Contribution of chemokine CCL2/CCR2 signaling in the dorsal root ganglion and spinal cord to the maintenance of neuropathic pain in a rat model of lumbar disc herniation.
Lumbar disc herniation (LDH) is a major cause of sciatica, but the underlying mechanisms are not well understood. Chemokine CCL2 has been implicated to play a vital role in the neuroinflammation and central sensitization after spinal nerve ligation. Here we investigated the expression and the role of CCL2 and its receptor CCR2 in LDH-induced pain. Implantation of autologous nucleus pulposus induced persistent pain hypersensitivity, associated with increased mRNA expression of CCL2 and CCR2 in the dorsal root ganglion and spinal cord. Interestingly, CCL2 was increased in neurons and CCR2 was mainly increased in macrophages in the dorsal root ganglion, whereas CCL2 and CCR2 were increased in astrocytes and neurons, respectively, in the spinal cord. Intrathecal injection of CCR2 antagonist RS504393 at 3 days or 10 days significantly attenuated nucleus pulposus-induced mechanical allodynia. The results suggest that CCL2/CCR2 in the dorsal root ganglion and spinal cord is involved in the maintenance of LDH-induced pain. Targeting CCL2/CCR2 signaling may be a potential treatment for chronic radicular neuropathic pain.


CONCLUSIONS
These results suggest that CCL2/CCR2 signaling in the dorsal root ganglion and spinal cord is involved in LDH-induced pain via distinct mechanisms. These findings provide evidence of the antinociceptive effect of CCR2 antagonist on radicular neuropathic pain.
Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, China; Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong, China.
Xiang
X
Zhu
Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, China.
Su
S
Cao
Pain Research Laboratory, Institute of Nautical Medicine, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China.
Ming-Di
MD
Zhu
Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong, China.
Jin-Qian
JQ
Liu
Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, China.
Jun-Jie
JJ
Chen
Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, China; Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong, China. Electronic address: gaoyongjing@hotmail.com.
Yong-Jing
YJ
Gao
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology; D048588:Benzoxazines / Q000494:pharmacology; D018932:Chemokine CCL2 / Q000378:metabolism*; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000187:drug effects / Q000503:physiopathology*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology; D007405:Intervertebral Disc Displacement / Q000503:physiopathology*; D008159:Lumbar Vertebrae; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008297:Male; D009437:Neuralgia / Q000188:drug therapy / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology*; D013141:Spiro Compounds / Q000494:pharmacology; D014110:Touch
D000700:Analgesics; D048588:Benzoxazines; C491766:Ccl2 protein, rat; C515336:Ccr2 protein, rat; D018932:Chemokine CCL2; D012333:RNA, Messenger; C579117:RS 504393; D054390:Receptors, CCR2; D013141:Spiro Compounds
Chemokines; astrocytes; chemokine C-C motif ligand 2 (CCL2); chemokine C-C motif receptor 2 (CCR2); lumber disc herniation; neuronal-glial interaction