Sympathetic Nerve Modulation of Joint Pathology in Adjuvant-Induced Arthritis
Background: There is increasing data suggesting a net increase in sympathetic tone plays an important role in rheumatoid arthritis. Several studies have reported altered distribution and density of autonomic nerves in patients with rheumatoid arthritis and animal models for the disease. This provides anatomical evidence that supports a neurally-mediated drive in inflammation and joint destruction. Methods: Adult rats were injected with complete Freund’s adjuvant. At 12 days post immunization, animals were randomly placed into a drug treatment group (SH1293, which interacts with - and ß2-ARs), an adjuvant arthritic group, or a control group. These animals were sacrificed at 14, 21, 28 and 126 days. The ankles were then evaluated for changes in lymphocytes, bone area, osteoclasts, cartilage, pannus, sympathetic nerves, and bone volume. Results: At 21 days, the drug treated group showed a significant improvement in lymphocytes, cartilage and bone volume. There was also a decrease in pannus and preservation of sympathetic nerves that was not significant. At 28 days, the drug treated group did not appear to show any significance, however, there was still an improvement in lymphocytes, pannus, and sympathetic nerves. The cartilage and bone volume became significantly less. Investigation of bone area and osteoclasts revealed 2 distinct groups. Some responded favorably to the drug while some responded less favorably. At both 21 and 28 days the high responding SH1293 rats showed a significant improvement in bone area and osteoclasts. There appears to be significant correlations between the variables and a strong general trend of joint preservation with the drug’s usage. At 126 days there were continued remodeling changes noted. Conclusion: Blocking increased sympathetic activity does alter bone metabolism in adjuvant-induced arthritic rats. These effects seem to be mediated by reduced norepinephrine interaction with adrenergic receptors peripherally.
Anatomy, Musculoskeletal Diseases, Musculoskeletal, Neural, and Ocular Physiology, Rheumatology, Arthritis - Rheumatoid; Sympathetic Nervous System; Nerve Growth Factors; Bone Remodeling; Anti-Inflammatory Agents - Non-steroidal; Macrophage Inflammatory Proteins; HLA Antigens; Receptors - Adrenergic;, Rheumatoid Arthritis; Autonomic Nerves; Freund's Adjuvant; Joint Destruction
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