Pathophysiology‐Directed Engineering of a Combination Nanoanalgesic for Neuropathic Pain
Abstract Neuropathic pain, one of the most refractory pain diseases, remains a formidable medical challenge. There is still an unmet demand for effective and safe therapies to address this condition. Herein, a rat model of nerve injury‐induced neuropathic pain is first established to explore its pat...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-02-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202405483 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850272438003171328 |
|---|---|
| author | Wenkai Wang Yan Wang Xinle Huang Peng Wu Lanlan Li Yang Zhang Yihui Chen Zhiyu Chen Changqing Li Yue Zhou Jianxiang Zhang |
| author_facet | Wenkai Wang Yan Wang Xinle Huang Peng Wu Lanlan Li Yang Zhang Yihui Chen Zhiyu Chen Changqing Li Yue Zhou Jianxiang Zhang |
| author_sort | Wenkai Wang |
| collection | DOAJ |
| description | Abstract Neuropathic pain, one of the most refractory pain diseases, remains a formidable medical challenge. There is still an unmet demand for effective and safe therapies to address this condition. Herein, a rat model of nerve injury‐induced neuropathic pain is first established to explore its pathophysiological characteristics. Recognizing the role of neuroinflammation, an inflammation‐resolving amphiphilic conjugate PPT is designed and synthesized by simultaneously conjugating polyethylene glycol, phenylboronic acid pinacol ester, and Tempol onto a cyclic scaffold. PPT can self‐assemble into nanomicelles (termed PPTN). Following intravenous injection, PPTN preferentially accumulates in the injured nerve, ameliorates the neuroinflammatory milieu, and promotes nerve regeneration, thereby shortening neuropathic pain duration in rats. Moreover, the Ca2+ channel α2δ1 subunit is identified as a therapeutic target by RNA‐sequencing analysis of the injured nerve. Based on this target, a mimicking peptide (AD peptide) is screened as an analgesic. By packaging AD peptide into PPTN, a combination nano‐analgesic APTN is developed. Besides potentiated anti‐hyperalgesic effects due to site‐specific delivery and on‐demand release of AD peptide at target sites, APTN simultaneously inhibits neuroinflammation and promotes nerve regeneration by reprogramming macrophages via regulating MAPK/NF‐kB signaling pathways and NLRP3 inflammasome activation, thus affording synergistic efficacies in treating nerve injury‐induced neuropathic pain. |
| format | Article |
| id | doaj-art-d3c9606345eb44da8b16935f50a1bad8 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-d3c9606345eb44da8b16935f50a1bad82025-08-20T01:51:48ZengWileyAdvanced Science2198-38442025-02-01128n/an/a10.1002/advs.202405483Pathophysiology‐Directed Engineering of a Combination Nanoanalgesic for Neuropathic PainWenkai Wang0Yan Wang1Xinle Huang2Peng Wu3Lanlan Li4Yang Zhang5Yihui Chen6Zhiyu Chen7Changqing Li8Yue Zhou9Jianxiang Zhang10Department of Orthopedics Xinqiao Hospital Third Military Medical University (Army Medical University) Chongqing 400037 P. R. ChinaDepartment of Pharmaceutics College of Pharmacy Third Military Medical University (Army Medical University) Chongqing 400038 P. R. ChinaDepartment of Orthopedics Xinqiao Hospital Third Military Medical University (Army Medical University) Chongqing 400037 P. R. ChinaDepartment of Pharmaceutics College of Pharmacy Third Military Medical University (Army Medical University) Chongqing 400038 P. R. ChinaDepartment of Pharmaceutics College of Pharmacy Third Military Medical University (Army Medical University) Chongqing 400038 P. R. ChinaDepartment of Orthopedics Xinqiao Hospital Third Military Medical University (Army Medical University) Chongqing 400037 P. R. ChinaDepartment of General Surgery Xinqiao Hospital Third Military Medical University (Army Medical University) Chongqing 400037 P. R. ChinaDepartment of Orthopedics The First Affiliated Hospital Chongqing Medical University Chongqing 400016 P. R. ChinaDepartment of Orthopedics Xinqiao Hospital Third Military Medical University (Army Medical University) Chongqing 400037 P. R. ChinaDepartment of Orthopedics Xinqiao Hospital Third Military Medical University (Army Medical University) Chongqing 400037 P. R. ChinaDepartment of Pharmaceutics College of Pharmacy Third Military Medical University (Army Medical University) Chongqing 400038 P. R. ChinaAbstract Neuropathic pain, one of the most refractory pain diseases, remains a formidable medical challenge. There is still an unmet demand for effective and safe therapies to address this condition. Herein, a rat model of nerve injury‐induced neuropathic pain is first established to explore its pathophysiological characteristics. Recognizing the role of neuroinflammation, an inflammation‐resolving amphiphilic conjugate PPT is designed and synthesized by simultaneously conjugating polyethylene glycol, phenylboronic acid pinacol ester, and Tempol onto a cyclic scaffold. PPT can self‐assemble into nanomicelles (termed PPTN). Following intravenous injection, PPTN preferentially accumulates in the injured nerve, ameliorates the neuroinflammatory milieu, and promotes nerve regeneration, thereby shortening neuropathic pain duration in rats. Moreover, the Ca2+ channel α2δ1 subunit is identified as a therapeutic target by RNA‐sequencing analysis of the injured nerve. Based on this target, a mimicking peptide (AD peptide) is screened as an analgesic. By packaging AD peptide into PPTN, a combination nano‐analgesic APTN is developed. Besides potentiated anti‐hyperalgesic effects due to site‐specific delivery and on‐demand release of AD peptide at target sites, APTN simultaneously inhibits neuroinflammation and promotes nerve regeneration by reprogramming macrophages via regulating MAPK/NF‐kB signaling pathways and NLRP3 inflammasome activation, thus affording synergistic efficacies in treating nerve injury‐induced neuropathic pain.https://doi.org/10.1002/advs.202405483nanoanalgesicnerve regenerationneuroinflammationneuropathic paintargeted therapy |
| spellingShingle | Wenkai Wang Yan Wang Xinle Huang Peng Wu Lanlan Li Yang Zhang Yihui Chen Zhiyu Chen Changqing Li Yue Zhou Jianxiang Zhang Pathophysiology‐Directed Engineering of a Combination Nanoanalgesic for Neuropathic Pain Advanced Science nanoanalgesic nerve regeneration neuroinflammation neuropathic pain targeted therapy |
| title | Pathophysiology‐Directed Engineering of a Combination Nanoanalgesic for Neuropathic Pain |
| title_full | Pathophysiology‐Directed Engineering of a Combination Nanoanalgesic for Neuropathic Pain |
| title_fullStr | Pathophysiology‐Directed Engineering of a Combination Nanoanalgesic for Neuropathic Pain |
| title_full_unstemmed | Pathophysiology‐Directed Engineering of a Combination Nanoanalgesic for Neuropathic Pain |
| title_short | Pathophysiology‐Directed Engineering of a Combination Nanoanalgesic for Neuropathic Pain |
| title_sort | pathophysiology directed engineering of a combination nanoanalgesic for neuropathic pain |
| topic | nanoanalgesic nerve regeneration neuroinflammation neuropathic pain targeted therapy |
| url | https://doi.org/10.1002/advs.202405483 |
| work_keys_str_mv | AT wenkaiwang pathophysiologydirectedengineeringofacombinationnanoanalgesicforneuropathicpain AT yanwang pathophysiologydirectedengineeringofacombinationnanoanalgesicforneuropathicpain AT xinlehuang pathophysiologydirectedengineeringofacombinationnanoanalgesicforneuropathicpain AT pengwu pathophysiologydirectedengineeringofacombinationnanoanalgesicforneuropathicpain AT lanlanli pathophysiologydirectedengineeringofacombinationnanoanalgesicforneuropathicpain AT yangzhang pathophysiologydirectedengineeringofacombinationnanoanalgesicforneuropathicpain AT yihuichen pathophysiologydirectedengineeringofacombinationnanoanalgesicforneuropathicpain AT zhiyuchen pathophysiologydirectedengineeringofacombinationnanoanalgesicforneuropathicpain AT changqingli pathophysiologydirectedengineeringofacombinationnanoanalgesicforneuropathicpain AT yuezhou pathophysiologydirectedengineeringofacombinationnanoanalgesicforneuropathicpain AT jianxiangzhang pathophysiologydirectedengineeringofacombinationnanoanalgesicforneuropathicpain |