Evidence for an inflammation-induced change in the local glutamatergic regulation of postganglionic sympathetic efferents

Abstract

Sympathetic efferents are involved in the pain of inflammation. Thus the control of these fibers is a matter of considerable importance. In this regard, postganglionic sympathetic fibers in normal rats express ionotropic glutamate receptors. The present study tests the hypothesis that inflammation leads to a significant increase in numbers of sympathetic efferents that express these receptors. In normal rats, the percentage of fibers in the L4 and L5 sympathetic gray rami immunostained with antibodies against subunits of NMDA (NMDAR1), AMPA (GluR1), or kainate (GluR5,6,7) receptors are 29, 5 and 5%, respectively. Forty-eight hours following injection of complete Freund's adjuvant into one hindpaw, the percentages of fibers in the ipsilateral gray rami immunostained for NMDA, AMPA or kainate are 57, 52 and 48%, respectively. Thus, following inflammation there is a two-fold increase in axons expressing NMDA receptors and a ten-fold increase in axons expressing AMPA or kainate receptors. These data suggest that postganglionic activity may be enhanced by glutamate receptor activation during inflammation. Increased activity in postganglionic fibers could lead to an increased release of NE and other substances in postganglionic efferents such as prostaglandins which in turn could enhance nociceptor activity. This change in glutamate receptor organization offers a possible site of pharmacological intervention for the maladaptive symptoms that often arise following peripheral inflammation.