Pain Regulation by Peripheral Glutamate and its Abnormalities

The activities of primary sensory nerves that branch off from the dorsal root and trigeminal ganglia are important for understanding the reception and transmission of a wide variety of painful and nonpainful sensations, such as touch, and temperature. Glutamate is well-established as a principal neurotransmitter in the central nervous system; however, it also works as a peripheral mediator to regulate neuronal and non-neuronal cells. Many studies have revealed that peripheral glutamate is one of the endogenous pro-nociceptive mediators that decreases the threshold for nociceptive stimuli through changing sensitivities of nociceptors and membrane excitabilities in sensory afferents. Here we reviewed the knowledge about the functions of peripheral glutamate in pain regulation and its abnormalities under pathophysiological conditions.