The excitatory neurotransmitter glutamate and its receptors: the culprits behind neuropathic pain?

Abstract

Human understanding of the nature of pain has undergone a profound shift from mechanical reductionism to a multidimensional, integrative approach. Among the many types of chronic pain, neuropathic pain (NP) has long been a key focus of research in the fields of neurobiology and pain medicine, owing to its high prevalence and complex mechanisms. Its core pathological feature is an abnormal increase in neuron excitability caused by peripheral and central sensitization. As the most important excitatory neurotransmitter in the nervous system, glutamate plays an irreplaceable and central role in signal transduction at every level of the pain transmission pathway. Therefore, investigating the mechanisms of analgesic effects mediated by glutamate and its receptors is of great significance for understanding the pathophysiological nature of NP. This paper focuses on the mechanisms of peripheral and central sensitisation mediated by glutamate and its receptors, exploring their potential effects as key analgesic targets in NP, with a view to providing a theoretical foundation and directions for clinical translation in research into the analgesic mechanisms of NP.