Excitatory glutamatergic synaptic transmission in spinal dorsal horn

Excitatory glutamatergic synaptic transmission in the spinal dorsal horn is the primary physiological mechanism for the relay of nociceptive signals from the periphery to the central nervous system (StatPearls, 2023). This process involves the release of glutamate from primary afferent terminals and its subsequent activation of postsynaptic ionotropic receptors, including AMPA, NMDA, and kainate receptors, as well as metabotropic glutamate receptors (mGluRs) (PubMed, PMID: 29029618). Under conditions of chronic injury or inflammation, this pathway undergoes plastic changes known as central sensitization, which leads to an exaggerated response to painful stimuli (hyperalgesia) and pain from non-painful stimuli (allodynia) (Nature Reviews Neuroscience, 2011). Pharmacological targeting of this transmission involves the use of NMDA receptor antagonists, such as ketamine, or drugs that modulate presynaptic glutamate release, such as gabapentinoids (PubChem). While these interventions are effective for managing chronic pain, they are often limited by safety concerns such as sedation, ataxia, and cognitive impairment due to the ubiquitous role of glutamate in the central nervous system (NIH, 2022).

Other names

Glutamatergic signaling in the spinal dorsal hornSpinal excitatory neurotransmissionGlutamate-mediated nociceptive transmission

Modulation of excitatory signaling through the antagonism of postsynaptic glutamate receptors (NMDA, AMPA) or the inhibition of presynaptic glutamate release via voltage-gated calcium channel modulation.