Effects of electroacupuncture with different frequencies on spinal ionotropic glutamate receptor expression in complete Freund's adjuvant-injected rat

We investigated expressional changes of spinal glutamate receptors by electroacupuncture (EA) in an inflammatory animal model. Inflammation was induced by an intraplantar injection of complete Freund's adjuvant (CFA) into the hindpaw of male Sprague-Dawley rats. Bilateral EA stimulation at 2, 15 and 120 Hz was applied at those acupoints corresponding to Zusanli and Sanyinjiao in man using needles with 3-day intervals for 30 days. Paw edema and mechanical thresholds were measured by a water displacement plethysmometer and Analgesy-Meter, respectively. Edema and mechanical sensitivity of the hindpaw induced by CFA-injection were strongly inhibited by EA stimulation. At 30 days after CFA-injection, effects of EA on ionotropic glutamate receptor (NR-1, NR-2A, GluR-1 and GluR-2/3) expression in association with c-fos and calcitonin gene-related peptide (CGRP) expression were observed in the dorsal horn of the spinal cord using immunohistochemistry. The number of c-fos-like immunostained cells was decreased significantly in the superficial laminae of the dorsal horn by 2 Hz EA, but CGRP expression also showed a marked decrease in the same region using the other types of EA stimulation. N-methyl-d-aspartate receptor (NR-1 and NR-2A) expression was attenuated in all regions of the dorsal horn by all types of EA. Of the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (GluR-1 and -2/3), only GluR-1 expression was prevented by EA treatment in the superficial laminae and the neck of the dorsal horn. It is concluded that EA treatment can attenuate inflammatory edema and mechanical thresholds in CFA-injected rats through modulating expression of ionotropic glutamate receptors, and especially N-methyl-d-aspartate receptors, in the dorsal horn of the spinal cord.