MHC-I promotes apoptosis of GABAergic interneurons in the spinal dorsal horn and contributes to cancer induced bone pain.
Cancer induced bone pain (CIBP) remains one of the most intractable clinical problems due to poor understanding of its underlying mechanisms. Recent studies demonstrate the decline of inhibitory interneurons, especially GABAergic interneurons in the spinal cord, can evoke generation of chronic pain. It has also been reported that neuronal MHC-I expression renders neurons vulnerable to cytotoxic CD8+T cells and finally lead to neurons apoptosis in a variety neurological disorders. However, whether MHC-I could induce the apoptosis of GABAergic interneurons in spinal cord and contribute to the development of CIBP remains unknown. In this study, we investigated roles of MHC-I and underlying mechanisms in CIBP on a rat model. Our results showed that increased MHC-I expression on GABAergic interneurons could deplete GABAergic interneurons by inducing their apoptosis in the spinal dorsal horn of tumor-bearing rats. Pretreatment of MHC-I RNAi-lentivirus could prevent the apoptosis of GABAergic interneurons and therefore alleviated mechanical allodynia induced by tumor cells intratibial injection. Additionally, we also found that CD8+T cells were colocalized with MHC-I and GABAergic neurons and presented a significant and persistent increase in the spinal cord of tumor-bearing rats. Taken together, these findings indicated that MHC-I could evoke CIBP by promoting apoptosis of GABAergic interneurons in the dorsal horn, and this apoptosis was closely related to local CD8+T cells.
Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Qiaochu
Q
Fu
Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Dai
D
Shi
Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Yaqun
Y
Zhou
Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Hua
H
Zheng
Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Hongbing
H
Xiang
Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Xuebi
X
Tian
Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Feng
F
Gao
School of Psychology, Social Work and Human Sciences, University of West London, London, UK.
Anne
A
Manyande
Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
Fei
F
Cao
Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: yktian@tjh.tjmu.edu.cn.
Yuke
Y
Tian
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: dy0711@gmail.com.
Dawei
D
Ye
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001859:Bone Neoplasms / Q000150:complications*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D000072716:Cancer Pain / Q000209:etiology* / Q000473:pathology*; D002277:Carcinoma / Q000150:complications*; D004195:Disease Models, Animal; D005260:Female; D059330:GABAergic Neurons / Q000187:drug effects / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D066148:Spinal Cord Dorsal Horn / Q000473:pathology*; D013997:Time Factors
D015395:Histocompatibility Antigens Class I; D034741:RNA, Small Interfering
CD8(+) T cells; Cancer induced bone pain; Disinhibition; GABAergic interneurons; MHC-I