Taken together, the study identifies that sympathetic nerves, via the release of the neurotransmitter NE, enhance the growth of sensory nerve endings in subchondral bone, activate sensory neurons, and co-operate with local neuroactive factors netrin-1 and PGE2 in the subchondral bone to exacerbate osteoarthritis-related pain. The gene discussed is NTN1; the disease is osteoarthritis.