Dataset Information

Targeting neurotrophic factors: Novel approaches to musculoskeletal pain.

ABSTRACT: Chronic pain represents a substantial unmet medical need globally. In recent years, the quest for a new generation of novel, safe, mechanism-based analgesic treatments has focused on neurotrophic factors, a large group of secreted proteins that control the growth and survival of different populations of neurons, but that postnatally are involved in the genesis and maintenance of pain, with biological activity in both the periphery and the central nervous system. In this narrative review, we discuss the two families of neurotrophic proteins that have been extensively studied for their role in pain: first, the neurotrophins, nerve growth factor (NGF) and brain-derived growth factor (BDNF), and secondly, the GDNF family of ligands (GFLs). We provide an overview of the pain pathway, and the pain-producing effects of these different proteins. We summarize accumulating preclinical and clinical findings with a focus on musculoskeletal pain, and on osteoarthritis in particular, because the musculoskeletal system is the most prevalent source of chronic pain and of disability, and clinical testing of these novel agents - often biologics- is most advanced in this area.

SUBMITTER: Malfait AM

PROVIDER: S-EPMC7938761 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Targeting neurotrophic factors: Novel approaches to musculoskeletal pain.

Malfait Anne-Marie AM Miller Rachel E RE Block Joel A JA

Pharmacology & therapeutics 20200418

Chronic pain represents a substantial unmet medical need globally. In recent years, the quest for a new generation of novel, safe, mechanism-based analgesic treatments has focused on neurotrophic factors, a large group of secreted proteins that control the growth and survival of different populations of neurons, but that postnatally are involved in the genesis and maintenance of pain, with biological activity in both the periphery and the central nervous system. In this narrative review, we disc ...[more]

PMID: 32311372

Similar Datasets

Project description:BackgroundMusculoskeletal pain conditions incur high costs and produce significant personal and public health consequences, including disability and opioid-related mortality. Persistence of high-cost health care utilization for musculoskeletal pain may help identify system inefficiencies that could limit value of care. The objective of this study was to identify factors associated with persistent high-cost utilization among individuals seeking health care for musculoskeletal pain.MethodsThis was a retrospective cohort study of Medical Expenditure Panel Survey data (2008-2013) that included a non-institutionalized, population-based sample of individuals seeking health care for a musculoskeletal pain condition (n = 12,985). Expenditures associated with musculoskeletal pain conditions over two consecutive years were analyzed from prescribed medicine, office-based medical provider visits, outpatient department visits, emergency room visits, inpatient hospital stays, and home health visits. Persistent high-cost utilization was defined as being in the top 15th percentile for annual musculoskeletal pain-related expenditures over 2 consecutive years. We used multinomial regression to determine which modifiable and non-modifiable sociodemographic, health, and pain-related variables were associated with persistent high-cost utilization.ResultsApproximately 35% of direct costs for musculoskeletal pain were concentrated among the 4% defined as persistent high-cost utilizers. Non-modifiable variables associated with expenditure group classification included age, race, poverty level, geographic region, insurance status, diagnosis type and total number of musculoskeletal pain diagnoses. Modifiable variables associated with increased risk of high expenditure classification were higher number of missed work days, greater pain interference, and higher use of prescription medication for pain, while higher self-reported physical and mental health were associated with lower risk of high expenditure classification.ConclusionsHealth care delivery models that prospectively identify these potentially modifiable factors may improve the costs and value of care for individuals with musculoskeletal pain prone to risk for high-cost care episodes.

Project description:BackgroundLow back pain (LBP) is the leading cause of years lived with disability worldwide. Most people with LBP receive the diagnosis of nonspecific LBP or sciatica. Medications are commonly prescribed but have limited analgesic effects and are associated with adverse events. A novel treatment approach is to target neurotrophins such as nerve growth factor (NGF) to reduce pain intensity. NGF inhibitors have been tested in some randomized controlled trials (RCTs) in recent years, showing promise for the treatment of chronic LBP; however, their efficacy and safety need to be evaluated to guide regulatory actions.ObjectiveThe aim of this study is to evaluate the efficacy and safety of medicines targeting neurotrophins in patients with LBP and sciatica.MethodsIn this systematic review, we will include published and unpublished records of parallel RCTs and the first phase of crossover RCTs that compare the effects of medicines targeting neurotrophins with any control group. We will search the CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, EU Clinical Trials Register, and WHO International Clinical Registry Platform databases from inception. Pairs of authors will independently screen the records for eligibility, and we will independently extract data in duplicate. We will conduct a quantitative synthesis (meta-analysis) with the studies that report sufficient data and compare the medicines of interest versus placebo. We will use random-effects models and calculate estimates of effects and heterogeneity for each outcome. We will assess the risk of bias for each study using the Cochrane Collaboration tool, and form judgments of confidence in the evidence according to GRADE recommendations. We will use the PRISMA statement to report the findings. We plan to conduct subgroup analyses by condition, type of medication, and time point. We will also assess the impact of a potential new trial on an existing meta-analysis. Data from studies that meet inclusion criteria but cannot be included in the meta-analysis will be reported narratively.ResultsThe protocol was registered on the Open Science Framework on May 19, 2020. As of December 2020, we have identified 1932 records.ConclusionsThis systematic review and meta-analysis will assess the evidence for the efficacy and safety of NGF inhibitors for pain in patients with nonspecific LBP and sciatica. The inclusion of new studies and unpublished data may improve the precision of the effect estimates and guide regulatory actions of the medications for LBP and sciatica.Trial registrationOpen Science Framework; https://osf.io/b8adn/.International registered report identifier (irrid)DERR1-10.2196/22905.

Dataset Information

Targeting neurotrophic factors: Novel approaches to musculoskeletal pain.

Publications

Targeting neurotrophic factors: Novel approaches to musculoskeletal pain.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets