Involvement of mediodorsal thalamus and its related neural circuit in pain regulation in mice
The mediodorsal thalamus (MD) constitutes an integral component of the medial nociceptive transmission system, although its precise role and related neural pathway in pain processing remains incompletely elucidated. While anatomical studies have confirm reciprocal projections between the MD and ante...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-10-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996125002724 |
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| author | Chu-han Liu Hui-jie Feng Fei Peng Shan Wang Liu-jie Zhao Hui Zhu Xue-ying Dou Ting Yuan Chuang Li Nan Zhou Wen-xin Zhang Xuan-ren Wang Yu-lin Dong |
| author_facet | Chu-han Liu Hui-jie Feng Fei Peng Shan Wang Liu-jie Zhao Hui Zhu Xue-ying Dou Ting Yuan Chuang Li Nan Zhou Wen-xin Zhang Xuan-ren Wang Yu-lin Dong |
| author_sort | Chu-han Liu |
| collection | DOAJ |
| description | The mediodorsal thalamus (MD) constitutes an integral component of the medial nociceptive transmission system, although its precise role and related neural pathway in pain processing remains incompletely elucidated. While anatomical studies have confirm reciprocal projections between the MD and anterior cingulate cortex (ACC), the functional contribution of ACC-MD neural circuitry to nociceptive regulation has not yet been systematically investigated. In this study, we used immunohistochemistry, pharmacogenetic manipulations, and multidimensional behavioral assessments to investigate the role of the MD and ACC-MD pathway in pain modulation. The MD can be activated by nociceptive stimuli, and mediates both exteroception-evoked reflexive-defensive reactions and interoception-mediated self-caring responses. Chemogenetics activation of the MD or the ACC-MD pathway induced hyperalgesia alongside aversion and anxiety-like behaviors. While inhibiting both alleviates pain and emotional comorbidities in neuropathic pain mice. These results identify a cortico-thalamic descending pathway that facilitates pain and emotional comorbidity, providing mechanistic insights for the developing neuromodulaion-based therapies against refractory neuropathic pain. |
| format | Article |
| id | doaj-art-37bd8c5c55d847f280af7f78b6a1908a |
| institution | Kabale University |
| issn | 1095-953X |
| language | English |
| publishDate | 2025-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj-art-37bd8c5c55d847f280af7f78b6a1908a2025-08-24T05:11:30ZengElsevierNeurobiology of Disease1095-953X2025-10-0121510705610.1016/j.nbd.2025.107056Involvement of mediodorsal thalamus and its related neural circuit in pain regulation in miceChu-han Liu0Hui-jie Feng1Fei Peng2Shan Wang3Liu-jie Zhao4Hui Zhu5Xue-ying Dou6Ting Yuan7Chuang Li8Nan Zhou9Wen-xin Zhang10Xuan-ren Wang11Yu-lin Dong12Department of Human Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an 710032, China; Innovation Researh Institute, Xijing Hopsital, The Fourth Military Medical University, Xi'an 710032, ChinaDepartment of Human Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an 710032, ChinaDepartment of Human Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an 710032, China; The Fifth Student Brigade of Basic Medical College, The Fourth Military Medical University, Xi'an 710032, ChinaDepartment of Human Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an 710032, China; Innovation Researh Institute, Xijing Hopsital, The Fourth Military Medical University, Xi'an 710032, ChinaDepartment of Human Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an 710032, China; Department of Anatomy, Basic Medical College, Zhengzhou University, Zhengzhou 450001, ChinaDepartment of Human Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an 710032, China; Department of Human Anatomy, School of Medical Science, Yan'an University, Yan'an, Shaanxi 716000, ChinaDepartment of Human Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an 710032, China; Department of Human Anatomy, School of Medical Science, Yan'an University, Yan'an, Shaanxi 716000, ChinaDepartment of Human Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an 710032, China; The First Cadets Brigade of Basic Medical College, The Fourth Military Medical University, Xi'an 710032, ChinaDepartment of Human Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an 710032, China; The First Cadets Brigade of Basic Medical College, The Fourth Military Medical University, Xi'an 710032, ChinaDepartment of Human Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an 710032, China; The Second Cadets Brigade of Basic Medical College, The Fourth Military Medical University, Xi'an 710032, ChinaDepartment of Human Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an 710032, China; The Second Cadets Brigade of Basic Medical College, The Fourth Military Medical University, Xi'an 710032, ChinaDepartment of Human Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an 710032, China; The Second Cadets Brigade of Basic Medical College, The Fourth Military Medical University, Xi'an 710032, ChinaDepartment of Human Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an 710032, China; Innovation Researh Institute, Xijing Hopsital, The Fourth Military Medical University, Xi'an 710032, China; Corresponding author at: Department of Human Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an 710032, China.The mediodorsal thalamus (MD) constitutes an integral component of the medial nociceptive transmission system, although its precise role and related neural pathway in pain processing remains incompletely elucidated. While anatomical studies have confirm reciprocal projections between the MD and anterior cingulate cortex (ACC), the functional contribution of ACC-MD neural circuitry to nociceptive regulation has not yet been systematically investigated. In this study, we used immunohistochemistry, pharmacogenetic manipulations, and multidimensional behavioral assessments to investigate the role of the MD and ACC-MD pathway in pain modulation. The MD can be activated by nociceptive stimuli, and mediates both exteroception-evoked reflexive-defensive reactions and interoception-mediated self-caring responses. Chemogenetics activation of the MD or the ACC-MD pathway induced hyperalgesia alongside aversion and anxiety-like behaviors. While inhibiting both alleviates pain and emotional comorbidities in neuropathic pain mice. These results identify a cortico-thalamic descending pathway that facilitates pain and emotional comorbidity, providing mechanistic insights for the developing neuromodulaion-based therapies against refractory neuropathic pain.http://www.sciencedirect.com/science/article/pii/S0969996125002724MDACCNeuropathic painEmotional comorbidityExteroceptionInteroception |
| spellingShingle | Chu-han Liu Hui-jie Feng Fei Peng Shan Wang Liu-jie Zhao Hui Zhu Xue-ying Dou Ting Yuan Chuang Li Nan Zhou Wen-xin Zhang Xuan-ren Wang Yu-lin Dong Involvement of mediodorsal thalamus and its related neural circuit in pain regulation in mice Neurobiology of Disease MD ACC Neuropathic pain Emotional comorbidity Exteroception Interoception |
| title | Involvement of mediodorsal thalamus and its related neural circuit in pain regulation in mice |
| title_full | Involvement of mediodorsal thalamus and its related neural circuit in pain regulation in mice |
| title_fullStr | Involvement of mediodorsal thalamus and its related neural circuit in pain regulation in mice |
| title_full_unstemmed | Involvement of mediodorsal thalamus and its related neural circuit in pain regulation in mice |
| title_short | Involvement of mediodorsal thalamus and its related neural circuit in pain regulation in mice |
| title_sort | involvement of mediodorsal thalamus and its related neural circuit in pain regulation in mice |
| topic | MD ACC Neuropathic pain Emotional comorbidity Exteroception Interoception |
| url | http://www.sciencedirect.com/science/article/pii/S0969996125002724 |
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