The role of N-methyl-D-aspartate receptor subunit NR2B in spinal cord in cancer pain.
Cancer pain is one kind of the most common and severe kinds of chronic pain. No breakthrough regarding the mechanisms and therapeutics of cancer pains has yet been achieved. Based on the well established involvement of the NMDA (N-methyl-D-aspartate) receptor containing NR2B in inflammatory pain and neuropathic pain and the effective pain relief obtained with ketamine in cancer patients with intractable pain, we supposed that NR2B in the spinal cord was an important factor for cancer pain. In this study, we investigated the possible role of NR2B in the spinal cord using a murine model of bone cancer pain. C3H/HeJ mice were inoculated into the intramedullary space of the right femur with Osteosarcoma NCTC 2472 cells to induce ongoing bone cancer-related pain behaviors. At day 14 after operation, the expression of NR2B mRNA and NR2B protein in the spinal cord were higher in tumor-bearing mice compared to the sham mice. Intrathecal administration of 5 and 10 microg of NR2B subunit-specific NMDA receptor antagonist ifenprodil attenuated cancer-evoked spontaneous pain, thermal hyperalgesia and mechanical allodynia. These results suggest that NR2B in the spinal cord may participate in bone cancer pain in mice, and ifenprodil may be a useful alternative or adjunct therapy for bone cancer pain. The findings may lead to novel strategies for the treatment of bone cancer pain.
Gu
XiaoPing
X
Department of Anesthesiology, Affiliated Drum-Tower Hospital of Medical College of Nanjing University, Nanjing, 210008 Jiangsu Province, China.
Zhang
Juan
J
Ma
ZhengLiang
Z
Wang
JunHua
J
Zhou
XiaoFang
X
Jin
YanQing
Y
Xia
XiaoPing
X
Gao
Qin
Q
Mei
FengMei
F
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001859:Bone Neoplasms / Q000150:complications* / Q000378:metabolism; D045744:Cell Line, Tumor / Q000637:transplantation; D002478:Cells, Cultured; D006930:Hyperalgesia / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D010146:Pain / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D011897:Random Allocation; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
C121001:NR2B NMDA receptor; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C010739:ifenprodil