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The activated primary nociceptive afferent from the periphery releases glutamate at the second-order sensory neuron in the dorsal horn of the spinal cord, which binds to N-methyl-D-aspartate (NMDA) receptors. Ketamine blocks the NMDA receptor, which attenuates the development of central sensitization as well as opioid tolerance and hyperalgesia.
− = block; + = increase.
Adapted from Gorlin et al.22.
