Pathophysiology‐Directed Engineering of a Combination Nanoanalgesic for Neuropathic Pain
Source abstract
Abstract
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.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Pain Mechanisms and Treatments · Neuropeptides and Animal Physiology · Nerve injury and regeneration
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Orthopedics Xinqiao Hospital Third Military Medical University (Army Medical University) Chongqing 400037 P. R. China
Department of Orthopedics General Hospital of PLA Xizang Military Area Command Lhasa 850007 P. R. China
Department of Pharmaceutics College of Pharmacy Third Military Medical University (Army Medical University) Chongqing 400038 P. R. China
War Trauma Medical Center State key Laboratory of Trauma Burns and Combined injury Army Medical Center Daping Hospital Third Military Medical University (Army Medical University) Chongqing 400038 P. R. China
Department of Orthopedics The Second Naval Hospital of Southern Theater Command Sanya 572000 P. R. China
School of Pharmacy Hanzhong Vocational and Technical College Hanzhong 723002 P. R. China
Department of General Surgery Xinqiao Hospital Third Military Medical University (Army Medical University) Chongqing 400037 P. R. China
Department of Orthopedics The First Affiliated Hospital Chongqing Medical University Chongqing 400016 P. R. China
State Key Laboratory of Trauma and Chemical Poisoning Third Military Medical University (Army Medical University) Chongqing 400038 P. R. China
Yu‐Yue Pathology Scientific Research Center 313 Gaoteng Avenue, Jiulongpo District Chongqing 400039 P. R. China
Funding
National Natural Science Foundation of China
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