Targeting the D series resolvin receptor system for the treatment of osteoarthritis pain

Autor: Junting Huang, Paul I. Mapp, Brigitte E. Scammell, Sadaf Ashraf, Andrew J. Bennett, Srinivasarao Ravipati, David A. Barrett, Petros Pousinis, Victoria Chapman, James J. Burston, Li Li
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Cartilage
Articular
0301 basic medicine
Pathology
medicine.medical_treatment
Gene Expression
Osteoarthritis
Pharmacology
Menisci
Tibial
chemistry.chemical_compound
0302 clinical medicine
Immunology and Allergy
Enzyme Inhibitors
Receptors
Lipoxin
Receptor
Behavior
Animal
Microglia
Synovial Membrane
Osteoarthritis
Knee
Arthralgia
Iodoacetic Acid
Astrogliosis
medicine.anatomical_structure
Spinal Cord
Joint pain
Receptors
Chemokine
Arachidonic acid
medicine.symptom
Neuroglia
Resolvin
medicine.medical_specialty
Docosahexaenoic Acids
Joint replacement
Immunology
Real-Time Polymerase Chain Reaction
03 medical and health sciences
Rheumatology
medicine
Animals
Humans
RNA
Messenger
Adaptor Proteins
Signal Transducing
business.industry
medicine.disease
Rats
Disease Models
Animal
030104 developmental biology
chemistry
business
030217 neurology & neurosurgery
Zdroj: Arthritis & Rheumatology (Hoboken, N.j.)
ISSN: 2326-5191
Popis: Objective Pain is a major symptom of osteoarthritis (OA); currently available analgesics either do not provide adequate pain relief or are associated with serious side effects. The aim of this study was to investigate the therapeutic potential of targeting the resolvin receptor system to modify OA pain and pathology. Methods Gene expression of 2 resolvin receptors (ALX and ChemR23) was quantified in synovium and medial tibial plateau specimens obtained from patients with OA at the time of joint replacement surgery. Two models of OA joint pain were used for the mechanistic studies. Gene expression in the joint and central nervous system was quantified. The effects of exogenous administration of the D series resolvin precursor 17(R)‐hydroxy‐docosahexaenoic acid (17[R]‐HDoHE) on pain behavior, joint pathology, spinal microglia, and astroglyosis were quantified. Plasma levels of relevant lipids, resolvin D2, 17(R)‐HDoHE, and arachidonic acid, were determined in rats, using liquid chromatography tandem mass spectrometry. Results There was a positive correlation between resolvin receptor and interleukin‐6 (IL‐6) expression in human OA synovial and medial tibial plateau tissue. In rats, synovial expression of ALX was positively correlated with expression of IL‐1β, tumor necrosis factor, and cyclooxygenase 2. Treatment with 17(R)‐HDoHE reversed established pain behavior (but not joint pathology) in 2 models of OA pain. This was associated with a significant elevation in the plasma levels of resolvin D2 and a significant reduction in astrogliosis in the spinal cord in the monosodium iodoacetate–induced OA rat model. Conclusion Our preclinical data demonstrate the robust analgesic effects of activation of the D series resolvin pathways in 2 different animal models of OA. Our data support a predominant central mechanism of action in clinically relevant models of OA pain.
Databáze: OpenAIRE
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