Inflammation-induced up-regulation of ionotropic glutamate receptor expression in human skin

Background: N-methyl-D-aspartate (NMDA), -amino-3-hydroxy-5-methylisoxazolone-4-propionicacid (AMPA), and kainate (KA) receptors are members of the ionotropicglutamate receptor (iGluR) family and are increased in inflamedrat skin. These receptors contribute to inflammatory pain. Inthis study, we have examined whether there is a similar increasein iGluRs in inflamed human skin in the presence of inflammatorypain. Methods: Normal and inflamed-skin biopsies were obtained from eight patientsundergoing elective wound-debridement surgery. Real-time-polymerasechain reaction (PCR) and western blot analysis were used forquantitation of iGluR mRNA and protein in normal and inflamedhuman skin. Results: A significant increase in mRNA and protein for NMDA, AMPA, andKA receptor subunits was detected in inflamed compared withnormal skin. The amounts of NMDA (NR1 subunit), AMPA (GluR2subunit), and KA (GluR6 subunit) mRNA in inflamed skin weremean 6 (SD 1.6-fold), 2.5 (0.6-fold), and 3.8 (0.9-fold) (P<0.05),respectively, greater than that measured in normal skin. Theratio of NR1, GluR2, and GluR6 protein in inflamed comparedwith normal skin was 5.7 (1.2), 2.4 (0.5), and 3.6 (0.9) (P<0.05),respectively. Conclusions: These results, in human tissue, demonstrate that iGluR mRNAand protein expression are increased during persistent inflammationand that this increased activity may be involved in mediatingclinical inflammatory pain in human skin.