As the most common symptomatic reason to seek medical consultation,pain is a complex experience that has been classified into different categories and stages.In pain processing,noxious stimuli may activate the anterio...As the most common symptomatic reason to seek medical consultation,pain is a complex experience that has been classified into different categories and stages.In pain processing,noxious stimuli may activate the anterior cingulate cortex(ACC).But the function of ACC in the different pain conditions is not well discussed.In this review,we elaborate the commonalities and differences from accumulated evidence by a variety of pain assays for physiological pain and pathological pain including inflammatory pain,neuropathic pain,and cancer pain in the ACC,and discuss the cellular receptors and signaling molecules from animal studies.We further summarize the ACC as a new central neuromodulation target for invasive and non-invasive stimulation techniques in clinical pain management.The comprehensive understanding of pain processing in the ACC may lead to bridging the gap in translational research between basic and clinical studies and to develop new therapies.展开更多
Central sensitization is essential in maintaining chronic pain induced by chronic pancreatitis(CP),but cortical modulation of painful CP remains elusive.Here,we examined the role of the anterior cingulate cortex(ACC)i...Central sensitization is essential in maintaining chronic pain induced by chronic pancreatitis(CP),but cortical modulation of painful CP remains elusive.Here,we examined the role of the anterior cingulate cortex(ACC)in the pathogenesis of abdominal hyperalgesia in a rat model of CP induced by intraductal administration of trinitrobenzene sulfonic acid(TNBS).TNBS treatment resulted in long-term abdominal hyperalgesia and anxiety in rats.Morphological data indicated that painful CP induced a significant increase in FOS-expressing neurons in the nucleus tractus solitarii(NTS)and ACC,and some FOS-expressing neurons in the NTS projected to the ACC.In addition,a larger portion of ascending fibers from the NTS innervated pyramidal neurons,the neural subpopulation primarily expressing FOS under the condition of painful CP,rather than GABAergic neurons within the ACC.CP rats showed increased expression of vesicular glutamate transporter 1,and increased membrane trafficking and phosphorylation of the N-methyl-D-aspartate receptor(NMDAR)subunit NR2B and theα-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor(AMPAR)subunit GluR1 within the ACC.Microinjection of NMDAR and AMPAR antagonists into the ACC to block excitatory synaptic transmission significantly attenuated abdominal hyperalgesia in CP rats,which was similar to the analgesic effect of endomorphins injected into the ACC.Specifically inhibiting the excitability of ACC pyramidal cells via chemogenetics reduced both hyperalgesia and comorbid anxiety,whereas activating these neurons via optogenetics failed to aggravate hyperalgesia and anxiety in CP rats.Taken together,these findings provide neurocircuit,biochemical,and behavioral evidence for involvement of the ACC in hyperalgesia and anxiety in CP rats,as well as novel insights into the cortical modulation of painful CP,and highlights the ACC as a potential target for neuromodulatory interventions in the treatment of painful CP.展开更多
Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairme...Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid neurotransmission.This review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain disorders.Improving understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these conditions.However,the mechanisms that regulate gamma-aminobutyric acidergic systems remain elusive.It is also unclear as to whether the mechanisms are presynaptic or postsynaptic.Further exploration of the complexities of this system may reveal new pathways for research and drug development.展开更多
In this study,we investigated how empathic neural responses unfold over time in different empathy networks when viewing same-race and other-race individuals in dynamic painful conditions.We recorded magnetoencephalogr...In this study,we investigated how empathic neural responses unfold over time in different empathy networks when viewing same-race and other-race individuals in dynamic painful conditions.We recorded magnetoencephalography signals from Chinese adults when viewing video clips showing a dynamic painful(or non-painful)stimulation to Asian and White models’faces to trigger painful(or neutral)expressions.We found that perceived dynamic pain in Asian models modulated neural activities in the visual cortex at 100 ms–200 ms,in the orbitofrontal and subgenual anterior cingulate cortices at 150 ms–200 ms,in the anterior cingulate cortex around 250 ms–350 ms,and in the temporoparietal junction and middle temporal gyrus around 600 ms after video onset.Perceived dynamic pain in White models modulated activities in the visual,anterior cingulate,and primary sensory cortices after 500 ms.Our findings unraveled earlier dynamic activities in multiple neural circuits in response to same-race(vs other-race)individuals in dynamic painful situations.展开更多
Objective To explore the role of the extracellular signal-regulated kinase （ERK）/cAMP response element binding protein （CREB） pathway in the induction of long-term potentiation （LTP） in the anterior cingulate co...Objective To explore the role of the extracellular signal-regulated kinase （ERK）/cAMP response element binding protein （CREB） pathway in the induction of long-term potentiation （LTP） in the anterior cingulate cortex （ACC） that may be implicated in pain-related negative emotion. Methods LTP of field potential was recorded in ACC slice and the expressions of phospho-ERK （pERK） and phospho-CREB （pCREB） were examined using immunohistochemistry method. Results LTP could be induced stably in ACC slice by high frequency stimulation （2-train, 100 Hz, 1 s）, while APv （an antagonist of NMDA receptor） could block the induction of LTP in the ACC, indicating that LTP in this experiment was NMDA receptor-dependent. Bath application of PD98059 （50 μmol/L）, a selective MEK inhibitor, at 30 min before tetanic stimulation could completely block the induction of LTP. Moreover, the protein level of pERK in the ACC was transiently increased after LTP induction, starting at 5 rain and returning to basal at 1 h after tetanic stimulation. The protein level of pCREB was also increased after LTP induction. The up-regulation in pERK and pCREB expressions could be blocked by pretreatment of PD98059. Double immunostaining showed that after LTP induction, most pERK was co-localized with pCREB. Conclusion NMDA receptor and ERK-CREB pathway are necessary for the induction of LTP in rat ACC and may play important roles in pain emotion.展开更多
Regional cerebral blood flow (rCBF) studies of major depression have yielded variable results. The present study employed a longitudinal observation method to measure rCBF every 3 months during treatment. Thirteen pat...Regional cerebral blood flow (rCBF) studies of major depression have yielded variable results. The present study employed a longitudinal observation method to measure rCBF every 3 months during treatment. Thirteen patients with major depressive disorder underwent single-photon emission computed tomography (SPECT) with 99mTc-HMPAO three times over a 6-month period. rCBF was analyzed with the Statistical Parametric Mapping. The findings were compared to scans from 14 normal control subjects. Depression symptoms were rated using the Hamilton Rating Scale for Depression. At baseline, the main regions with lower rCBF compared to controls were the middle and inferior frontal gyri, superior temporal gyrus, and cingulate cortex. Three months later, despite significant improvement of depressive symptoms, decreased rCBF was observed in the same regions, but to lesser extent. At 6 months, depressive symptoms showed continued improvement, and rCBF in the superior temporal gyrus increased up to control levels, but rCBF in the temporal pole, cingulate, and inferior frontal gyrus remained low. The results of the present study suggest that there might be time- and state-dependent differences in rCBF recovery in patients with major depression.展开更多
基金supported by the National Key R&D Program of China(2019YFA0709504)the National Natural Science Foundation of China(31930042,31771164,31900719,and 91630314)+6 种基金the Innovative Research Team of High-level Local Universities in ShanghaiDevelopment Project of Shanghai Peak Disciplines Integrated Chinese and Western MedicineShanghai Science and Technology Committee Rising-Star Program(19QA1401400)111 Project(B18015)Key Project of Shanghai Science&Technology(16JC1420402)Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJLab。
文摘As the most common symptomatic reason to seek medical consultation,pain is a complex experience that has been classified into different categories and stages.In pain processing,noxious stimuli may activate the anterior cingulate cortex(ACC).But the function of ACC in the different pain conditions is not well discussed.In this review,we elaborate the commonalities and differences from accumulated evidence by a variety of pain assays for physiological pain and pathological pain including inflammatory pain,neuropathic pain,and cancer pain in the ACC,and discuss the cellular receptors and signaling molecules from animal studies.We further summarize the ACC as a new central neuromodulation target for invasive and non-invasive stimulation techniques in clinical pain management.The comprehensive understanding of pain processing in the ACC may lead to bridging the gap in translational research between basic and clinical studies and to develop new therapies.
基金supported by the National Natural Science Foundations of China(81620108008 and 31971112)the Innovation Capability Support Program of Shaanxi Province,China(2021TD-57).
文摘Central sensitization is essential in maintaining chronic pain induced by chronic pancreatitis(CP),but cortical modulation of painful CP remains elusive.Here,we examined the role of the anterior cingulate cortex(ACC)in the pathogenesis of abdominal hyperalgesia in a rat model of CP induced by intraductal administration of trinitrobenzene sulfonic acid(TNBS).TNBS treatment resulted in long-term abdominal hyperalgesia and anxiety in rats.Morphological data indicated that painful CP induced a significant increase in FOS-expressing neurons in the nucleus tractus solitarii(NTS)and ACC,and some FOS-expressing neurons in the NTS projected to the ACC.In addition,a larger portion of ascending fibers from the NTS innervated pyramidal neurons,the neural subpopulation primarily expressing FOS under the condition of painful CP,rather than GABAergic neurons within the ACC.CP rats showed increased expression of vesicular glutamate transporter 1,and increased membrane trafficking and phosphorylation of the N-methyl-D-aspartate receptor(NMDAR)subunit NR2B and theα-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor(AMPAR)subunit GluR1 within the ACC.Microinjection of NMDAR and AMPAR antagonists into the ACC to block excitatory synaptic transmission significantly attenuated abdominal hyperalgesia in CP rats,which was similar to the analgesic effect of endomorphins injected into the ACC.Specifically inhibiting the excitability of ACC pyramidal cells via chemogenetics reduced both hyperalgesia and comorbid anxiety,whereas activating these neurons via optogenetics failed to aggravate hyperalgesia and anxiety in CP rats.Taken together,these findings provide neurocircuit,biochemical,and behavioral evidence for involvement of the ACC in hyperalgesia and anxiety in CP rats,as well as novel insights into the cortical modulation of painful CP,and highlights the ACC as a potential target for neuromodulatory interventions in the treatment of painful CP.
基金supported by the National Natural Science Foundation of China,Nos.82374561(to JD),82174490(to JF)the Medical and Health Science and Technology Program of Zhejiang Province,No.2021RC098(to JD)the Research Project of Zhejiang Chinese Medical University,Nos.2022JKZKTS44(to JD),2022FSYYZZ07(to JF).
文摘Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid neurotransmission.This review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain disorders.Improving understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these conditions.However,the mechanisms that regulate gamma-aminobutyric acidergic systems remain elusive.It is also unclear as to whether the mechanisms are presynaptic or postsynaptic.Further exploration of the complexities of this system may reveal new pathways for research and drug development.
基金supported by the National Natural Science Foundation of China(32230043)the Ministry of Science and Technology of China(2019YFA0707103)+1 种基金Das Chinesisch-Deutsche Zentrum fur Wissenschaftsforderung(M-0093)the High-performance Computing Platform of Peking University。
文摘In this study,we investigated how empathic neural responses unfold over time in different empathy networks when viewing same-race and other-race individuals in dynamic painful conditions.We recorded magnetoencephalography signals from Chinese adults when viewing video clips showing a dynamic painful(or non-painful)stimulation to Asian and White models’faces to trigger painful(or neutral)expressions.We found that perceived dynamic pain in Asian models modulated neural activities in the visual cortex at 100 ms–200 ms,in the orbitofrontal and subgenual anterior cingulate cortices at 150 ms–200 ms,in the anterior cingulate cortex around 250 ms–350 ms,and in the temporoparietal junction and middle temporal gyrus around 600 ms after video onset.Perceived dynamic pain in White models modulated activities in the visual,anterior cingulate,and primary sensory cortices after 500 ms.Our findings unraveled earlier dynamic activities in multiple neural circuits in response to same-race(vs other-race)individuals in dynamic painful situations.
基金supported by National Natural Science Fundation of China (No.30870835,30821002,and 30900444)National Basic Research Program of China (No. 2007CB512303,2007CB512502,and 2006CB500807)Postdoctoral Fundation of China (No.20080440578)
文摘Objective To explore the role of the extracellular signal-regulated kinase （ERK）/cAMP response element binding protein （CREB） pathway in the induction of long-term potentiation （LTP） in the anterior cingulate cortex （ACC） that may be implicated in pain-related negative emotion. Methods LTP of field potential was recorded in ACC slice and the expressions of phospho-ERK （pERK） and phospho-CREB （pCREB） were examined using immunohistochemistry method. Results LTP could be induced stably in ACC slice by high frequency stimulation （2-train, 100 Hz, 1 s）, while APv （an antagonist of NMDA receptor） could block the induction of LTP in the ACC, indicating that LTP in this experiment was NMDA receptor-dependent. Bath application of PD98059 （50 μmol/L）, a selective MEK inhibitor, at 30 min before tetanic stimulation could completely block the induction of LTP. Moreover, the protein level of pERK in the ACC was transiently increased after LTP induction, starting at 5 rain and returning to basal at 1 h after tetanic stimulation. The protein level of pCREB was also increased after LTP induction. The up-regulation in pERK and pCREB expressions could be blocked by pretreatment of PD98059. Double immunostaining showed that after LTP induction, most pERK was co-localized with pCREB. Conclusion NMDA receptor and ERK-CREB pathway are necessary for the induction of LTP in rat ACC and may play important roles in pain emotion.
文摘Regional cerebral blood flow (rCBF) studies of major depression have yielded variable results. The present study employed a longitudinal observation method to measure rCBF every 3 months during treatment. Thirteen patients with major depressive disorder underwent single-photon emission computed tomography (SPECT) with 99mTc-HMPAO three times over a 6-month period. rCBF was analyzed with the Statistical Parametric Mapping. The findings were compared to scans from 14 normal control subjects. Depression symptoms were rated using the Hamilton Rating Scale for Depression. At baseline, the main regions with lower rCBF compared to controls were the middle and inferior frontal gyri, superior temporal gyrus, and cingulate cortex. Three months later, despite significant improvement of depressive symptoms, decreased rCBF was observed in the same regions, but to lesser extent. At 6 months, depressive symptoms showed continued improvement, and rCBF in the superior temporal gyrus increased up to control levels, but rCBF in the temporal pole, cingulate, and inferior frontal gyrus remained low. The results of the present study suggest that there might be time- and state-dependent differences in rCBF recovery in patients with major depression.
