Pharmacology Notes

At the first central synapse, A-delta- and C-fibre input to the dorsal horn from peripheral nociceptor activation (eg tissue injury) results in the release of the excitatory neurotransmitters glutamate and substance P. Glutamate acts on the ionotropic alfa-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor on the second-order nociceptive dorsal horn cell and, depending on the magnitude and duration of the stimulus, results in an impulse being triggered in the dorsal horn neurone which propagates as nociceptive information to the brain where it may be perceived as pain. If the stimulus is stronger or sustained, substance P is released from the C-fibre terminal and activates the neurokinin 1 (NK1) receptor, which results in a lowering of the threshold of the dorsal horn neurone, further enhancing activity. Even more intense or prolonged stimuli may activate the N-methyl-D-aspartate (NMDA) receptor.