| Autor: |
Husain SF; Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228.; Biomedical Institute for Global Health Research and Technology, National University of Singapore, Singapore 117599., Lam RWM; Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228., Hu T; Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228.; Department of Spine Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China., Ng MWF; Singapore Bioimaging Consortium, Singapore 138667., Liau ZQG; Department of Orthopaedic Surgery, National University Hospital, National University Healthy System, Singapore 119228., Nagata K; Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228., Khanna S; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117593., Lam Y; Department of Chemistry, National University of Singapore, Singapore 117543., Bhakoo K; Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228.; Singapore Bioimaging Consortium, Singapore 138667., Ho RCM; Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228.; Biomedical Institute for Global Health Research and Technology, National University of Singapore, Singapore 117599.; Centre of Excellence in Behavioural Medicine, Nguyen Tat Thanh University, Ho Chi Minh City 70000, Vietnam.; Faculty of Education, Huaibei Normal University, Huaibei, Anhui 235000, China., Wong HK; Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228. |
| Abstrakt: |
Neuropathic pain remains underrecognised and ineffectively treated in chronic pain sufferers. Consequently, their quality of life is considerably reduced, and substantial healthcare costs are incurred. The anatomical location of pain must be identified for definitive diagnosis, but current neuropsychological tools cannot do so. Matrix metalloproteinases (MMP) are thought to maintain peripheral neuroinflammation, and MMP-12 is elevated particularly in such pathological conditions. Magnetic resonance imaging (MRI) of the peripheral nervous system has made headway, owing to its high-contrast resolution and multiplanar features. We sought to improve MRI specificity of neural lesions, by constructing an MMP-12-targeted magnetic iron oxide nanoparticle (IONP). Its in vivo efficiency was evaluated in a rodent model of neuropathic pain, where the left lumbar 5 (L5) spinal nerve was tightly ligated. Spinal nerve ligation (SNL) successfully induced mechanical allodynia, and thermal hyperalgesia, in the left hind paw throughout the study duration. These neuropathy characteristics were absent in animals that underwent sham surgery. MMP-12 upregulation with concomitant macrophage infiltration, demyelination, and elastin fibre loss was observed at the site of ligation. This was not observed in spinal nerves contralateral and ipsilateral to the ligated spinal nerve or uninjured left L5 spinal nerves. The synthesised MMP-12-targeted magnetic IONP was stable and nontoxic in vitro . It was administered onto the left L5 spinal nerve by intrathecal injection, and decreased magnetic resonance (MR) signal was observed at the site of ligation. Histology analysis confirmed the presence of iron in ligated spinal nerves, whereas iron was not detected in uninjured left L5 spinal nerves. Therefore, MMP-12 is a potential biomarker of neuropathic pain. Its detection in vivo , using IONP-enhanced MRI, may be further developed as a tool for neuropathic pain diagnosis and management. |
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