Red nucleus glutamate facilitates neuropathic allodynia induced by spared nerve injury through non-NMDA and metabotropic glutamate receptors.
Previous studies have demonstrated that glutamate plays an important role in the development of pathological pain. This study investigates the expression changes of glutamate and the roles of different types of glutamate receptors in the red nucleus (RN) in the development of neuropathic allodynia induced by spared nerve injury (SNI). Immunohistochemistry indicated that glutamate was constitutively expressed in the RN of normal rats. After SNI, the expression levels of glutamate were significantly increased in the RN at 1 week and reached the highest level at 2 weeks postinjury compared with sham-operated and normal rats. The RN glutamate was colocalized with neurons, oligodendrocytes, and astrocytes but not microglia under physiological and neuropathic pain conditions. To elucidate further the roles of the RN glutamate and different types of glutamate receptors in the development of neuropathic allodynia, antagonists to N-methyl-D-aspartate (NMDA), non-NMDA, or metabotropic glutamate receptors (mGluRs) were microinjected into the RN contralateral to the nerve-injury side of rats with SNI, and the paw withdrawal threshold (PWT) was dynamically assessed with von Frey filaments. Microinjection of the NMDA receptor antagonist MK-801 into the RN did not show any effect on SNI-induced mechanical allodynia. However, microinjection of the non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3(1H,4H)-dione or the mGluR antagonist (±)-α-methyl-(4-carboxyphenyl) glycine into the RN significantly increased the PWT and alleviated SNI-induced mechanical allodynia. These findings suggest that RN glutamate is involved in regulating neuropathic pain and facilitates the development of SNI-induced neuropathic allodynia. The algesic effect of glutamate is transmitted by the non-NMDA glutamate receptor and mGluRs.
['Yu|Jing|J|', 'Ding|Cui-Ping|CP|', 'Wang|Jing|J|', 'Wang|Ting|T|', 'Zhang|Tao|T|', 'Zeng|Xiao-Yan|XY|', 'Wang|Jun-Yang|JY|']
D000704:Analysis of Variance D000818:Animals D039481:CD11b Antigen D004195:Disease Models, Animal D018691:Excitatory Amino Acid Antagonists D018698:Glutamic Acid D006930:Hyperalgesia D008297:Male D009419:Nerve Tissue Proteins D009437:Neuralgia D009457:Neuroglia D009474:Neurons D010147:Pain Measurement D017288:Pain Threshold D051381:Rats D017207:Rats, Sprague-Dawley D018094:Receptors, Metabotropic Glutamate D012012:Red Nucleus
red nucleus glutamate spared nerve injury metabotropic glutamate receptor N-methyl-D-aspartate receptor RRID:AB_10711040 RRID:AB_2082593 RRID:AB_259946 RRID:AB_442947 RRID:AB_477010 RRID:nif-0000-30467