Modulation of the glutamatergic system in neuropathic pain: The role of pregabalin

Neuropathic pain is a chronic pain condition caused by damage or disease of the somatosensory nervous system and is often resistant to conventional analgesic therapy.This condition involves complex pathophysiological mechanisms, including peripheral and central sensitization, neuroinflammation, and changes in synaptic plasticity.Dysfunction of the glutamatergic system, characterized by increased glutamate release and hyperactivation of glutamate receptors, plays a crucial role in maintaining neuronal excitability and persistent pain transmission.This review aims to examine the role of the glutamatergic system in the pathophysiology of neuropathic pain and to evaluate the effectiveness of pregabalin as an indirect modulator of the glutamatergic system in the management of neuropathic pain.This research is a narrative review based on a review of relevant scientific literature from international publications, including experimental studies, clinical trials, and review articles discussing neuropathic pain, modulation of the glutamatergic system, and the use of pregabalin.The review results indicate that glutamate accumulation and dysregulation of glutamate transporters lead to excessive activation of ionotropic and metabotropic glutamate receptors, which contributes to central sensitization.Pregabalin works by binding to the α2δ subunit of presynaptic calcium channels, thereby decreasing the release of glutamate and other excitatory neurotransmitters, as well as improving glutamate synaptic regulation, which impacts reducing pain intensity and improving patient quality of life.The glutamatergic system is an important therapeutic target in neuropathic pain.Pregabalin is effective as a first-line therapy through indirect modulation of the glutamatergic system, although its use still requires monitoring for side effects and individual patient response.