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Mechanosensitive Ion Channel TMEM63A Gangs Up with Local Macrophages to Modulate Chronic post-amputation pain

Neuroscience Bulletin 2023年第2期39卷 177-193页

作者： Shaofeng Pu Yiyang Wu Fang Tong Wan-Jie Du Shuai Liu Huan Yang Chen Zhang Bin Zhou Ziyue Chen Xiaomeng Zhou Qingjian Han Dongping Du pain Management Center Shanghai Jiao Tong University Afliated Sixth People’s HospitalShanghai 200233China State Key Laboratory of Medical Neurobiology and MOE Frontier Center for Brain Science Institutes of Brain ScienceFudan UniversityShanghai 200032China

post-amputation pain causes great sufering to amputees,but still no efective drugs are available due to its elusive *** previous clinical studies found that surgical removal or radiofrequency treatment of the neuroma at the axotomized nerve stump efectively relieves the phantom pain aficting patients after *** indicated an essential role of the residual nerve stump in the formation of chronic post-amputation pain(CPAP).However,the molecular mechanism by which the residual nerve stump or neuroma is involved and regulates CPAP is still a *** this study,we found that nociceptors expressed the mechanosensitive ion channel TMEM63A and macrophages infltrated into the dorsal root ganglion(DRG)neurons worked synergistically to promote *** and qRT-PCR showed that TMEM63A was mainly expressed in mechanical pain-producing non-peptidergic nociceptors in the DRG,and the expression of TMEM63A increased signifcantly both in the neuroma from amputated patients and the DRG in a mouse model of tibial nerve transfer(TNT).Behavioral tests showed that the mechanical,heat,and cold sensitivity were not afected in the Tmem63a-/-mice in the naïve state,suggesting the basal pain was not *** the infammatory and post-amputation state,the mechanical allodynia but not the heat hyperalgesia or cold allodynia was signifcantly decreased in Tmem63a-/-*** study showed that there was severe neuronal injury and macrophage infltration in the DRG,tibial nerve,residual stump,and the neuromalike structure of the TNT mouse model,Consistent with this,expression of the pro-infammatory cytokines TNFα,IL-6,and IL-1βall increased dramatically in the ***,the deletion of Tmem63a signifcantly reduced the macrophage infltration in the DRG but not in the tibial nerve ***,the ablation of macrophages signifcantly reduced both the expression of Tmem63a and the mechanical allodynia in the TNT mouse model,indicating an interaction between

关键词： Mechanosensitive ion channel TMEM63A post-amputation pain Tibial nerve transfer Macrophage

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Lower extremity amputation:the emerging role of targeted muscle reinnervation(TMR)and regenerative peripheral nerve interface(RPNI)

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Plastic and Aesthetic Research 2022年第1期9卷 334-350页

作者： Yoshiko Toyoda Said Azoury Andrew Bauder L.Scott Levin Stephen Kovach Division of Plastic and Reconstructive Surgery University of PennsylvaniaPhiladelphiaPA 19104USA Department of Plastic and Reconstructive Surgery Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Department of Orthopedic Surgery University of PennsylvaniaPhiladelphiaPA 19104USA

Lower extremity amputation is increasingly prevalent in the United States,with growing numbers of patients suffering from diabetes and peripheral vascular *** has significant functional sequelae as more than half of patients are unable to ambulate at one year *** mobility and decreasing chronic post-amputation pain can significantly improve the quality of life for these patients and reduce the cost burden on the healthcare *** and reconstructive surgery has been at the forefront of“reconstructive amputation”,in which nerve pedicles can be surgically guided to decrease painful neuroma formation as well as provide targets for myoelectric prosthesis *** herein review post-amputation outcomes,epidemiology of chronic,post-amputation pain,and current treatments,including total muscle reinnervation and regenerative peripheral nerve interface,which are at the forefront of multidisciplinary treatment of lower extremity amputees.

关键词： Lower extremity amputation post-amputation pain neuroma targeted muscle reinnervation regenerative peripheral nerve interface

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