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  1. NSLHD Research
  2. Research
  3. Research Publications
Please use this identifier to cite or link to this item: https://nslhd.intersearch.com.au/nslhdjspui/handle/1/37856
Title: Nerve Growth Factor (NGF) Inhibitors and Related Agents for Chronic Musculoskeletal Pain: A Comprehensive Review
Authors: Oo, Win Min ;Hunter, David J. 
Affiliation: Royal North Shore Hospital
Department: Rheumatology 
Issue Date: 2021
Publication information: 35(6):611-641
Journal: Biodrugs
Abstract: Musculoskeletal pain such as osteoarthritis (OA) and low back pain (LBP) are very common and contribute to enormous burden and societal costs, despite dramatic therapeutic advances over recent decades. Novel approaches and targeted therapies are required to satisfy the urgent unmet medical need of musculoskeletal pain relief in both conditions. Nerve growth factor (NGF) inhibitors have utilized novel mechanisms different from conventional drugs, which have a variety of gastrointestinal, cardiac, or renal adverse effects. Several phase 2/3 studies have been accomplished for these drugs, such as tanezumab, fasinumab, and tyrosine receptor kinase A (TrkA) inhibitors. We searched the literature using the PubMed database and clinical trials using ClinicalTrials.gov to identify original papers, meta-analyses as well as ongoing clinical trials assessing the efficacy and safety profile of these drugs. In this narrative review, we briefly overview the disease burden of musculoskeletal pain, the role of NGF signaling and its receptors in the genesis of pain, and the mechanisms of action of inhibitors of NGF signaling and downstream pathways, and then discuss the efficacy and safety of each investigational drug in OA and LBP. Finally, we briefly review two serious adverse effects of NGF inhibitors, namely rapidly progressive OA and sympathetic system effects, and conclude with possible barriers and potential research directions to overcome these.
URI: https://nslhd.intersearch.com.au/nslhdjspui/handle/1/37856
DOI: http://dx.doi.org/10.1007/s40259-021-00504-8
URL: https://link.springer.com/article/10.1007/s40259-021-00504-8
Type: Article
AHT Subjects: Musculoskeletal pain
Drug Therapy
Keywords: signal transduction;unmet medical need;*analgesic agent/ae [Adverse Drug Reaction];*analgesic agent/ct [Clinical Trial];*analgesic agent/dt [Drug Therapy];*analgesic agent/pd [Pharmacology];*analgesic agent/tm [Unexpected Outcome of Drug Treatment];fasinumab/dt [Drug Therapy];fasinumab/pd [Pharmacology];nerve growth factor/ec [Endogenous Compound];nerve growth factor receptor/ec [Endogenous Compound];tanezumab/dt [Drug Therapy];tanezumab/pd [Pharmacology];unclassified drug;NGF signaling;asp 7962/dt [Drug Therapy];asp 7962/pd [Pharmacology];gz 389988/dt [Drug Therapy];gz 389988/pd [Pharmacology];*nerve growth factor inhibitor/ae [Adverse Drug Reaction];*nerve growth factor inhibitor/ct [Clinical Trial];*nerve growth factor inhibitor/pd [Pharmacology];*nerve growth factor inhibitor/tm [Unexpected Outcome of Drug Treatment];ono 4474/dt [Drug Therapy];ono 4474/pd [Pharmacology];*nerve growth factor inhibitor/dt [Drug Therapy];adrenergic systemautonomic neuropathy/si [Side Effect];disease burden;drug efficacy;drug mechanism;drug safety;Humans;*low back pain/dt [Drug Therapy];*low back pain/et [Etiology];*musculoskeletal pain/dt [Drug Therapy];*musculoskeletal pain/et [Etiology];nonhuman;osteoarthritis/dt [Drug Therapy];osteoarthritis/si [Side Effect];phase 2 clinical trial (topic);phase 3 clinical trial (topic);review
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