These effects suggest that persistent or chronic pain perception associated with MPS can involve numerous proinflammatory cytokines, neurotransmitters, and neuromodulators, including tumor necrosis factor-α (TNF-α), substance P, and cyclooxygenase-2 (COX-2), which relay pain signals from the peripheral to the central nervous system. This evidence concerns the gene PTGS2 and mucopolysaccharidosis.