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
| Autor: | Jun-Jie Chen, Yong-Jing Gao, Xiang Zhu, Ming-Di Zhu, Su Cao, Jin-Qian Liu |
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| Rok vydání: | 2014 |
| Předmět: |
Male
CCR2 Chemokine Pathology medicine.medical_specialty Hot Temperature Receptors CCR2 animal diseases Rats Sprague-Dawley Dorsal root ganglion Ganglia Spinal parasitic diseases medicine Animals Spiro Compounds RNA Messenger Chemokine CCL2 Neuroinflammation Neurons Sciatica Analgesics Lumbar Vertebrae biology business.industry Macrophages hemic and immune systems Spinal cord Benzoxazines Disease Models Animal Anesthesiology and Pain Medicine medicine.anatomical_structure Nociception Spinal Cord Neurology Hyperalgesia Touch Astrocytes Anesthesia Neuropathic pain biology.protein Neuralgia Neurology (clinical) medicine.symptom business Intervertebral Disc Displacement Signal Transduction |
| Zdroj: | The Journal of Pain. 15:516-526 |
| ISSN: | 1526-5900 |
| Popis: | 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. Perspective 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. |
| Databáze: | OpenAIRE |
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