Mechanosensitive Ion Channel TMEM63A Gangs Up with Local Macrophages to Modulate Chronic Post-amputation Pain / 神经科学通报·英文版

Post-amputation pain causes great suffering to amputees, but still no effective drugs are available due to its elusive mechanisms. Our previous clinical studies found that surgical removal or radiofrequency treatment of the neuroma at the axotomized nerve stump effectively relieves the phantom pain afflicting patients after amputation. This 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 mystery. In this study, we found that nociceptors expressed the mechanosensitive ion channel TMEM63A and macrophages infiltrated into the dorsal root ganglion (DRG) neurons worked synergistically to promote CPAP. Histology 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 significantly 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 affected in the Tmem63a-/- mice in the naïve state, suggesting the basal pain was not affected. In the inflammatory and post-amputation state, the mechanical allodynia but not the heat hyperalgesia or cold allodynia was significantly decreased in Tmem63a-/- mice. Further study showed that there was severe neuronal injury and macrophage infiltration in the DRG, tibial nerve, residual stump, and the neuroma-like structure of the TNT mouse model, Consistent with this, expression of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β all increased dramatically in the DRG. Interestingly, the deletion of Tmem63a significantly reduced the macrophage infiltration in the DRG but not in the tibial nerve stump. Furthermore, the ablation of macrophages significantly reduced both the expression of Tmem63a and the mechanical allodynia in the TNT mouse model, indicating an interaction between nociceptors and macrophages, and that these two factors gang up together to regulate the formation of CPAP. This provides a new insight into the mechanisms underlying CPAP and potential drug targets its treatment.

Understanding of Appearance and Social Activities of Patients after Amputation: A 45 Cases Survey / 中国康复理论与实践

@# Objective To investigate the awareness of amputees to his appearance and their social activities. Methods 45 amputees were investigated with Body Shape Measuring for Amputee self-designed and Social Activities Questionnaire. Results For body shape measuring, the top 3 awareness amputees always feeling were: wearing loose clothing to cover the prosthesis (55.56%); only able-bodied can be attracted (48.89% ); losing of limbs damage the body and affect their daily living (40%). For the social activities, the total score was more in lower limb amputees than in upper limb amputees (P<0.05). For the items, there was no difference in amusement and sport, pastime, community participation, and join in workshop (school) (P>0.05) between the patient with upper and lower limbs losing, but there was in sociality (P<0.05). Conclusion Amputees fall in social withdrawal for limb losing and inferiority, which may associate with what limb lost.