Vol. 300, Issue 2, 513-520, February 2002

Plasticity in Excitatory Amino Acid Receptor-Mediated Descending Pain Modulation after Inflammation

Yun Guan, Ryuji Terayama, Ronald Dubner and Ke Ren

Department of Oral and Craniofacial Biological Sciences, Dental School, and Program in Neuroscience, University of Maryland, Baltimore, Maryland

The role for excitatory amino acids (EAAs) in the rostral ventromedial medulla (RVM) in descending pain modulation after persistent noxious input is unclear. In an animal model of inflammatory hyperalgesia, we examined the effects of intra-RVM microinjection of EAA receptor agonists and antagonists on paw withdrawal and tail-flick responses in lightly anesthetized rats. N-Methyl-D-aspartate (NMDA) produced effects that depended upon the postinflammatory time period. At 3 h postinflammation, NMDA induced facilitation at a lower dose (10 pmol) and inhibition at a higher dose (1000 pmol). At 24 h postinflammation, NMDA (0.1-1000 pmol) produced a dose-dependent inhibition. The facilitation and inhibition, respectively, were attenuated significantly by the preadministration of an NMDA receptor antagonist, DL-2-amino-5-phosphonovaleric acid (APV) (10 pmol, P < 0.05), to the same site. Intra-RVM microinjection of -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) (0.1-100 pmol) produced dose-dependent inhibition at both 3 and 24 h postinflammation that was blocked by the preadministration of an AMPA/kainate receptor antagonist, 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline (100 pmol, P < 0.05). Unexpectedly, AMPA-produced inhibition was also significantly attenuated by preadministration of APV (10 pmol, P < 0.05). Compared with 3 h postinflammation, both NMDA and AMPA showed a leftward shift in their dose-response curves at 24 h postinflammation. These results demonstrate that NMDA and AMPA receptors in the RVM are involved in the descending modulation after inflammatory hyperalgesia. There is a time-dependent increase in EAA neurotransmission in the RVM after inflammation and NMDA receptors play an important role in AMPA-produced inhibition.