Intrathecal STAT3 inhibitor Bt354 ameliorates chronic constriction injury-induced nociceptive sensitization by modulating neuroinflammation.
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| Natura: | Artículo científico |
| Lingua: | en |
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Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
2025
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| author | Cheng, Hao-Jung Chen, Nan-Fu Tang, Yueh-Chiao Shih, Po-Chang Chen, Wu-Fu Chiu, Ya-Jen Sung, Chun-Sung Wen, Zhi-Hong |
| author_facet | Cheng, Hao-Jung Chen, Nan-Fu Tang, Yueh-Chiao Shih, Po-Chang Chen, Wu-Fu Chiu, Ya-Jen Sung, Chun-Sung Wen, Zhi-Hong Cheng, Hao-Jung Chen, Nan-Fu Tang, Yueh-Chiao Shih, Po-Chang Chen, Wu-Fu Chiu, Ya-Jen Sung, Chun-Sung Wen, Zhi-Hong |
| collection | PubMed - marine biology |
| contents | Intrathecal STAT3 inhibitor Bt354 ameliorates chronic constriction injury-induced nociceptive sensitization by modulating neuroinflammation. Cheng, Hao-Jung Chen, Nan-Fu Tang, Yueh-Chiao Shih, Po-Chang Chen, Wu-Fu Chiu, Ya-Jen Sung, Chun-Sung Wen, Zhi-Hong Animals STAT3 Transcription Factor Male Rats Rats, Sprague-Dawley Injections, Spinal Neuralgia Neuroinflammatory Diseases Hyperalgesia Sciatic Nerve Neuropathic pain poses a significant societal and clinical burden and is closely linked to neuroinflammation of the central nervous system. Signal transducer and activator of transcription 3 (STAT3) is a key regulator of inflammatory processes and has been implicated in the development of nociceptive hypersensitivity. In this study, we aimed to elucidate the therapeutic potential and underlying mechanisms of STAT3 inhibition in a rodent model of neuropathic pain. Using behavioral assessments of nociceptive sensitivity and immunofluorescence analysis, we investigated the analgesic mechanisms of the intrathecal STAT3 inhibitor, Bt354, in rats subjected to chronic constriction injury (CCI) of the sciatic nerve. Cellular and molecular markers of glial activation and inflammation were examined to assess the effects of Bt354 on neuroinflammatory pathways. Intrathecal administration of Bt354 significantly reduced CCI-induced mechanical allodynia and thermal hyperalgesia, accompanied by a marked decrease in phosphorylated STAT3 (pSTAT3) expression in spinal neurons. Bt354 treatment attenuated the polarization of M1-type microglia and A1-type astrocytes, suppressed inflammasome-related signaling, and mitigated neuroinflammatory responses. Importantly, Bt354 inhibited the nuclear translocation of neuronal pSTAT3, which is a critical step in regulating pro-inflammatory gene transcription. Moreover, CCI-induced angiogenesis and microglial phosphorylation of CREB and P38 were mitigated by pSTAT3 inhibition. These findings suggest that STAT3 plays a central role in the pathogenesis of neuropathic pain by regulating glial cell polarization and neuroinflammation. Targeting STAT3 with Bt354 may represent a promising therapeutic strategy for treating neuropathic pain. |
| format | Artículo científico |
| id | pubmed_41067955 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics |
| record_format | pubmed |
| spellingShingle | Intrathecal STAT3 inhibitor Bt354 ameliorates chronic constriction injury-induced nociceptive sensitization by modulating neuroinflammation. Cheng, Hao-Jung Chen, Nan-Fu Tang, Yueh-Chiao Shih, Po-Chang Chen, Wu-Fu Chiu, Ya-Jen Sung, Chun-Sung Wen, Zhi-Hong Animals STAT3 Transcription Factor Male Rats Rats, Sprague-Dawley Injections, Spinal Neuralgia Neuroinflammatory Diseases Hyperalgesia Sciatic Nerve Intrathecal STAT3 inhibitor Bt354 ameliorates chronic constriction injury-induced nociceptive sensitization by modulating neuroinflammation. Cheng, Hao-Jung Chen, Nan-Fu Tang, Yueh-Chiao Shih, Po-Chang Chen, Wu-Fu Chiu, Ya-Jen Sung, Chun-Sung Wen, Zhi-Hong Animals STAT3 Transcription Factor Male Rats Rats, Sprague-Dawley Injections, Spinal Neuralgia Neuroinflammatory Diseases Hyperalgesia Sciatic Nerve Neuropathic pain poses a significant societal and clinical burden and is closely linked to neuroinflammation of the central nervous system. Signal transducer and activator of transcription 3 (STAT3) is a key regulator of inflammatory processes and has been implicated in the development of nociceptive hypersensitivity. In this study, we aimed to elucidate the therapeutic potential and underlying mechanisms of STAT3 inhibition in a rodent model of neuropathic pain. Using behavioral assessments of nociceptive sensitivity and immunofluorescence analysis, we investigated the analgesic mechanisms of the intrathecal STAT3 inhibitor, Bt354, in rats subjected to chronic constriction injury (CCI) of the sciatic nerve. Cellular and molecular markers of glial activation and inflammation were examined to assess the effects of Bt354 on neuroinflammatory pathways. Intrathecal administration of Bt354 significantly reduced CCI-induced mechanical allodynia and thermal hyperalgesia, accompanied by a marked decrease in phosphorylated STAT3 (pSTAT3) expression in spinal neurons. Bt354 treatment attenuated the polarization of M1-type microglia and A1-type astrocytes, suppressed inflammasome-related signaling, and mitigated neuroinflammatory responses. Importantly, Bt354 inhibited the nuclear translocation of neuronal pSTAT3, which is a critical step in regulating pro-inflammatory gene transcription. Moreover, CCI-induced angiogenesis and microglial phosphorylation of CREB and P38 were mitigated by pSTAT3 inhibition. These findings suggest that STAT3 plays a central role in the pathogenesis of neuropathic pain by regulating glial cell polarization and neuroinflammation. Targeting STAT3 with Bt354 may represent a promising therapeutic strategy for treating neuropathic pain. |
| title | Intrathecal STAT3 inhibitor Bt354 ameliorates chronic constriction injury-induced nociceptive sensitization by modulating neuroinflammation. |
| topic | Animals STAT3 Transcription Factor Male Rats Rats, Sprague-Dawley Injections, Spinal Neuralgia Neuroinflammatory Diseases Hyperalgesia Sciatic Nerve |
| url | https://pubmed.ncbi.nlm.nih.gov/41067955/ |