined by prevalence, incidence, and years lived with a disability (YLD) from 1990 to 2019 were comprehensively analyzed according to age, gender, and socio-demographic index using the Global Burden of Disease Study 1990 and 2019 data provided by the Institute for Health Metrics and Evaluation. Results Globally, in 2019, the age-standardized rates for prevalence, incidence, and YLD of neck pain per 100,000 population was 2,696.5 (95% uncertainty interval [UI], 2,177.0 to 3,375.2), 579.1 (95% UI, 457.9 to 729.6), and 267.4 (95% UI, 175.5 to 383.5) per 100,000 population, respectively. Overall, there was no significant difference in prevalence, incidence, or YLD of neck pain between 1990 and 2019. The highest age-standardized YLD of neck pain per 100,000 population in 2019 was observed in high-income North America (479.1, 95% UI 323.0 to 677.6), Southeast Asia (416.1, 95% UI 273.7 to 596.5), and East Asia (356.4, 95% UI 233.2 to 513.2). High-income North America (17.0, 95% UI 9.0 to 25.4%) had the largest increases in YLD of neck pain per 100,000 population from 1990 to 2019. At the national level, the highest age-standardized YLD of neck pain was found in the Philippines (530.1, 95% UI 350.6 to 764.8) and the highest change age-standardized YLD between 1990 and 2019 was found in the United States (18.4, 95% UI 9.9 to 27.6%). Overall, the global burden of neck pain increased with age until the age of 70–74 years, and was higher in women than men. In general, positive associations between socio-demographic index and burden of neck pain were found. Conclusions Because neck pain is a major public health burden with a high prevalence, incidence, and YLD worldwide, it is important to update its epidemiological data and trends to cope with the future burden of neck pain.

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Global, regional, and national neck pain burden in the general population, 1990–2019: An analysis of the global burden of disease study 2019

Background To comprehensively analyze the global level and trends of prevalence, incidence and years lived with disability (YLDs) for low back pain (LBP) from 1990 to 2019 by age, sex and sociodemographic index (SDI). Methods Publicly available modelled data and methods were obtained from the Global Burden of Diseases (GBD) study 2019, and used to evaluate the global burden of LBP through a systematic analysis. Results Globally, the age-standardized prevalence, incidence and YLDs rate of LBP were slightly decreased from 1990 to 2019, but the number of the prevalent cases, incident cases and YLDs had substantially increased, and LBP remains the leading cause of YLDs in 2019 worldwide. The number of prevalent cases was increased with age and peaked at the age of 45–54 years for both sexes, and the global prevalence rate was higher in females than in males and increased with age, peaking at the 80–84 age group in both sexes in 2019. Overall, a positive association between the age-standardized YLD rate and SDI was observed over the past thirty years. At the national revel, the United States, Denmark and Switzerland had the three highest levels of age-standardized prevalence, while Zambia, Zimbabwe and Canada showed the highest increase in the age-standardized prevalence during 1990–2019. Conclusions LBP is a major public health issue globally, and its burden remains high. Increasing population awareness about its risk factors and preventive measures for LBP are needed to reduce the future burden of this condition. The translational potential of this article Due to the high prevalence and heavy burden of LBP globally, it is important to update its epidemiological data. This systematic analysis provides researchers and healthcare policy makers with up-to-date, comprehensive and comparable information on global LBP burden, which is of clinical translational significance.

Mingjue Chen

Papers

Global, regional and national burden of low back pain 1990–2019: A systematic analysis of the Global Burden of Disease study 2019