Distributional changes in substance P nociceptive fiber patterns in naturally osteoarthritic articulations

Studies have proved the importance of substance P (SP) in the development and perpetuation of inflammation in joints, and describe the abundant SP neural network in the soft tissue structures of various articulations. Less information is available on the innervation of the bony structures of joints, and there is a paucity of data describing the changes associated with disease conditions. Our objectives were to evaluate changes in the distribution of sensory nerve fibers in the bony structures of naturally osteoarthritic joints.

Five osteoarthritic metacarpophalangeal (MCP) articulations were removed from 4 horses euthanized because of clinically severe and persistent lameness. The articulations were examined grossly and by high detail radiographs, and substance P containing nociceptive fibers were identified on thin sections by immunoreaction.

Gross examination and radiographs revealed evidence of osteoarthritis (OA), including thin, eroded, and fibrillated articular cartilage and, in the most severe cases, periarticular osteophytes and palmar metacarpal flattening with cystic cavitations. Histologically, there was a generalized loss of cartilage matrix basophilia, with chondrocyte clustering or death. SP nerve fibers were evident in the articular capsule and periosteum, and their appearance and frequency were similar to nonarthritic MCP articulations. Abnormal cartilage structures such as erosion channels and osteophytes on the dorsal proximal phalangeal perimeter contained short, tortuous, immunoreactive nerve fibers. Areas of chondrocyte cloning and abnormal fibrillated or eroded articular cartilage had increased generalized SP peptide staining, but no nerve fibers were identified. Additionally, hypercellular infiltrates in cystic cavitations in the subchondral bone stained intensely for SP, but true neurofilaments were absent.

Combined, the findings of SP innervation in areas of articular remodeling such as erosion channels and osteophytes suggest that SP plays a role in the signaling and maintenance of pain associated with OA.