Enhanced function of NR2C/2D-containing NMDA receptor in the nucleus accumbens contributes to peripheral nerve injury-induced neuropathic pain and depression in mice

Molecular Pain

Xiao-Hong Chen¹  Xiao-Bo Wu²  Huan-Jun Lu²  Peng-Bo Jing²  Yong-Jing Gao³ 

[1] Department of Anesthesiology, , Nantong, Jiangsu, China;Institute of Pain Medicine and Special Environmental Medicine, , Nantong, Jiangsu, China;Institute of Pain Medicine and Special Environmental Medicine, , Nantong, Jiangsu, China;Co-innovation Center of Neuroregeneration, , Nantong, Jiangsu, China;

关键词: Nucleus accumbens;    NMDA receptor;    NR2C;    NR2D;    neuropathic pain;    depression;   

DOI  :  10.1177/17448069211053255

来源: Sage Journals

【 摘 要 】

N-methyl-d-aspartate receptors (NMDARs) dysfunction in the nucleus accumbens (NAc) participates in regulating many neurological and psychiatric disorders such as drug addiction, chronic pain, and depression. NMDARs are heterotetrameric complexes generally composed of two NR1 and two NR2 subunits (NR2A, NR2B, NR2C and NR2D). Much attention has been focused on the role of NR2A and NR2B-containing NMDARs in a variety of neurological disorders; however, the function of NR2C/2D subunits at NAc in chronic pain remains unknown. In this study, spinal nerve ligation (SNL) induced a persistent sensory abnormity and depressive-like behavior. The whole-cell patch clamp recording on medium spiny neurons (MSNs) in the NAc showed that the amplitude of NMDAR-mediated excitatory postsynaptic currents (EPSCs) was significantly increased when membrane potential held at −40 to 0 mV in mice after 14 days of SNL operation. In addition, selective inhibition of NR2C/2D-containing NMDARs with PPDA caused a larger decrease on peak amplitude of NMDAR-EPSCs in SNL than that in sham-operated mice. Appling of selective potentiator of NR2C/2D, CIQ, markedly enhanced the evoked NMDAR-EPSCs in SNL-operated mice, but no change in sham-operated mice. Finally, intra-NAc injection of PPDA significantly attenuated SNL-induced mechanical allodynia and depressive-like behavior. These results for the first time showed that the functional change of NR2C/2D subunits-containing NMDARs in the NAc might contribute to the sensory and affective components in neuropathic pain.

【 授权许可】

Unknown