Neuronal-derived Ccl7 drives neuropathic pain by promoting astrocyte proliferation.
Recent studies suggest that peripheral nerve injury converts resting spinal cord astroglial cells into an activated state, which is required for the development and maintenance of neuropathic pain. However, the underlying mechanisms of how resting astrocytes are activated after nerve injury remain largely unknown. Astroglial cell proliferation and activation could be affected by endogenous factors including chemokines, growth factors, and neurotropic factor. Chemokine (C-C motif) ligand 7 (Ccl7) is essential in facilitating the development of neuropathic pain; however, the mechanism is unknown. In the present study, we found that Ccl7 promoted astrocyte proliferation and thus contributed toward neuropathic pain. Spinal nerve ligation increased the expression in the spinal cord of neuronal Ccl7. Behavioral analyses showed that knockdown of Ccl7 alleviated spinal nerve ligation-induced neuropathic pain. Further in-vitro study showed that neuronal-derived Ccl7 was sufficient for the proliferation and activation of astroglial cells. We found a novel mechanism of Ccl7 stimulating the proliferation and activation of spinal cord astrocytes that contributes toward neuropathic pain.
aInstitute of Anesthesiology & pain (IAP), PET-CT and Department of Anesthesiology Departments of bNephrology cNeuroscience, Taihe Hospital, Hubei University of Medicine, Shiyan City, Hubei Province, China.
Bin Chang
BC
Ke
Xia Xiao
XX
Huang
Yang
Y
Li
Li Ya
LY
Li
Qin Xue
QX
Xu
Yan
Y
Gao
Yingju
Y
Liu
Jie
J
Luo
D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D054410:Chemokine CCL7 / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006930:Hyperalgesia / Q000503:physiopathology; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009437:Neuralgia / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism*; D017288:Pain Threshold / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation / Q000502:physiology
C515452:Ccl7 protein, rat; D054410:Chemokine CCL7; D005904:Glial Fibrillary Acidic Protein; D020929:Mitogen-Activated Protein Kinase Kinases