Analgesic effect of acupuncture is mediated via inhibition of JNK activation in astrocytes after spinal cord injury

• Published in: PloS one 2013-09, Vol.8 (9), p.e73948-e73948
• Main Authors: Lee, Jee Y, Choi, Doo C, Oh, Tae H, Yune, Tae Y
• Format: Article
• Language: English
• Subjects: Activation; Acupuncture; Acupuncture Therapy; Age; Analgesics; Anesthesia - methods; Animals; Astrocytes; Astrocytes - metabolism; Brain diseases; Brain research; c-Jun protein; Care and treatment; Chemokine CCL2 - genetics; Chemokine CCL2 - metabolism; Chemokine CCL20 - genetics; Chemokine CCL20 - metabolism; Chemokines; Cytokines; Dendritic cells; Dorsal horn; Enzyme Activation; Eutrophication; Gene Expression Regulation; Glial fibrillary acidic protein; Humidity; Hyperalgesia; Immunocytochemistry; Inhibitors; Injuries; JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors; JNK Mitogen-Activated Protein Kinases - metabolism; Kinases; Laminates; Macrophage Inflammatory Proteins - genetics; Macrophage Inflammatory Proteins - metabolism; Neuralgia; Neuralgia - etiology; Neuralgia - metabolism; Neuralgia - therapy; Neurodegeneration; Neuropathy; Neurosciences; Pain; Pain perception; Proteins; Proto-Oncogene Proteins c-jun - metabolism; Rats; Rheumatology; Rodents; Signal transduction; Spinal cord injuries; Spinal Cord Injuries - genetics; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - therapy; Transcription factors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0073948

Acupuncture (AP) has been used worldwide to relieve pain. However, the mechanism of action of AP is poorly understood. Here, we found that AP relieved neuropathic pain (NP) by inhibiting Jun-N-terminal kinase (JNK) activation in astrocytes after spinal cord injury (SCI). After contusion injury which induces the below-level (L4-L5) NP, Shuigou (GV26) and Yanglingquan (GB34) acupoints were applied. At 31 d after injury, both mechanical allodynia and thermal hyperalgesia were significantly alleviated by AP applied at GV26 and GB34. Immunocytochemistry revealed that JNK activation was mainly observed in astrocytes after injury. AP inhibited JNK activation in astrocytes at L4-L5 level of spinal cord. The level of p-c-Jun known, a downstream molecule of JNK, was also decreased by AP. In addition, SCI-induced GFAP expression, a marker for astrocytes, was decreased by AP as compared to control groups. Especially, the number of hypertrophic, activated astrocytes in laminae I-II of dorsal horn at L4-5 was markedly decreased by AP treatment when compared with vehicle and simulated AP-treated groups. When animals treated with SP600125, a specific JNK inhibitor, after SCI, both mechanical allodynia and thermal hyperalgesia were significantly attenuated by the inhibitor, suggesting that JNK activation is likely involved in SCI-induced NP. Also, the expression of chemokines which is known to be mediated through JNK pathway was significantly decreased by AP and SP600125 treatment. Therefore, our results indicate that analgesic effect of AP is mediated in part by inhibiting JNK activation in astrocytes after SCI.