Locus Coeruleus Noradrenergic‐Spinal Projections Contribute to Electroacupuncture‐Mediated Antinociception in Postoperative Pain in Mice
Abstract Postoperative pain remains a significant challenge in healthcare. Electroacupuncture (EA) has gained polarity in helping manage surgical pain and showed beneficial effects on enhancing postoperative analgesia, decreasing opioid requirement. Despite this, the precise mechanisms underlying th...
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Wiley
2025-07-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202501182 |
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| author | Wen‐Guang Chu Ru Zhang Hai‐Tao Li Ying‐Chun Li Hui Ding Zhen‐Zhen Li Wen‐Juan Han Fei Wang Xing‐Xing Zheng Hong‐Hui Mao Hua Yuan Sheng‐Xi Wu Rou‐Gang Xie Ceng Luo |
| author_facet | Wen‐Guang Chu Ru Zhang Hai‐Tao Li Ying‐Chun Li Hui Ding Zhen‐Zhen Li Wen‐Juan Han Fei Wang Xing‐Xing Zheng Hong‐Hui Mao Hua Yuan Sheng‐Xi Wu Rou‐Gang Xie Ceng Luo |
| author_sort | Wen‐Guang Chu |
| collection | DOAJ |
| description | Abstract Postoperative pain remains a significant challenge in healthcare. Electroacupuncture (EA) has gained polarity in helping manage surgical pain and showed beneficial effects on enhancing postoperative analgesia, decreasing opioid requirement. Despite this, the precise mechanisms underlying these actions are poorly understood. Evidence shows the involvement of noradrenaline (NE) in the action of EA. However, the precise identity of the NE source after EA treatment, its mechanisms of action, and the circuitry locus in the pain‐regulating pathway remain elusive. It is shown that plantar incision (PI) leads to hypoactivity of noradrenergic neurons in the locus coeruleus (LC), which brings about impaired NE release in the spinal dorsal horn (SDH). EA treatment normalizes the abnormal hypoexcitability of LC noradrenergic neurons after PI and thus triggers enhanced NE release in the SDH. Optogenetic inhibition of LC noradrenergic neurons eliminates EA‐induced NE release and antinociceptive effects after PI, while activation of these neurons mimics EA‐induced NE release and antinociception. The resultant increased NE release after EA activates spinal α2A‐adrenoceptor and inhibits CaMKII signaling, which in turn depresses spinal excitatory neuronal hyperexcitability and eventually relieves postoperative pain. It is concluded that LC noradrenergic‐spinal projections and subsequent α2A‐adrenoceptor–CaMKII signaling cascades in the SDH contribute to EA‐induced antinociception in postoperative pain. |
| format | Article |
| id | doaj-art-a625d7ea86354b1b996d85217210c000 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
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| series | Advanced Science |
| spelling | doaj-art-a625d7ea86354b1b996d85217210c0002025-08-20T03:30:48ZengWileyAdvanced Science2198-38442025-07-011225n/an/a10.1002/advs.202501182Locus Coeruleus Noradrenergic‐Spinal Projections Contribute to Electroacupuncture‐Mediated Antinociception in Postoperative Pain in MiceWen‐Guang Chu0Ru Zhang1Hai‐Tao Li2Ying‐Chun Li3Hui Ding4Zhen‐Zhen Li5Wen‐Juan Han6Fei Wang7Xing‐Xing Zheng8Hong‐Hui Mao9Hua Yuan10Sheng‐Xi Wu11Rou‐Gang Xie12Ceng Luo13Department of Neurobiology School of Basic Medicine Fourth Military Medical University Xi'an 710032 ChinaDepartment of Neurobiology School of Basic Medicine Fourth Military Medical University Xi'an 710032 ChinaDepartment of Neurobiology School of Basic Medicine Fourth Military Medical University Xi'an 710032 ChinaDepartment of Neurobiology School of Basic Medicine Fourth Military Medical University Xi'an 710032 ChinaDepartment of Neurobiology School of Basic Medicine Fourth Military Medical University Xi'an 710032 ChinaDepartment of Neurobiology School of Basic Medicine Fourth Military Medical University Xi'an 710032 ChinaDepartment of Neurobiology School of Basic Medicine Fourth Military Medical University Xi'an 710032 ChinaDepartment of Neurobiology School of Basic Medicine Fourth Military Medical University Xi'an 710032 ChinaDepartment of Neurobiology School of Basic Medicine Fourth Military Medical University Xi'an 710032 ChinaDepartment of Neurobiology School of Basic Medicine Fourth Military Medical University Xi'an 710032 ChinaDepartment of Rehabilitation Medicine Xijing Hospital Fourth Military Medical University Xi'an 710032 ChinaDepartment of Neurobiology School of Basic Medicine Fourth Military Medical University Xi'an 710032 ChinaDepartment of Neurobiology School of Basic Medicine Fourth Military Medical University Xi'an 710032 ChinaDepartment of Neurobiology School of Basic Medicine Fourth Military Medical University Xi'an 710032 ChinaAbstract Postoperative pain remains a significant challenge in healthcare. Electroacupuncture (EA) has gained polarity in helping manage surgical pain and showed beneficial effects on enhancing postoperative analgesia, decreasing opioid requirement. Despite this, the precise mechanisms underlying these actions are poorly understood. Evidence shows the involvement of noradrenaline (NE) in the action of EA. However, the precise identity of the NE source after EA treatment, its mechanisms of action, and the circuitry locus in the pain‐regulating pathway remain elusive. It is shown that plantar incision (PI) leads to hypoactivity of noradrenergic neurons in the locus coeruleus (LC), which brings about impaired NE release in the spinal dorsal horn (SDH). EA treatment normalizes the abnormal hypoexcitability of LC noradrenergic neurons after PI and thus triggers enhanced NE release in the SDH. Optogenetic inhibition of LC noradrenergic neurons eliminates EA‐induced NE release and antinociceptive effects after PI, while activation of these neurons mimics EA‐induced NE release and antinociception. The resultant increased NE release after EA activates spinal α2A‐adrenoceptor and inhibits CaMKII signaling, which in turn depresses spinal excitatory neuronal hyperexcitability and eventually relieves postoperative pain. It is concluded that LC noradrenergic‐spinal projections and subsequent α2A‐adrenoceptor–CaMKII signaling cascades in the SDH contribute to EA‐induced antinociception in postoperative pain.https://doi.org/10.1002/advs.202501182electroacupuncturelocus coeruleusnoradrenalinepostoperative painST36 |
| spellingShingle | Wen‐Guang Chu Ru Zhang Hai‐Tao Li Ying‐Chun Li Hui Ding Zhen‐Zhen Li Wen‐Juan Han Fei Wang Xing‐Xing Zheng Hong‐Hui Mao Hua Yuan Sheng‐Xi Wu Rou‐Gang Xie Ceng Luo Locus Coeruleus Noradrenergic‐Spinal Projections Contribute to Electroacupuncture‐Mediated Antinociception in Postoperative Pain in Mice Advanced Science electroacupuncture locus coeruleus noradrenaline postoperative pain ST36 |
| title | Locus Coeruleus Noradrenergic‐Spinal Projections Contribute to Electroacupuncture‐Mediated Antinociception in Postoperative Pain in Mice |
| title_full | Locus Coeruleus Noradrenergic‐Spinal Projections Contribute to Electroacupuncture‐Mediated Antinociception in Postoperative Pain in Mice |
| title_fullStr | Locus Coeruleus Noradrenergic‐Spinal Projections Contribute to Electroacupuncture‐Mediated Antinociception in Postoperative Pain in Mice |
| title_full_unstemmed | Locus Coeruleus Noradrenergic‐Spinal Projections Contribute to Electroacupuncture‐Mediated Antinociception in Postoperative Pain in Mice |
| title_short | Locus Coeruleus Noradrenergic‐Spinal Projections Contribute to Electroacupuncture‐Mediated Antinociception in Postoperative Pain in Mice |
| title_sort | locus coeruleus noradrenergic spinal projections contribute to electroacupuncture mediated antinociception in postoperative pain in mice |
| topic | electroacupuncture locus coeruleus noradrenaline postoperative pain ST36 |
| url | https://doi.org/10.1002/advs.202501182 |
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