Glutamate-induced excitation and sensitization of nociceptors in rat glabrous skin

Anatomical studies demonstrate the presence of glutamate receptors on unmye linated axons in peripheral cutaneous nerves. Pharmacological studies show that intraplantar injection of glutamate or glutamate agonists in the glabr ous skin results in nociceptive behaviors. The present study describes a no vel in vitro skin-nerve preparation using the glabrous skin from the rat hi ndpaw. In the first series of experiments, recordings were obtained from 14 1 fibers that responded to a strong mechanical search stimulus. Based on th eir conduction velocity they were classified as C (27%). A delta (28%) and A beta (45%) fibers. The C and A delta fibers typically exhibited sustained firing during suprathreshold mechanical stimuli whereas both rapidly (66%) and slowly (34%) adapting responses were obtained from A beta fibers. Noxi ous heat excited 46% of the C fibers but only 12% of the A delta units. In another series of experiments application of an ascending series of glutama te concentrations (10, 100, 300, and 1000 muM) to A delta (n = 14) and C (n = 19) nociceptors resulted in a significant excitation of 43% (6/14) A del ta fibers and 68% (13/19) C fibers. At these concentrations, there was no e xcitation of A beta units (,I = 13). Superfusion of the receptive fields of either mechanoheat-sensitive: A (AMH, n = 10) or C fibers (CMW, n = 12) fo r 2 min with 300 muM glutamate resulted in sensitization of 90% (9/10) AMH and 92% (11/12) CMH fibers to subsequent thermal stimulation. This was evid enced by a significant (1) decrease in thermal threshold for activation, (2 ) increase in discharge rate, and (3) increase in peak instantaneous freque ncies during the second heat trial. Glutamate-induced sensitization to heat occurred in the absence of either a glutamate-induced excitation or an ini tial heat response. Exposure of A delta or C fibers to glutamate did not re sult in a decrease in von Frey thresholds. These data provide a physiologic al basis for the nociceptive behaviors that arise following intraplantar in jection of glutamate or glutamate agonists. Furthermore, demonstration of g lutamate-induced excitation and heat sensitization of nociceptors indicates that local or topical administration of glutamate receptor antagonists may have therapeutic potential for the treatment of pain. (C) 2001 Internation al Association for the Study of Pain. Published by Elsevier Science B.V. Al l rights reserved.