Involvement of N-methyl-D-aspartate-type glutamate receptor epsilon1 and epsilon4 subunits in tonic inflammatory pain and neuropathic pain.

N-methyl-D-aspartate receptors play an important role in nociceptive transmissions in various types of pain. In this study, we investigated the pain-related response in mice lacking the N-methyl-D-aspartate-type glutamate receptor epsilon1 or epsilon4 subunit in the formalin test and in the partial sciatic nerve ligation-induced neuropathic pain model. The second tonic inflammatory phase response in the formalin test was significantly reduced in glutamate receptor epsilon1 knockout epsilon1(-/-) mice, but not in glutamate receptor epsilon4(-/-) when compared with wild-type mice. In the partial sciatic nerve ligation model, glutamate receptor epsilon1(-/-) mice exhibited no difference in mechanical allodynia compared with wild-type mice. Glutamate receptor epsilon4(-/-) mice, however, failed to develop allodynia after the nerve ligation. These results suggest that glutamate receptor epsilon1 and epsilon4 subunits are involved in tonic inflammatory pain and neuropathic allodynia, respectively.