Plasticity in pain control systems may play an important role in clinical pain and some mechanisms of plasticity may be similar to those involved in learning. In this study we investigate the importance of alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors for the maintenance of long-term potentiation (LTP) in wide dynamic range (WDR) neurons. Doses of 6-nitro-7-sulphomoylbenzoylquinoxaline-2,3-dione disodium (NBQX) and D-Q-amino-5-phosphonopentanoic acid (D-AP5) equipotent in reducing C-fiber mediated responses in controls, reduced the established LTP by about 50 and 80%, respectively. The drug effect lasted less than 1 h in controls. After induction of LTP, NBQX caused a reversible reduction of the potentiation. D-AP5, however, caused a stronger attenuation of the LTP, outlasting the effect of the drug in controls. We suggest that both pre-emptive analgesia preventing LTP induction and an early reduction of the excitation of neurons is important for the inhibition of LTP and central sensitization. Thus, it is possible that an early antinociceptive treatment preventing an excessive excitation of neurons in the dorsal horn may be of importance in preventing longlasting and pathological pain states.