Inflammation-induced changes in peripheral glutamate receptor populations

The ionotropic glutamate receptors N-methyl-D-aspartate (NMDA), alpha-amino -3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) have been localized on subpopulations of unmyelinated and myelinated sensory axo ns in normal skin. Behavioral studies indicate that activation of these rec eptors results in nociceptive behaviors and contributes to inflammatory pai n. The goal of the present study was to determine if these glutamate recept ors might contribute to the:peripheral hypersensitivity observed in inflamm ation. The major findings were that 48 h following complete Freund's adljuv ant (CFA)-induced inflammation, the proportions of unmyelinated axons label ed for NMDA, AMPA or KA receptors were 61%, 43% and 48%, respectively, in c utaneous nerves in the inflamed paw compared to 48%, 22% and 27%, respectiv ely, in the non-inflamed paw. The proportions of myelinated axons labeled f or NMDA, AMPA or KA receptors were 61%, 61% and 43%, respectively, compared to 43%, 42% and 28%, respectively, in the non-inflamed hindpaw. These incr eases were all significant. These data indicate that the number of sensory axons containing ionotropic glutamate receptors increases during inflammati on, and this may be a contributing factor to peripheral sensitization in in flammation. (C) 1999 Elsevier Science B.V. All rights reserved.