Neuropeptides: important regulators of joint homeostasis.

ABSTRACT

PURPOSE: This review explores the mechanisms of joint pain with a special focus on the role of neuropeptides in pain transmission and their potential role in the progression of joint degeneration as seen in osteoarthritis. METHODS: A literature search was performed on papers published between January 1990 and September 2017 using the Web of Science Core Collection, MEDLINE and Scopus databases. RESULTS: What is seen in the subchondral bone and synovia is mirrored in the central nervous system (CNS). Substance P, calcitonin gene-related peptide, vasoactive intestinal peptide and neuropeptide Y are the major peptides involved both in the generation of pain as well as reducing pain post-joint trauma. The interplay between them and other neuropeptides and cytokines influence how noxious stimuli are transduced, transmitted and modulated for a final pain perception as part of a complex cascade of events. There is a close interaction between the different components in the joint that together cross-talk to adapt to load and catabolic factors during injury and inflammation. CONCLUSION: The articular joint should be seen as an organ where local joint pain development and maintenance is influenced by interplay between the local transmitters in the joints as well as their dependence on the CNS. A slow-release cocktail of mixed antibodies targeted against neuropeptides and receptor blockers/stimulators involved in the events of early joint pain or any inflammatory joint disease is a future treatment target. LEVEL OF EVIDENCE V.