Lee, Jee Youn Park, Chan Sol Seo, Kyung Jin Kim, In Yi Han, Sungmin Youn, Inchan Yune, Tae Young 2024-01-12T06:31:46Z 2024-01-12T06:31:46Z 2023-10-23 2023-12 0014-4886 https://pubs.kist.re.kr/handle/201004/79716 After spinal cord injury (SCI), the control of activated glial cells such as microglia and astrocytes has emerged as a promising strategy for neuropathic pain management. However, signaling mechanism involved in glial activation in the process of neuropathic pain development and maintenance after SCI is not well elucidated. In this study, we investigated the potential role and mechanism of the JAK2/STAT3 pathway associated with glial cell activation in chronic neuropathic pain development and maintenance after SCI. One month after contusive SCI, the activation of JAK2/STAT3 pathway was markedly upregulated in both microglia and astrocyte in nociceptive processing regions of the lumbar spinal cord. In addition, both mechanical allodynia and thermal hyperalgesia was significantly inhibited by a JAK2 inhibitor, AG490. In particular, AG490 treatment inhibited both microglial and astrocyte activation in the lumbar (L) 4？5 dorsal horn and significantly decreased levels of p-p38MAPK, p-ERK and p-JNK, which are known to be activated in microglia (p-p38MAPK and p-ERK) and astrocyte (p-JNK). Experiments using primary cell cultures also revealed that the JAK2/STAT3 pathway promoted microglia and astrocyte activation after lipopolysaccharide stimulation. Furthermore, JAK2/STAT3 signaling and pain behaviors were significantly attenuated when the rats were treated with anti-IL-6 antibody. Finally, minocycline, a tetracycline antibiotic, inhibited IL-6/JAK2/STAT3 signaling pathway in activated glial cells and restored nociceptive thresholds and the hyperresponsiveness of dorsal neurons. These results suggest an important role of the IL-6/JAK2/STAT3 pathway in the activation of microglia and astrocytes and in the maintenance of chronic below-level pain after SCI. English Academic Press IL-6/JAK2/STAT3 axis mediates neuropathic pain by regulating astrocyte and microglia activation after spinal cord injury Article 10.1016/j.expneurol.2023.114576 1 Experimental Neurology, v.370 Experimental Neurology 370 N scie scopus 001096607400001 Neurosciences Neurosciences & Neurology Article MINOCYCLINE NEURONS INHIBITION INFLAMMATION MAINTENANCE TRANSDUCER EXPRESSION ROLES APOPTOTIC CELL-DEATH MECHANICAL ALLODYNIA Spinal cord injury JAK2/STAT3 pathway Central neuropathic pain minocycline glial activation