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Amyloid-beta pathology-induced nanoscale synaptic disruption:the case of the GABA_B-GIRK assembly

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Neural Regeneration Research 2025年第5期20卷 1409-1410页

作者： Rafael Lujan Alejandro Martín-Belmonte Sergi Ferré Francisco Ciruela Synaptic Structure Laboratory Instituto de Biomedicina de la UCLM(IB-UCLM)Departamento de Ciencias MédicasInstituto de Investigación en Salud de Castilla-La Mancha(IDISCAM)Facultad de MedicinaUniversidad Castilla-La ManchaCampus BiosanitarioC/AlmansaAlbaceteSpain Integrative Neurobiology Section National Institute on Drug AbuseIntramural Research ProgramNational Institutes of HealthBaltimoreMDUSA Pharmacology unit Department of Pathology and Experimental TherapeuticsSchool of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaNeuropharmacology&Pain GroupNeuroscience ProgramBellvitge Institute for Biomedical ResearchL’Hospitalet de LlobregatSpain

Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic *** has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.

关键词： Alzheimer pathology

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STING-ing pain:How Can Pro-inflammatory Signaling Attenuate pain?

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Neuroscience Bulletin 2021年第7期37卷 1075-1078页

作者： Wolfgang Liedtke Department of Neurology Duke University School of MedicineDurhamNC 27710USA Department of Anesthesiology Duke University School of MedicineDurhamNC 27710USA Department of Neurobiology Duke University School of MedicineDurhamNC 27710USA Duke Neurology Clinics for headache Head-Pain and Trigeminal Sensory DisordersDurhamNC 27705USA Clinics for Innovative pain Therapy Department of AnesthesiologyDuke UniversityRaleighNC 27512USA Chair of Neurology Global Scientific Development CouncilRegeneron PharmaceuticalsTarrytownNY 10591USA

Inflammation typically induces pain by producing pro-inflammatory mediators,but increasing evidence also indicates a role for inflammation in the resolution of pain by inducing anti-inflammatory and pro-resolution mediators[1,2].A recent Nature paper from Duke University,4pain behavioral metrics to uninjured mice and mice with nerve constriction injury or a rigorous model of bone cancer pain.

关键词： inflammatory interferon rigorous

Thalamocortical Circuit Controls Neuropathic pain via Up-regulation of HCN2 in the Ventral Posterolateral

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Neuroscience Bulletin 2023年第5期39卷 774-792页

作者： Yi Yan Mengye Zhu Xuezhong Cao Gang Xu Wei Shen Fan Li Jinjin Zhang Lingyun Luo Xuexue Zhang Daying Zhang Tao Liu Department of pain Medicine The First Affiliated Hospital of Nanchang UniversityNanchang 330006China Institute of pain Medicine Jiangxi Academy of Clinical and Medical SciencesNanchang 330006China Key Laboratory of Neuropathic pain Healthcare Commission of Jiangxi ProvinceNanchang 330006China Center for Experimental Medicine the First Affiliated Hospital of Nanchang UniversityNanchang 330006China

The thalamocortical(TC)circuit is closely asso-ciated with pain *** hyperpolarization-activated cyclic nucleotide-gated(HCN)2 channel is predominantly expressed in the ventral posterolateral thalamus(VPL)that has been shown to mediate neuropathic ***,the role of VPL HCN2 in modulating TC circuit activity is largely ***,by using optogenetics,neuronal trac-ing,electrophysiological recordings,and virus knockdown strategies,we showed that the activation of VPL TC neurons potentiates excitatory synaptic transmission to the hindlimb region of the primary somatosensory cortex(S1HL)as well as mechanical hypersensitivity following spared nerve injury(SNI)-induced neuropathic pain in *** pharmaco-logical blockade or virus knockdown of HCN2(shRNA-Hcn2)in the VPL was sufficient to alleviate SNI-induced ***,shRNA-Hcn2 decreased the excitability of TC neurons and synaptic transmission of the VPL-S1HL ***,our studies provide a novel mechanism by which HCN2 enhances the excitability of the TC circuit to facilitate neuropathic pain.

关键词： Neuropathic pain Thalamocortical circuit HCN2 channel Optogenetics Electrophysiology

Do neuronal microvascular activation and resultant dysfunction in rheumatoid arthritis contribute to chronic pain?

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Neural Regeneration Research 2019年第1期14卷 79-81页

作者： Nicholas Beazley-Long Arthritis Research UK pain Centre & School of Life Sciences Medical School University of Nottingham

Microvascular dysfunction and rheumatoid arthritis(RA):Across the UK severe osteoarthritis affects～5–7%and RA affects～1%of the *** are the most common causes of disabling chronic pain and are major burdens on individuals and ***,the annual financial cost to the UK economy for arthritis is in the billions of *** living with painful inflammatory conditions and

关键词：风湿性关节炎机能障碍疼痛激活骨关节炎心血管糖尿病 RA

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Cytochrome P45026A1 Contributes to the Maintenance of Neuropathic pain

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Neuroscience Bulletin 2024年第3期40卷 293-309页

作者： De-Li Cao Ling-Jie Ma Bao-Chun Jiang Qiang Gu Yong-Jing Gao Institute of pain Medicine and Special Environmental Medicine Co-innovation Center of NeuroregenerationNantong UniversityNantong226019China Nantong University Medical School Nantong226001China Department of pain Management The Affiliated Hospital of Nantong UniversityNantong226001China

The cytochrome P450 proteins(CYP450s)have been implicated in catalyzing numerous important biological reactions and contribute to a variety of ***26A1,a member of the CYP450 family,carries out the oxidative metabolism of retinoic acid(RA),the active metabolite of vitamin *** we report that CYP26A1 was dramatically upregulated in the spinal cord after spinal nerve ligation(SNL).CYP26A1 was mainly expressed in spinal neurons and *** analysis displayed that the content of all-trans-RA(at-RA),the substrate of CYP26A1,was reduced in the spinal cord on day 7 after *** of CYP26A1 by siRNA or inhibition of CYP26A1-mediated at-RA catabolism by talarozole relieved the SNL-induced mechanical allodynia during the maintenance phase of neuropathic *** also reduced SNL-induced glial activation and proinflammatory cytokine production but increased anti-inflammatory cytokine(IL-10)*** RA receptors RARα,RXRβ,and RXRγwere expressed in spinal neurons and glial *** promoter of Il-10 has several binding sites for RA receptors,and at-RA directly increased Il-10 mRNA expression in ***,intrathecal IL-10 attenuated SNL-induced neuropathic pain and reduced the activation of astrocytes and ***,the inhibition of CYP26A1-mediated at-RA catabolism alleviates SNL-induced neuropathic pain by promoting the expression of IL-10 and suppressing glial ***26A1 may be a potential therapeutic target for the treatment of neuropathic pain.

关键词： CYP26A1 Microglia Astrocytes ERK P38 IL-10 Neuropathic pain

Determination of vitamin D and analysis of risk factors for osteoporosis in patients with chronic pain

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World Journal of Clinical Cases 2020年第11期8卷 2150-2161页

作者： Bao-Lin Duan Yuan-Rong Mao Li-Qi Xue Qing-Yuan Yu Mei-Yi Liu Department of pain Qinghai Provincial People’s HospitalXining 810000Qinghai ProvinceChina

BACKGROUND Vitamin D deficiency is common in patients with chronic pain and healthy people,but the difference between the two has not been reported;thus,whether there is a relationship between vitamin D deficiency and chronic pain remains to be *** is a common disease in chronic pain *** the relationship between vitamin D and osteoporosis will provide a basis for the rational supplementation of vitamin D to prevent osteoporosis,and to understand the risk factors of bone mass change to provide a new treatment plan for early prevention of *** To determine 25 hydroxy vitamin D(25OHD)level in patients with chronic pain to clarify its clinical *** relationship between vitamin D and bone mineral density(BMD)and the risk factors for bone mass change were also *** In this study,184 patients with chronic pain were included in the study group,and 104 healthy individuals who underwent routine health checkups during the same period were included in the control group.25OHD level was detected in both groups by enzyme-linked immunosorbent *** to the BMD test results,the patients in the study group were further classified into three subgroups:Normal BMD group,reduced BMD group,and osteoporosis ***,sex,ethnicity,living altitude,body mass index,25OHD level,parathyroid hormone(PTH),calcium(Ca)and phosphorus levels were analyzed statistically in both *** The vitamin D level in the study group was lower than that in the control group at 53.8%vs 57.7%,with no significant difference between the two *** proportion of patients with severe vitamin D deficiency in the study group was higher than that in the control *** mean age was greater in the osteoporosis subgroup,and the youngest in the normal BMD *** D level in the osteoporosis subgroup was lower than that in the other two subgroups,and was not specific for the diagnosis of bone mass reduction and osteopo

关键词： Chronic pain Vitamin D deficiency Bone mass reduction Osteoporosis Bone mineral density

Management of lumbar zygapophysial (facet) joint pain

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World Journal of Orthopedics 2016年第5期7卷 315-337页

作者： Laxmaiah Manchikanti Joshua A Hirsch Frank JE Falco Mark V Boswell pain Management Center of Paducah Anesthesiology and Perioperative Medicine University of Louisville NeuroInterventional Services and Neuroen-dovascular Program Massachusetts General Hospital Harvard Medical School Mid Atlantic Spine and pain Physicians pain Medicine Fellowship Program Temple University Hospital

AIM: To investigate the diagnostic validity and therapeutic value of lumbar facet joint interventions in managing chronic low back ***: The review process applied systematic evidence-based assessment methodology of controlled trials of diagnostic validity and randomized controlled trials of therapeutic efficacy. Inclusion criteria encompassed all facet joint interventions performed in a controlled fashion. The pain relief of greater than 50% was the outcome measure for diagnostic accuracy assessment of the controlled studies with ability to perform previously painful movements, whereas, for randomized controlled therapeutic efficacy studies, the primary outcome was significant pain relief and the secondary outcome was a positive change in functional status. For the inclusion of the diagnostic controlled studies, all studies must have utilized either placebo controlled facet joint blocks or comparative local anesthetic blocks. In assessing therapeutic interventions, short-term and long-term reliefs were defined as either up to 6 mo or greater than 6 mo of relief. The literature search was extensive utilizing various types of electronic search media including Pub Med from 1966 onwards, Cochrane library, National Guideline Clearinghouse, ***, along with other sources includingprevious systematic reviews, non-indexed journals, and abstracts until March 2015. Each manuscript included in the assessment was assessed for methodologic quality or risk of bias assessment utilizing the Quality Appraisal of Reliability Studies checklist for diagnostic interventions, and Cochrane review criteria and the Interventional pain Management Techniques- Quality Appraisal of Reliability and Risk of Bias Assessment tool for therapeutic interventions. Evidence based on the review of the systematic assessment of controlled studies was graded utilizing a modified schema of qualitative evidence with best evidence synthesis, variable from level Ⅰ to level Ⅴ.RESULTS: Acro

关键词： Chronic low back pain Lumbar facet joint pain Lumbar discogenic pain Intraarticular injections Lumbar facet joint nerve blocks Lumbar facet joint radiofrequency Controlled diagnostic blocks Lumbar facet joint

Astrocytes in Chronic pain:Cellular and Molecular Mechanisms

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Neuroscience Bulletin 2023年第3期39卷 425-439页

作者： Huan-Jun Lu Yong-Jing Gao Institute of pain Medicine and Special Environmental Medicine Co-innovation Center of NeuroregenerationNantong UniversityNantong 226019China

Chronic pain is challenging to treat due to the limited therapeutic options and adverse side-effects of *** are the most abundant glial cells in the central nervous system and play important roles in different pathological conditions,including chronic *** regulate nociceptive synaptic transmission and network function via neuron–glia and glia–glia interactions to exaggerate pain signals under chronic pain *** is also becoming clear that astrocytes play active roles in brain regions important for the emotional and memory-related aspects of chronic ***,this review presents our current understanding of the roles of astrocytes in chronic pain,how they regulate nociceptive responses,and their cellular and molecular mechanisms of action.

关键词： Astrocyte Microglia Neuron-glia interaction Spinal cord Chronic pain

具有抗炎抗氧化作用的可注射壳聚糖微球用于缓解椎间盘退变（英文）

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Science China Materials 2025年

作者：黄林王挽涛刘磊马文政范景皓周丹赵磊郑召民刘洪梅吴德成 Guangdong Provincial Key Laboratory of Advanced Biomaterials Department of Biomedical Engineering Southern University of Science and Technology Department of Spine Surgery The First Affiliated Hospital Pain Research Center Sun Yat-sen University

由于椎间盘（IVD）特殊缺血性的组织结构,治疗椎间盘退变是一项巨大的挑战.椎间盘退变的治疗是一个复杂的过程,包括调节细胞炎症因子和氧化应力,恢复髓核细胞活性,并重建椎间盘生物力学功能.在此,我们构建了一种MnO2纳米酶和celecoxib...

由于椎间盘（IVD）特殊缺血性的组织结构,治疗椎间盘退变是一项巨大的挑战.椎间盘退变的治疗是一个复杂的过程,包括调节细胞炎症因子和氧化应力,恢复髓核细胞活性,并重建椎间盘生物力学功能.在此,我们构建了一种MnO2纳米酶和celecoxib药物胶束共同负载的可注射壳聚糖微球（CS-MnO2@PC）.体外细胞实验证明,这种复合微球具有较好的自由基清除、缓解细胞氧化应力、降低髓核细胞中炎症因子的表达等功能.体内实验进一步表明,该混合载体可以维持纤维环（AF）组织的板层结构和髓核（NP）组织的水合状态,这已通过影像学和组织切片学评估得以证实.这种纳米酶和药物胶束共同负载的可注射壳聚糖微球为治疗椎间盘退变提供了一种有效策略.

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