title: Red nucleus glutamate facilitates neuropathic allodynia induced by spared nerve injury through non-NMDA and metabotropic glutamate receptors.
abstract: 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.
authors.affiliation: Department of Immunology and Pathogenic Biology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Immunology and Pathogenic Biology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Cui-Ping
authors.initials: CP
authors.lastname: Ding
authors.affiliation: Department of Immunology and Pathogenic Biology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Immunology and Pathogenic Biology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, People's Republic of China.|Department of Nuclear Medicine, Ankang City Center Hospital, Ankang, Shaanxi, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Immunology and Pathogenic Biology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, People's Republic of China.|Department of Nuclear Medicine, Ankang City Center Hospital, Ankang, Shaanxi, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Zeng
authors.affiliation: Department of Immunology and Pathogenic Biology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Jun-Yang
authors.initials: JY
authors.lastname: Wang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D018698:Glutamic Acid / Q000378:metabolism*; D006930:Hyperalgesia / Q000209:etiology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009437:Neuralgia / Q000150:complications* / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D012012:Red Nucleus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
chemical_list: D039481:CD11b Antigen; D018691:Excitatory Amino Acid Antagonists; D009419:Nerve Tissue Proteins; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid
keywords: N-methyl-D-aspartate receptor; RRID:AB_10711040; RRID:AB_2082593; RRID:AB_259946; RRID:AB_442947; RRID:AB_477010; RRID:nif-0000-30467; glutamate; metabotropic glutamate receptor; red nucleus; spared nerve injury