Persistent postsurgical pain is a major clinical concern,especially in the aging population,who represent a growing proportion of surgical patients.Although age is a known pain risk factor,the mechanisms driving age-r...Persistent postsurgical pain is a major clinical concern,especially in the aging population,who represent a growing proportion of surgical patients.Although age is a known pain risk factor,the mechanisms driving age-related vulnerability to chronic postoperative pain remain poorly understood.This study aims to investigate how aging influences the resolution of postoperative pain and to elucidate the roles of microglial activation and synaptic remodeling in the spinal dorsal horn.A plantar incision model in young(3-month-old)and aged(18-month-old)male and female mice was used to mimic postoperative pain conditions.Mechanical and thermal hypersensitivity at various postoperative intervals were assessed by von Frey and Hargreaves tests.Microglial activation and inhibitory/excitatory synaptic densities in the spinal dorsal horn were evaluated using immunofluorescence and 3D reconstruction with Imaris software.On postoperative day(POD)3,both age groups exhibited reduced pain thresholds on the ipsilateral side,along with microglial activation in the dorsal horn.On POD 7,pain thresholds in young mice had returned to baseline with no significant microglial activation,while aged mice showed sustained reduction in pain thresholds,continuous microglial activation,and significant loss of inhibitory synapses without detectable changes in excitatory synapse density.These findings are consistent across both sexes,with no sex-related differences.Collectively,these results suggest that aging is associated with persistent postoperative pain,which correlates with microglial activation and inhibitory synapse loss.These insights advance our understanding of age-related pain vulnerability and may inform the development of more effective,targeted,and age-specific therapeutic strategies to prevent or alleviate persistent postoperative pain in elderly patients.展开更多
Countries around the world have been making efforts to reduce pollutant emissions. However, the response of global black carbon(BC) aging to emission changes remains unclear. Using the Community Atmosphere Model versi...Countries around the world have been making efforts to reduce pollutant emissions. However, the response of global black carbon(BC) aging to emission changes remains unclear. Using the Community Atmosphere Model version 6 with a machine-learning-integrated four-mode version of the Modal Aerosol Module, we quantify global BC aging responses to emission reductions for 2011–2018 and for 2050 and 2100 under carbon neutrality. During 2011–18, global trends in BC aging degree(mass ratio of coatings to BC, R_(BC)) exhibited marked regional disparities, with a significant increase in China(5.4% yr^(-1)), which contrasts with minimal changes in the USA, Europe, and India. The divergence is attributed to opposing trends in secondary organic aerosol(SOA) and sulfate coatings, driven by regional changes in the emission ratios of corresponding coating precursors to BC(volatile organic compounds-VOCs/BC and SO_(2)/BC). Projections under carbon neutrality reveal that R_(BC) will increase globally by 47%(118%) in 2050(2100), with strong convergent increases expected across major source regions. The R_(BC) increase, primarily driven by enhanced SOA coatings due to sharper BC reductions relative to VOCs, will enhance the global BC mass absorption cross-section(MAC) by 11%(17%) in 2050(2100).Consequently, although the global BC burden will decline sharply by 60%(76%), the enhanced MAC partially offsets the magnitude of the decline in the BC direct radiative effect, resulting in the moderation of global BC DRE decreases to 88%(92%) of the BC burden reductions in 2050(2100). This study highlights the globally enhanced BC aging and light absorption capacity under carbon neutrality, thereby partly offsetting the impact of BC direct emission reductions on future changes in BC radiative effects globally.展开更多
基金supported by the National Natural Science Foundation of China(No.82401445 and 82271249)the China Postdoctoral Science Foundation(No.2024M752251)+3 种基金the Postdoctoral Fellowship Program of CPSF(No.GZC20241141)the Sichuan Science and Technology Program(No.2024NSFSC1636 and 2025ZNSFSC1645)the Postdoctoral Research Fund of West China Hospital of Sichuan University(No.2024HXBH013)1-3-5 Project for Disciplines of Excellence of West China Hospital of Sichuan University(No.ZYYC23002)。
文摘Persistent postsurgical pain is a major clinical concern,especially in the aging population,who represent a growing proportion of surgical patients.Although age is a known pain risk factor,the mechanisms driving age-related vulnerability to chronic postoperative pain remain poorly understood.This study aims to investigate how aging influences the resolution of postoperative pain and to elucidate the roles of microglial activation and synaptic remodeling in the spinal dorsal horn.A plantar incision model in young(3-month-old)and aged(18-month-old)male and female mice was used to mimic postoperative pain conditions.Mechanical and thermal hypersensitivity at various postoperative intervals were assessed by von Frey and Hargreaves tests.Microglial activation and inhibitory/excitatory synaptic densities in the spinal dorsal horn were evaluated using immunofluorescence and 3D reconstruction with Imaris software.On postoperative day(POD)3,both age groups exhibited reduced pain thresholds on the ipsilateral side,along with microglial activation in the dorsal horn.On POD 7,pain thresholds in young mice had returned to baseline with no significant microglial activation,while aged mice showed sustained reduction in pain thresholds,continuous microglial activation,and significant loss of inhibitory synapses without detectable changes in excitatory synapse density.These findings are consistent across both sexes,with no sex-related differences.Collectively,these results suggest that aging is associated with persistent postoperative pain,which correlates with microglial activation and inhibitory synapse loss.These insights advance our understanding of age-related pain vulnerability and may inform the development of more effective,targeted,and age-specific therapeutic strategies to prevent or alleviate persistent postoperative pain in elderly patients.
基金supported by the National Natural Science Foundation of China (42505149,41925023,U2342223,42105069,and 91744208)the China Postdoctoral Science Foundation (2025M770303)+1 种基金the Fundamental Research Funds for the Central Universities (14380230)the Jiangsu Funding Program for Excellent Postdoctoral Talent,and Jiangsu Collaborative Innovation Center of Climate Change。
文摘Countries around the world have been making efforts to reduce pollutant emissions. However, the response of global black carbon(BC) aging to emission changes remains unclear. Using the Community Atmosphere Model version 6 with a machine-learning-integrated four-mode version of the Modal Aerosol Module, we quantify global BC aging responses to emission reductions for 2011–2018 and for 2050 and 2100 under carbon neutrality. During 2011–18, global trends in BC aging degree(mass ratio of coatings to BC, R_(BC)) exhibited marked regional disparities, with a significant increase in China(5.4% yr^(-1)), which contrasts with minimal changes in the USA, Europe, and India. The divergence is attributed to opposing trends in secondary organic aerosol(SOA) and sulfate coatings, driven by regional changes in the emission ratios of corresponding coating precursors to BC(volatile organic compounds-VOCs/BC and SO_(2)/BC). Projections under carbon neutrality reveal that R_(BC) will increase globally by 47%(118%) in 2050(2100), with strong convergent increases expected across major source regions. The R_(BC) increase, primarily driven by enhanced SOA coatings due to sharper BC reductions relative to VOCs, will enhance the global BC mass absorption cross-section(MAC) by 11%(17%) in 2050(2100).Consequently, although the global BC burden will decline sharply by 60%(76%), the enhanced MAC partially offsets the magnitude of the decline in the BC direct radiative effect, resulting in the moderation of global BC DRE decreases to 88%(92%) of the BC burden reductions in 2050(2100). This study highlights the globally enhanced BC aging and light absorption capacity under carbon neutrality, thereby partly offsetting the impact of BC direct emission reductions on future changes in BC radiative effects globally.
