Transient peripheral compression induces persistent central pain: the acute constriction injury model
4 affiliations
- 1Department of Rehabilitation Therapy, School of Rehabilitation and Yunnan Key Laboratory of Plateau Thermal Medical Rehabilitation and Wellness, Kunming Medical University, Kunming, China
- 2Department of Rehabilitation, The First Affiliated Hospital of Kunming Medical University, Kunming, China
- 3Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen, China
- 4Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Tongji University School of Medicine, Shanghai, China
Abstract
Traditional neuropathic pain models such as chronic constriction injury (CCI) induce permanent peripheral nerve damage and cannot mimic persistent pain after resolved transient nerve compression. We established an acute constriction injury (ACI) model on male C57BL/6 J mice with 2-h sciatic nerve constriction followed by complete ligature removal, and performed a 250-day multimodal longitudinal comparison of Control, CCI and ACI mice using behavioral pain assays, somatosensory evoked potentials (SEPs), sciatic function index (SFI), nerve histology, muscle atrophy measurement, open field test, and serial 9.4 T pain-evoked BOLD-fMRI. ACI and CCI mice developed comparable long-lasting ipsilateral and delayed contralateral mechanical allodynia and thermal hyperalgesia over the 250-day observation period. Nonetheless, ACI mice achieved robust peripheral nerve structural and functional recovery without muscle atrophy, whereas CCI mice suffered irreversible peripheral nerve lesions. Serial fMRI revealed distinct brain activation trajectories: ACI mice exhibited spatially restricted response reductions relative to Controls and widespread suppression relative to CCI mice at day 3, isolated hypothalamic activation at day 12, and widespread bilateral activation of brainstem descending modulatory networks at day 250; in contrast, CCI mice showed cerebellar and somatosensory cortical activation at early/mid time points and significant deactivation of striatal-limbic circuits at late chronic stages. Anxiety-like behaviors were detected in both CCI and ACI mice at 12 day post-surgery but only in ACI mice at 7 months post-injury. These data support the pain centralization hypothesis: Brief peripheral nerve insult triggers self-maintained central sensitization that sustains chronic pain after peripheral anatomical and functional recovery. The ACI model may facilitate translational research on central-targeted therapeutics for compression-induced persistent neuropathic pain.
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BibTeX
@article{luo2026transient,
title = {{Transient peripheral compression induces persistent central pain: the acute constriction injury model}},
author = {Kaixuan Luo and Xiangjun Feng and Yang Liu and Guanchen Li and Yi Liu and Ping Yang and Yunuo Wang and Yu Sun and Moxian Chen and Shaochun Chen and Lijuan Ao and Lijuan Ao},
journal = {Frontiers in Systems Neuroscience},
year = {2026},
month = oct,
doi = {10.3389/fnsys.2026.1962461},
url = {https://doi.org/10.3389/fnsys.2026.1962461},
note = {CC BY},
}
RIS
TY - JOUR
TI - Transient peripheral compression induces persistent central pain: the acute constriction injury model
AU - Kaixuan Luo
AU - Xiangjun Feng
AU - Yang Liu
AU - Guanchen Li
AU - Yi Liu
AU - Ping Yang
AU - Yunuo Wang
AU - Yu Sun
AU - Moxian Chen
AU - Shaochun Chen
AU - Lijuan Ao
AU - Lijuan Ao
PY - 2026
DA - 2026/10/26
JO - Frontiers in Systems Neuroscience
DO - 10.3389/fnsys.2026.1962461
UR - https://doi.org/10.3389/fnsys.2026.1962461
AB - Traditional neuropathic pain models such as chronic constriction injury (CCI) induce permanent peripheral nerve damage and cannot mimic persistent pain after resolved transient nerve compression. We established an acute constriction injury (ACI) model on male C57BL/6 J mice with 2-h sciatic nerve constriction followed by complete ligature removal, and performed a 250-day multimodal longitudinal comparison of Control, CCI and ACI mice using behavioral pain assays, somatosensory evoked potentials (SEPs), sciatic function index (SFI), nerve histology, muscle atrophy measurement, open field test, and serial 9.4 T pain-evoked BOLD-fMRI. ACI and CCI mice developed comparable long-lasting ipsilateral and delayed contralateral mechanical allodynia and thermal hyperalgesia over the 250-day observation period. Nonetheless, ACI mice achieved robust peripheral nerve structural and functional recovery without muscle atrophy, whereas CCI mice suffered irreversible peripheral nerve lesions. Serial fMRI revealed distinct brain activation trajectories: ACI mice exhibited spatially restricted response reductions relative to Controls and widespread suppression relative to CCI mice at day 3, isolated hypothalamic activation at day 12, and widespread bilateral activation of brainstem descending modulatory networks at day 250; in contrast, CCI mice showed cerebellar and somatosensory cortical activation at early/mid time points and significant deactivation of striatal-limbic circuits at late chronic stages. Anxiety-like behaviors were detected in both CCI and ACI mice at 12 day post-surgery but only in ACI mice at 7 months post-injury. These data support the pain centralization hypothesis: Brief peripheral nerve insult triggers self-maintained central sensitization that sustains chronic pain after peripheral anatomical and functional recovery. The ACI model may facilitate translational research on central-targeted therapeutics for compression-induced persistent neuropathic pain.
SN - 1662-5137
ER -