Activation of nociceptive reflexes by peripheral kainate receptors.

The rat isolated spinal cord-tail preparation was used to examine the ability of peripherally applied excitatory amino acids to stimulate ventral root reflexes. Bolus applications (3 sec) of domoate (0.1-10 microM) or kainate (KA; 10-300 microM) to exposed skin of the rat tail stimulated ventral root responses comparably to those evoked by capsaicin (0.3-10 microM) or bradykinin (0.1-10 microM). The ventral root potential evoked by both capsaicin and KA is thought to be a nociceptive response because both compounds selectively activate peripheral C-fibers. L-Glutamate (0.01-10 mM), quisqualate (0.1-1 mM) and amino-5-methyl-4-isoxazole-propionic acid (0.1-1.0 mM) were of lower potency than KA, whereas N-methyl-D-aspartate (1 mM) and L-aspartate (10 mM) were inactive. Responses evoked by prolonged application of KA faded rapidly. Capsaicin-evoked responses partially faded during prolonged application, but residual spiking activity was recorded for at least 30 min. KA did not evoke any observable response during application of capsaicin. The effects of KA and capsaicin were blocked by spinal application of morphine (0.3-1.0 microM) in a naloxone-reversible manner, consistent with activation of peripheral nociceptive afferents. The action of KA, but not capsaicin, was competitively inhibited by the amino-5-methyl-4-isoxazole-propionic acid/KA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (10-100 microM) applied to the rat tail (pA2 = 5.9). Conversely, ruthenium red (1 microM) selectively blocked capsaicin-evoked nociceptive reflexes. The existence of functional KA receptors on nociceptive afferents suggests that peripherally released glutamate or other excitatory amino acids could be involved in nociception or neurogenic inflammation.