Excitatory amino acid glutamate: role in peripheral nociceptive transduction and inflammation in experimental and clinical osteoarthritis

Although a large proportion of patients with osteoarthritis (OA) show inflammation in their affected joints, the pathological role of inflammation in the development and progression of OA has yet to be clarified. Glutamate is considered an excitatory amino acid (EAA) neurotransmitter in the mammalian central nervous system (CNS). There are cellular membrane glutamate receptors and transporters for signal input modulation and termination as well as vesicular glutamate transporters (VGLUTs) for signal output through exocytotic release. Glutamate been shown to mediate intercellular communications in bone cells in a manner similar to synaptic transmission within the CNS. Glutamate-mediated events may also contribute to the pathogenesis and ongoing processes of peripheral nociceptive transduction and inflammation of experimental arthritis models as well as human arthritic conditions. This review will discuss the differential roles of glutamate signaling and blockade in peripheral neuronal and non-neuronal joint tissues, including bone remodeling systems and their potentials to impact OA-related inflammation and progression. This will serve to identify several potential targets to direct novel therapies for OA. Future studies will further elucidate the role of glutamate in the development and progression of OA, as well as its association with the clinical features of the disease.