Glutamic acid, or glutamate, is the major excitatory small molecule neurotransmitter in the central nervous system (CNS) of mammals, expressed in neurons and glia. In response to depolarization, glutamate is released from a neuron's presynaptic nerve ending, where it binds and activates receptors on opposing postsynaptic neurons, which, depending on the receptor type, results in either excitation or inhibition of a given postsynaptic neuron. Glutamate receptors are either ion-forming channels (ionotropic) or G-protein coupled receptors (metabotropic). Stimulation of ionotropic receptors, such as N-methyl-D-aspartate (NMDA) and non-NMDA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA] and kainic acid [KA]), causes excitation of postsynaptic neurons, while stimulation of metabotropic receptors (groups I, II, and III) causes inhibition of postsynaptic neurons.9
Animal studies suggest that during migraine, activated primary sensory neurons (meningeal nociceptors) may release the excitatory neurotransmitter glutamate from their centrally projecting nerve endings within the trigeminal nucleus caudalis (TNC), which binds to postjunctional glutamate receptors (NMDA, non-NMDA, and/or metabotropic glutamate [mGlu] subtypes). This activates second-order TNC neurons (labeled as postjunction cell), which are involved in the relay of information to brain regions mediating headache pain perception.9,10
The activation of the glutamatergic NMDA receptors on the postsynaptic second-order neurons in the TNC plays a key role in the establishment of central sensitization.9,10
9. Buchanan TM, Ramadan NM, Aurora S.
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10: Ramadan NM, Buchanan TM. New and future migraine therapy. Pharmacol
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2006;112:199–212.
