L-glutamate activates peripheral nociceptors.

The chemosensitivity of nociceptive afferents has been investigated using the isolated spinal-cord-tail preparation of the neonatal rat. L-glutamate applied to exposed rat tail skin stimulated nociceptive reflexes (ED50 = 136 microM). The action of L-glutamate was selective, since other constitutive L-amino acids or D-glutamate were inactive at a concentration of 10 mM. The known algogens bradykinin, acetylcholine, serotonin and potassium ions also stimulated nociceptive reflexes. Histamine (1 mM) and substance P (0.1 mM) had no observable effect. L-glutamate, which is released from macrophages, could therefore contribute to inflammation-related nociception by stimulation of cutaneous nociceptive nerve endings.