Environmental enrichment alleviates neuropathic pain-associated anxiety by enhancing the function of parvalbumin interneurons in the anterior cingulate cortex
Abstract Chronic neuropathic pain is often accompanied with comorbid anxiety. However, effective interventions for this anxiety are highly limited. This study aims to examine the effect of environmental enrichment (EE) on spared nerve injury (SNI)-induced neuropathic pain-associated anxiety behavior...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-03-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-95220-6 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850063624358330368 |
|---|---|
| author | Zhuo-Yu Ren Bao-Yu Han Li-Yuan Zhao Xue-Jie Lou Yuan-Xiang Tao Guang-Fen Zhang Jian-Jun Yang |
| author_facet | Zhuo-Yu Ren Bao-Yu Han Li-Yuan Zhao Xue-Jie Lou Yuan-Xiang Tao Guang-Fen Zhang Jian-Jun Yang |
| author_sort | Zhuo-Yu Ren |
| collection | DOAJ |
| description | Abstract Chronic neuropathic pain is often accompanied with comorbid anxiety. However, effective interventions for this anxiety are highly limited. This study aims to examine the effect of environmental enrichment (EE) on spared nerve injury (SNI)-induced neuropathic pain-associated anxiety behaviors and explore the mechanisms underlying this effect. EE effectively ameliorated anxiety-like behaviors followed by SNI. EE also significantly reversed the phenotypic loss of parvalbumin (PV) interneurons in the anterior cingulate cortex (ACC) and impaired gamma oscillations under SNI-induced neuropathic pain conditions. In addition, EE reversed the SNI-induced reduction in the number of PV puncta around Ca²⁺/calmodulin-dependent protein kinase II-positive neurons. Furthermore, enhancing the function of PV interneurons could effectively improve the SNI-caused anxiety-like behaviors. In contrast, the inhibition of PV interneurons led to anxiety-like behaviors in naïve mice. Our findings suggest that EE significantly improves anxiety-like behaviors under neuropathic pain conditions, likely by enhancing the function of PV interneurons in ACC. |
| format | Article |
| id | doaj-art-6d1bb0962f4d4f5caafdef4c6590c5d7 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-6d1bb0962f4d4f5caafdef4c6590c5d72025-08-20T02:49:33ZengNature PortfolioScientific Reports2045-23222025-03-0115111510.1038/s41598-025-95220-6Environmental enrichment alleviates neuropathic pain-associated anxiety by enhancing the function of parvalbumin interneurons in the anterior cingulate cortexZhuo-Yu Ren0Bao-Yu Han1Li-Yuan Zhao2Xue-Jie Lou3Yuan-Xiang Tao4Guang-Fen Zhang5Jian-Jun Yang6Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New JerseyDepartment of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityDepartment of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou UniversityAbstract Chronic neuropathic pain is often accompanied with comorbid anxiety. However, effective interventions for this anxiety are highly limited. This study aims to examine the effect of environmental enrichment (EE) on spared nerve injury (SNI)-induced neuropathic pain-associated anxiety behaviors and explore the mechanisms underlying this effect. EE effectively ameliorated anxiety-like behaviors followed by SNI. EE also significantly reversed the phenotypic loss of parvalbumin (PV) interneurons in the anterior cingulate cortex (ACC) and impaired gamma oscillations under SNI-induced neuropathic pain conditions. In addition, EE reversed the SNI-induced reduction in the number of PV puncta around Ca²⁺/calmodulin-dependent protein kinase II-positive neurons. Furthermore, enhancing the function of PV interneurons could effectively improve the SNI-caused anxiety-like behaviors. In contrast, the inhibition of PV interneurons led to anxiety-like behaviors in naïve mice. Our findings suggest that EE significantly improves anxiety-like behaviors under neuropathic pain conditions, likely by enhancing the function of PV interneurons in ACC.https://doi.org/10.1038/s41598-025-95220-6Environmental enrichmentNeuropathic painPV interneuronsGamma Oscillation |
| spellingShingle | Zhuo-Yu Ren Bao-Yu Han Li-Yuan Zhao Xue-Jie Lou Yuan-Xiang Tao Guang-Fen Zhang Jian-Jun Yang Environmental enrichment alleviates neuropathic pain-associated anxiety by enhancing the function of parvalbumin interneurons in the anterior cingulate cortex Scientific Reports Environmental enrichment Neuropathic pain PV interneurons Gamma Oscillation |
| title | Environmental enrichment alleviates neuropathic pain-associated anxiety by enhancing the function of parvalbumin interneurons in the anterior cingulate cortex |
| title_full | Environmental enrichment alleviates neuropathic pain-associated anxiety by enhancing the function of parvalbumin interneurons in the anterior cingulate cortex |
| title_fullStr | Environmental enrichment alleviates neuropathic pain-associated anxiety by enhancing the function of parvalbumin interneurons in the anterior cingulate cortex |
| title_full_unstemmed | Environmental enrichment alleviates neuropathic pain-associated anxiety by enhancing the function of parvalbumin interneurons in the anterior cingulate cortex |
| title_short | Environmental enrichment alleviates neuropathic pain-associated anxiety by enhancing the function of parvalbumin interneurons in the anterior cingulate cortex |
| title_sort | environmental enrichment alleviates neuropathic pain associated anxiety by enhancing the function of parvalbumin interneurons in the anterior cingulate cortex |
| topic | Environmental enrichment Neuropathic pain PV interneurons Gamma Oscillation |
| url | https://doi.org/10.1038/s41598-025-95220-6 |
| work_keys_str_mv | AT zhuoyuren environmentalenrichmentalleviatesneuropathicpainassociatedanxietybyenhancingthefunctionofparvalbumininterneuronsintheanteriorcingulatecortex AT baoyuhan environmentalenrichmentalleviatesneuropathicpainassociatedanxietybyenhancingthefunctionofparvalbumininterneuronsintheanteriorcingulatecortex AT liyuanzhao environmentalenrichmentalleviatesneuropathicpainassociatedanxietybyenhancingthefunctionofparvalbumininterneuronsintheanteriorcingulatecortex AT xuejielou environmentalenrichmentalleviatesneuropathicpainassociatedanxietybyenhancingthefunctionofparvalbumininterneuronsintheanteriorcingulatecortex AT yuanxiangtao environmentalenrichmentalleviatesneuropathicpainassociatedanxietybyenhancingthefunctionofparvalbumininterneuronsintheanteriorcingulatecortex AT guangfenzhang environmentalenrichmentalleviatesneuropathicpainassociatedanxietybyenhancingthefunctionofparvalbumininterneuronsintheanteriorcingulatecortex AT jianjunyang environmentalenrichmentalleviatesneuropathicpainassociatedanxietybyenhancingthefunctionofparvalbumininterneuronsintheanteriorcingulatecortex |