Intact cartilage is not innervated with pain fibers, although with a disease, small pores at the osteochondral junction bring neurovascular inputs into deep layers of cartilage and could provide a source of pain. This study sought to quantify the relation between cartilage loss and worsening knee pain after adjusting for BMLs and synovitis at baseline and then examined whether the association of cartilage loss with worsening pain was mediated by worsening synovitis or change in bone marrow lesions (BMLs).
Cartilage thickness loss was associated with worsening knee pain after adjusting for coexistent BMLs and synovitis scores. While statistically significant, the relation between cartilage loss and worsening pain was, at best, modest with 0.1mm of cartilage loss associated with <1 point worsening on a 0–20 WOMAC pain scale. This suggests that it will be extremely hard to demonstrate that preventing cartilage loss reduces pain in a knee with OA. The association of cartilage loss with pain was mediated, in part, by worsening synovitis, but not change in BMLs.
There is considerable evidence that synovitis and BMLs are sources of pain in OA; it may be that this pain is not mostly triggered by cartilage loss. Cartilage thickness loss is weakly associated with knee pain, and the relationship is so weak as to call into question attempts to develop treatments that target only chondroprotection. The association with pain appears to be partially mediated by a change in synovitis and may be greater in those with no knee pain than in those with pre-existing pain.