title: Emerging Targets for the Management of Osteoarthritis Pain.
abstract: Worldwide, osteoarthritis (OA) is one of the leading causes of chronic pain, for which adequate relief is not available. Ongoing peripheral input from the affected joint is a major factor in OA-associated pain. Therefore, this review focuses predominantly on peripheral targets emerging in the preclinical and clinical arena. Nerve growth factor is the most advanced of these targets, and its blockade has shown tremendous promise in clinical trials in knee OA. A number of different types of ion channels, including voltage-gated sodium channels and calcium channels, transient receptor potential channels, and acid-sensing ion channels, are important for neuronal excitability and play a role in pain genesis. Few channel blockers have been tested in preclinical models of OA, with varying results. Finally, we discuss some examples of G-protein coupled receptors, which may offer attractive therapeutic strategies for OA pain, including receptors for bradykinin, calcitonin gene-related peptide, and chemokines. Since many of the pathways described above can be selectively and potently targeted, they offer an exciting opportunity for pain management in OA, either systemically or locally.
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, Rush University Medical Center, 1611 W Harrison Street, Suite 510, Chicago, IL, 60612, USA. anne-marie_malfait@rush.edu.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Malfait
authors.affiliation: Department of Pharmacology, Northwestern University, Robert H. Lurie Medical Research Center, 303 E. Superior, Chicago, IL, 60613, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Miller
mesh_terms: D062646:Acid Sensing Ion Channel Blockers / Q000627:therapeutic use; D062565:Acid Sensing Ion Channels / Q000378:metabolism; D018771:Arthralgia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D065168:Bradykinin Receptor Antagonists / Q000627:therapeutic use; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D015220:Calcium Channels / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D010003:Osteoarthritis / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D018002:Receptors, Bradykinin / Q000378:metabolism; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D061567:Voltage-Gated Sodium Channel Blockers / Q000627:therapeutic use; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism
chemical_list: D062646:Acid Sensing Ion Channel Blockers; D062565:Acid Sensing Ion Channels; D065168:Bradykinin Receptor Antagonists; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018002:Receptors, Bradykinin; D018015:Receptors, Calcitonin Gene-Related Peptide; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; D050051:Transient Receptor Potential Channels; D061567:Voltage-Gated Sodium Channel Blockers; D061566:Voltage-Gated Sodium Channels; D020932:Nerve Growth Factor
keywords: GPCRs; Ion channels; Nerve growth factor; Osteoarthritis; Pain; Targets