Many studies using diffusion tensor tractography（DTT） have demonstrated that injury of the spinothalamic tract（STT） is the pathogenetic mechanism of central post-stroke pain（CPSP） in intracerebral hemorrhage; ho...Many studies using diffusion tensor tractography（DTT） have demonstrated that injury of the spinothalamic tract（STT） is the pathogenetic mechanism of central post-stroke pain（CPSP） in intracerebral hemorrhage; however, there is no DTT study reporting the pathogenetic mechanism of CPSP in cerebral infarction. In this study, we investigated injury of the STT in patients with CPSP following cerebral infarction, using DTT. Five patients with CPSP following cerebral infarction and eight age-and sex-matched healthy control subjects were recruited for this study. STT was examined using DTT. Among DTT parameters of the affected STT, fractional anisotropy and tract volume were decreased by more than two standard deviations in two patients（patients 1 and 2） and three patients（patients 3, 4, and 5）, respectively, compared with those of the control subjects, while mean diffusivity value was increased by more than two standard deviations in one patient（patient 2）. Regarding DTT configuration, all affected STTs passed through adjacent part of the infarct and three STTs showed narrowing. These findings suggest that injury of the STT might be a pathogenetic etiology of CPSP in patients with cerebral infarction.展开更多
Thalamic hemorrhage can lead to the development of central post-stroke pain.Changes in histone acetylation levels,which are regulated by histone deacetylases,affect the excitability of neurons surrounding the hemorrha...Thalamic hemorrhage can lead to the development of central post-stroke pain.Changes in histone acetylation levels,which are regulated by histone deacetylases,affect the excitability of neurons surrounding the hemorrhagic area.However,the regulato ry mechanism of histone deacetylases in central post-stroke pain remains unclea r.Here,we show that iron overload leads to an increase in histone deacetylase 2expression in damaged ventral posterolateral nucleus neurons.Inhibiting this increase restored histone H3 acetylation in the Kcna2 promoter region of the voltage-dependent potassium(Kv)channel subunit gene in a rat model of central post-stroke pain,thereby increasing Kcna2expression and relieving central pain.However,in the absence of nerve injury,increasing histone deacetylase 2 expression decreased Kcna2expression,decreased Kv current,increased the excitability of neurons in the ventral posterolateral nucleus area,and led to neuropathic pain symptoms.Moreover,treatment with the iron chelator deferiprone effectively reduced iron overload in the ventral posterolateral nucleus after intracerebral hemorrhage,reversed histone deacetylase 2 upregulation and Kv1.2 downregulation,and alleviated mechanical hypersensitivity in central post-stroke pain rats.These results suggest that histone deacetylase 2 upregulation and Kv1.2 downregulation,mediated by iron overload,are important factors in central post-stroke pain pathogenesis and co uld se rve as new to rgets for central poststroke pain treatment.展开更多
The α2δ-1 subunit of the voltage-gated Ca2＋ channel （VGCC） is a molecular target of gabapentin （GBP）, which has been used as a first-line drug for the relief of neuropathic pain. GBP exerts its anti-nociceptive...The α2δ-1 subunit of the voltage-gated Ca2＋ channel （VGCC） is a molecular target of gabapentin （GBP）, which has been used as a first-line drug for the relief of neuropathic pain. GBP exerts its anti-nociceptive effects by disrupting trafficking of the α2δ-1 subunit to the presynaptic membrane, resulting in decreased neurotrans- mitter release. We previously showed that GBP has an anti- allodynic effect in the first two weeks; but this is followed by insensitivity in the later stage after repeated adminis- tration in a rat model of central post-stroke pain （CPSP） hypersensitivity induced by intra-thalamic hemorrhage. To explore the mechanisms underlying GBP insensitivity, the cellular localization and time-course of expression of the α2δ-1 subunit in both the thalamus and spinal dorsal horn were studied in the same model. We found that the α2δ-1 subunit was mostly localized in neurons, but not astrocytes and microglia. The level of α2δ-1 protein increased in the first two weeks after injury but then decreased in the third week, when GBP insensitivity occurred. Furthermore, the c^2g-1 down-regulation was likely caused by later neuronal loss in the injured thalamus through a mechanism other than apoptosis. In summary, the present results suggest that the GBP receptor ~2^-1 is mainly expressed in thalamic neurons in which it is up-regulated in the early stage of CPSP but this is followed by dramatic down-regulation, which is likely associated with GBP insensitivity after long-term use.展开更多
Phantom limb pain is a chronic pain syndrome that is difficult to cope with.Despite neurostimulation treatment is indicated for refractory neuropathic pain,there is scant evidence from randomized controlled trials to ...Phantom limb pain is a chronic pain syndrome that is difficult to cope with.Despite neurostimulation treatment is indicated for refractory neuropathic pain,there is scant evidence from randomized controlled trials to recommend it as the treatment choice.Thus,a systematic review was performed to analyze the efficacy of central nervous system stimulation therapies as a strategy for pain management in patients with phantom limb pain.A literature search for studies conducted between 1970 and September 2020 was carried out using the MEDLINE and Embase databases.Principles of The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline were followed.There were a total of 10 full-text articles retrieved and included in this review.Deep brain stimulation,repetitive transcranial magnetic stimulation,transcranial direct current stimulation,and motor cortex stimulation were the treatment strategies used in the selected clinical trials.Repetitive transcranial magnetic stimulation and transcranial direct current stimulation were effective therapies to reduce pain perception,as well as to relieve anxiety and depression symptoms in phantom limb pain patients.Conversely,invasive approaches were considered the last treatment option as evidence in deep brain stimulation and motor cortex stimulation suggests that the value of phantom limb pain treatment remains controversial.However,the findings on use of these treatment strategies in other forms of neuropathic pain suggest that these invasive approaches could be a potential option for phantom limb pain patients.展开更多
In this article, the mechanisms of central pain syndrome (CPS) are examined for the purpose of gaining insight into how a unified conscious experience arises from brain and body interaction. We provide a novel etiolog...In this article, the mechanisms of central pain syndrome (CPS) are examined for the purpose of gaining insight into how a unified conscious experience arises from brain and body interaction. We provide a novel etiology for CPS via implementation of the previously proposed 3D Default Space (3DDS) consciousness model in which consciousness and body schema arise when afferent information is processed by corticothalamic feedback loops and integrated via the thalamus. Further, we propose the mechanisms by which CPS represents deficits in dynamic interactions between afferent and efferent signaling. Modern hypotheses of CPS suggest roles for maladaptive neuroplasticity, a deafferentated somatosensory cortex and/or thalamus, and reorganization along the sensory pathways of the spinothalamic tract in the pathogenesis of the painful sensations. We propose that CPS arises when painful sensory signals originating along the maladapted and/or dysfunctional spinothalamic tract become accentuated by the dominant top down mechanisms of the brain.展开更多
Physical exe rcise effectively alleviates chronic pain associated with complex regional pain syndrome type-Ⅰ.However,the mechanism of exe rcise-induced analgesia has not been clarified.Recent studies have shown that ...Physical exe rcise effectively alleviates chronic pain associated with complex regional pain syndrome type-Ⅰ.However,the mechanism of exe rcise-induced analgesia has not been clarified.Recent studies have shown that the specialized pro-resolving lipid mediator resolvin E1 promotes relief of pathologic pain by binding to chemerin receptor 23 in the nervous system.However,whether the resolvin E1-chemerin receptor 23 axis is involved in exercise-induced analgesia in complex regional pain syndrome type-Ⅰ has not been demonstrated.In the present study,a mouse model of chronic post-ischemia pain was established to mimic complex regional pain syndrome type-Ⅰ and subjected to an intervention involving swimming at different intensities.Chronic pain was reduced only in mice that engaged in high-intensity swimming.The resolvin E1-chemerin receptor 23 axis was clearly downregulated in the spinal cord of mice with chronic pain,while high-intensity swimming restored expression of resolvin E1 and chemerin receptor 23.Finally,shRNA-mediated silencing of chemerin receptor 23in the spinal cord reve rsed the analgesic effect of high-intensity swimming exercise on chronic post-ischemic pain and the anti-inflammato ry pola rization of microglia in the dorsal horn of the spinal cord.These findings suggest that high-intensity swimming can decrease chronic pain via the endogenous resolvin E1-chemerin receptor 23 axis in the spinal cord.展开更多
Pain in Parkinson’s disease is common, with an estimated prevalence up to 85% of those with the disease. Central pain in Parkinson’s disease is poorly understood and the role of pharmacological treatment, including ...Pain in Parkinson’s disease is common, with an estimated prevalence up to 85% of those with the disease. Central pain in Parkinson’s disease is poorly understood and the role of pharmacological treatment, including the use of dopamine agonists, needs further investigation. Our objective is to discuss a case report of central pain in Parkinson’s disease in an outpatient setting. A 67-year-old-male patient with Parkinson’s disease presented with right-sided pain, which was refractory to non-steroidal anti-inflammatory drugs, acetaminophen, and opioid agonists. The initiation of dopaminergic therapy resulted in a near complete relief of pain. This case illustrates the need for a multidisciplinary approach to better care for Parkinson’s disease patients with central pain, and further study to identify the pathophysiologic mechanism.展开更多
基金supported by the National Research Foundation(NRF)of Korea Grant funded by the Korean Government(MSIP),No.NRF-2015R1D1A1A01060314
文摘Many studies using diffusion tensor tractography（DTT） have demonstrated that injury of the spinothalamic tract（STT） is the pathogenetic mechanism of central post-stroke pain（CPSP） in intracerebral hemorrhage; however, there is no DTT study reporting the pathogenetic mechanism of CPSP in cerebral infarction. In this study, we investigated injury of the STT in patients with CPSP following cerebral infarction, using DTT. Five patients with CPSP following cerebral infarction and eight age-and sex-matched healthy control subjects were recruited for this study. STT was examined using DTT. Among DTT parameters of the affected STT, fractional anisotropy and tract volume were decreased by more than two standard deviations in two patients（patients 1 and 2） and three patients（patients 3, 4, and 5）, respectively, compared with those of the control subjects, while mean diffusivity value was increased by more than two standard deviations in one patient（patient 2）. Regarding DTT configuration, all affected STTs passed through adjacent part of the infarct and three STTs showed narrowing. These findings suggest that injury of the STT might be a pathogenetic etiology of CPSP in patients with cerebral infarction.
基金supported by the National Natural Science Foundation of China,Nos.U2004106 (to WY),81971061 (to JC)the Key Scientific Research Project of Colleges and Universities in Henan Province,No.21A320039 (to WY)。
文摘Thalamic hemorrhage can lead to the development of central post-stroke pain.Changes in histone acetylation levels,which are regulated by histone deacetylases,affect the excitability of neurons surrounding the hemorrhagic area.However,the regulato ry mechanism of histone deacetylases in central post-stroke pain remains unclea r.Here,we show that iron overload leads to an increase in histone deacetylase 2expression in damaged ventral posterolateral nucleus neurons.Inhibiting this increase restored histone H3 acetylation in the Kcna2 promoter region of the voltage-dependent potassium(Kv)channel subunit gene in a rat model of central post-stroke pain,thereby increasing Kcna2expression and relieving central pain.However,in the absence of nerve injury,increasing histone deacetylase 2 expression decreased Kcna2expression,decreased Kv current,increased the excitability of neurons in the ventral posterolateral nucleus area,and led to neuropathic pain symptoms.Moreover,treatment with the iron chelator deferiprone effectively reduced iron overload in the ventral posterolateral nucleus after intracerebral hemorrhage,reversed histone deacetylase 2 upregulation and Kv1.2 downregulation,and alleviated mechanical hypersensitivity in central post-stroke pain rats.These results suggest that histone deacetylase 2 upregulation and Kv1.2 downregulation,mediated by iron overload,are important factors in central post-stroke pain pathogenesis and co uld se rve as new to rgets for central poststroke pain treatment.
基金supported by the National Natural Science Foundation of China(81171049)the National Basic Research Development Program of China(2011CB504100 and2013CB835100)+1 种基金the National Key Technology R&D Program of China(2013BAI04B04)the Twelfth Five-Year Project of China(AWS12J004)
文摘The α2δ-1 subunit of the voltage-gated Ca2＋ channel （VGCC） is a molecular target of gabapentin （GBP）, which has been used as a first-line drug for the relief of neuropathic pain. GBP exerts its anti-nociceptive effects by disrupting trafficking of the α2δ-1 subunit to the presynaptic membrane, resulting in decreased neurotrans- mitter release. We previously showed that GBP has an anti- allodynic effect in the first two weeks; but this is followed by insensitivity in the later stage after repeated adminis- tration in a rat model of central post-stroke pain （CPSP） hypersensitivity induced by intra-thalamic hemorrhage. To explore the mechanisms underlying GBP insensitivity, the cellular localization and time-course of expression of the α2δ-1 subunit in both the thalamus and spinal dorsal horn were studied in the same model. We found that the α2δ-1 subunit was mostly localized in neurons, but not astrocytes and microglia. The level of α2δ-1 protein increased in the first two weeks after injury but then decreased in the third week, when GBP insensitivity occurred. Furthermore, the c^2g-1 down-regulation was likely caused by later neuronal loss in the injured thalamus through a mechanism other than apoptosis. In summary, the present results suggest that the GBP receptor ~2^-1 is mainly expressed in thalamic neurons in which it is up-regulated in the early stage of CPSP but this is followed by dramatic down-regulation, which is likely associated with GBP insensitivity after long-term use.
文摘Phantom limb pain is a chronic pain syndrome that is difficult to cope with.Despite neurostimulation treatment is indicated for refractory neuropathic pain,there is scant evidence from randomized controlled trials to recommend it as the treatment choice.Thus,a systematic review was performed to analyze the efficacy of central nervous system stimulation therapies as a strategy for pain management in patients with phantom limb pain.A literature search for studies conducted between 1970 and September 2020 was carried out using the MEDLINE and Embase databases.Principles of The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline were followed.There were a total of 10 full-text articles retrieved and included in this review.Deep brain stimulation,repetitive transcranial magnetic stimulation,transcranial direct current stimulation,and motor cortex stimulation were the treatment strategies used in the selected clinical trials.Repetitive transcranial magnetic stimulation and transcranial direct current stimulation were effective therapies to reduce pain perception,as well as to relieve anxiety and depression symptoms in phantom limb pain patients.Conversely,invasive approaches were considered the last treatment option as evidence in deep brain stimulation and motor cortex stimulation suggests that the value of phantom limb pain treatment remains controversial.However,the findings on use of these treatment strategies in other forms of neuropathic pain suggest that these invasive approaches could be a potential option for phantom limb pain patients.
文摘In this article, the mechanisms of central pain syndrome (CPS) are examined for the purpose of gaining insight into how a unified conscious experience arises from brain and body interaction. We provide a novel etiology for CPS via implementation of the previously proposed 3D Default Space (3DDS) consciousness model in which consciousness and body schema arise when afferent information is processed by corticothalamic feedback loops and integrated via the thalamus. Further, we propose the mechanisms by which CPS represents deficits in dynamic interactions between afferent and efferent signaling. Modern hypotheses of CPS suggest roles for maladaptive neuroplasticity, a deafferentated somatosensory cortex and/or thalamus, and reorganization along the sensory pathways of the spinothalamic tract in the pathogenesis of the painful sensations. We propose that CPS arises when painful sensory signals originating along the maladapted and/or dysfunctional spinothalamic tract become accentuated by the dominant top down mechanisms of the brain.
基金National Key R&D Program of China,Nos.2019YFA0110300 (to LZ),2021YFA1201400 (to LZ)Natural Science Foundation of Shanghai,No.21ZR1468600 (to LZ)Open Fund of the Key Laboratory of Cellular Physiology (Shanxi Medical University),Ministry of Education,No.KLMEC/SXMU-201910 (to XJ)。
文摘Physical exe rcise effectively alleviates chronic pain associated with complex regional pain syndrome type-Ⅰ.However,the mechanism of exe rcise-induced analgesia has not been clarified.Recent studies have shown that the specialized pro-resolving lipid mediator resolvin E1 promotes relief of pathologic pain by binding to chemerin receptor 23 in the nervous system.However,whether the resolvin E1-chemerin receptor 23 axis is involved in exercise-induced analgesia in complex regional pain syndrome type-Ⅰ has not been demonstrated.In the present study,a mouse model of chronic post-ischemia pain was established to mimic complex regional pain syndrome type-Ⅰ and subjected to an intervention involving swimming at different intensities.Chronic pain was reduced only in mice that engaged in high-intensity swimming.The resolvin E1-chemerin receptor 23 axis was clearly downregulated in the spinal cord of mice with chronic pain,while high-intensity swimming restored expression of resolvin E1 and chemerin receptor 23.Finally,shRNA-mediated silencing of chemerin receptor 23in the spinal cord reve rsed the analgesic effect of high-intensity swimming exercise on chronic post-ischemic pain and the anti-inflammato ry pola rization of microglia in the dorsal horn of the spinal cord.These findings suggest that high-intensity swimming can decrease chronic pain via the endogenous resolvin E1-chemerin receptor 23 axis in the spinal cord.
文摘Pain in Parkinson’s disease is common, with an estimated prevalence up to 85% of those with the disease. Central pain in Parkinson’s disease is poorly understood and the role of pharmacological treatment, including the use of dopamine agonists, needs further investigation. Our objective is to discuss a case report of central pain in Parkinson’s disease in an outpatient setting. A 67-year-old-male patient with Parkinson’s disease presented with right-sided pain, which was refractory to non-steroidal anti-inflammatory drugs, acetaminophen, and opioid agonists. The initiation of dopaminergic therapy resulted in a near complete relief of pain. This case illustrates the need for a multidisciplinary approach to better care for Parkinson’s disease patients with central pain, and further study to identify the pathophysiologic mechanism.
