Could abnormal nerve growth help keep arthritic joints painful?

Details

Many forms of arthritis involve significant chronic joint pain. This experimental mouse study investigated whether sensory and sympathetic nerve fibers sprout significantly in painful arthritic knee joints, and whether nerve growth factor (NGF) drives this abnormal reorganization.

Researchers induced painful knee arthritis by injecting Freund's complete adjuvant (CFA) into the knee joints of young adult mice. CFA-injected mice then received systemic treatment with either vehicle or an anti-NGF antibody. Pain behaviors were assessed. At 28 days after the initial CFA injection, knee joints were processed for immunohistochemistry using antibodies against calcitonin gene-related peptide (CGRP; sensory nerve fibers), neurofilament 200 kd (NF200; sensory nerve fibers), growth-associated protein 43 (GAP-43; sprouted nerve fibers), tyrosine hydroxylase (TH; sympathetic nerve fibers), CD31 (endothelial cells), or CD68 (monocytes/macrophages).

In CFA-injected mice, the synovium showed significantly increased densities of CD68+ macrophages, CD31+ blood vessels, and CGRP+, NF200+, GAP-43+, and TH+ nerve fibers. Joint pain-related behaviors also increased significantly. None of these findings were observed in sham-injected mice.

Anti-NGF treatment reduced pain-related behaviors and ectopic nerve-fiber sprouting, but had no significant effect on the increased density of CD31+ blood vessels or CD68+ macrophages.

The findings demonstrate that ectopic sprouting of sensory and sympathetic nerve fibers occurs in painful arthritic joints and may be involved in generating and maintaining arthritic pain.