ag-490 and Neuralgia

ag-490 has been researched along with Neuralgia* in 2 studies

Other Studies

2 other study(ies) available for ag-490 and Neuralgia

ArticleYear
IL-6/JAK2/STAT3 axis mediates neuropathic pain by regulating astrocyte and microglia activation after spinal cord injury.
    Experimental neurology, 2023, Volume: 370

    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.

    Topics: Animals; Astrocytes; Hyperalgesia; Interleukin-6; Microglia; Neuralgia; Rats; Rats, Sprague-Dawley; Spinal Cord; Spinal Cord Dorsal Horn; Spinal Cord Injuries

2023
TC-2559, an α4β2 nicotinic acetylcholine receptor agonist, suppresses the expression of CCL3 and IL-1β through STAT3 inhibition in cultured murine macrophages.
    Journal of pharmacological sciences, 2015, Volume: 128, Issue:2

    The anti-inflammatory properties of TC-2559, an α4β2 nicotinic acetylcholine receptor (nAChR) agonist, on cultured murine macrophages was investigated. TC-2559 suppressed the upregulation of CC-chemokine ligand 3 (CCL3) and interleukin-1β (IL-1β) following lipopolysaccharide (LPS) treatment in J774A.1 cells. TC-2559 inhibited the phosphorylation of signal transducer and activator of transcription 3 (pSTAT3) but not nuclear factor-κB p65 after LPS. Blockade of pSTAT3 by AG490 inhibited the upregulation of CCL3 and IL-1β after LPS. In conclusion, TC-2559-driven α4β2 nAChR signaling suppressed the upregulation of CCL3 and IL-1β by inhibiting pSTAT3 in inflammatory macrophages, resulting in the suppression of neuropathic pain.

    Topics: Analgesics; Animals; Anti-Inflammatory Agents; Cells, Cultured; Chemokine CCL3; Gene Expression; Interleukin-1beta; Lipopolysaccharides; Macrophages; Mice; Neuralgia; Nicotinic Agonists; Phosphorylation; Pyridines; Receptors, Nicotinic; Signal Transduction; STAT3 Transcription Factor; Tyrphostins; Up-Regulation

2015
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