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What has brain diffusion magnetic resonance imaging taught us about chronic primary pain: a narrative review. 脑扩散磁共振成像教给我们的关于慢性原发性疼痛的知识:一个叙述性的回顾。
IF 5.9 1区 医学 Q1 ANESTHESIOLOGY Pub Date : 2025-02-01 Epub Date: 2024-08-21 DOI: 10.1097/j.pain.0000000000003345
Paul Bautin, Marc-Antoine Fortier, Monica Sean, Graham Little, Marylie Martel, Maxime Descoteaux, Guillaume Léonard, Pascal Tétreault

Abstract: Chronic pain is a pervasive and debilitating condition with increasing implications for public health, affecting millions of individuals worldwide. Despite its high prevalence, the underlying neural mechanisms and pathophysiology remain only partly understood. Since its introduction 35 years ago, brain diffusion magnetic resonance imaging (MRI) has emerged as a powerful tool to investigate changes in white matter microstructure and connectivity associated with chronic pain. This review synthesizes findings from 58 articles that constitute the current research landscape, covering methods and key discoveries. We discuss the evidence supporting the role of altered white matter microstructure and connectivity in chronic primary pain conditions, highlighting the importance of studying multiple chronic pain syndromes to identify common neurobiological pathways. We also explore the prospective clinical utility of diffusion MRI, such as its role in identifying diagnostic, prognostic, and therapeutic biomarkers. Furthermore, we address shortcomings and challenges associated with brain diffusion MRI in chronic primary pain studies, emphasizing the need for the harmonization of data acquisition and analysis methods. We conclude by highlighting emerging approaches and prospective avenues in the field that may provide new insights into the pathophysiology of chronic pain and potential new therapeutic targets. Because of the limited current body of research and unidentified targeted therapeutic strategies, we are forced to conclude that further research is required. However, we believe that brain diffusion MRI presents a promising opportunity for enhancing our understanding of chronic pain and improving clinical outcomes.

摘要:慢性疼痛是一种普遍的、使人衰弱的疾病,对公共卫生的影响越来越大,影响着全世界数百万人。尽管其发病率很高,但其潜在的神经机制和病理生理仍仅部分了解。自35年前推出以来,脑扩散磁共振成像(MRI)已成为研究与慢性疼痛相关的白质微观结构和连接变化的有力工具。这篇综述综合了58篇文章的发现,这些文章构成了当前的研究格局,涵盖了方法和关键发现。我们讨论了支持白质结构改变和连接在慢性原发性疼痛条件下的作用的证据,强调了研究多种慢性疼痛综合征以确定共同神经生物学途径的重要性。我们还探讨了弥散MRI的临床应用前景,如其在识别诊断、预后和治疗生物标志物方面的作用。此外,我们指出了脑弥散MRI在慢性原发性疼痛研究中的不足和挑战,强调了数据采集和分析方法统一的必要性。最后,我们强调了该领域的新兴方法和前瞻性途径,这些方法和途径可能为慢性疼痛的病理生理学和潜在的新治疗靶点提供新的见解。由于目前有限的研究和未确定的靶向治疗策略,我们不得不得出结论,需要进一步的研究。然而,我们相信脑扩散MRI为增强我们对慢性疼痛的理解和改善临床结果提供了一个有希望的机会。
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引用次数: 0
Where do we start? Health care transition in adolescents and young adults with chronic primary pain. 我们从哪里开始?患有慢性原发性疼痛的青少年的医疗过渡。
IF 5.9 1区 医学 Q1 ANESTHESIOLOGY Pub Date : 2025-02-01 Epub Date: 2024-07-09 DOI: 10.1097/j.pain.0000000000003324
Amanda B Feinstein, Kimberly Brown, Ashley L Dunn, Alexandra J Neville, Olivia Sokol, Heather Poupore-King, John A Sturgeon, Albert H Kwon, Anya T Griffin
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引用次数: 0
Education, gender, and frequent pain among middle-aged and older adults in the United States, England, China, and India. 美国、英国、中国和印度中老年人的教育、性别和经常性疼痛。
IF 5.9 1区 医学 Q1 ANESTHESIOLOGY Pub Date : 2025-02-01 Epub Date: 2024-08-26 DOI: 10.1097/j.pain.0000000000003349
Chihua Li, Chunyu Liu, Chenfei Ye, Zi Lian, Peiyi Lu

Abstract: Using cross-sectional data from the United States, England, China, and India, we examined the relationship between education and frequent pain, alongside the modification role of gender in this relationship. We further examined patterns of 3 pain dimensions among participants who reported frequent pain, including pain severity, interference with daily activities, and medication use (these pain dimension questions were not administered in all countries). Our analytical sample included 92,204 participants aged 50 years and above. We found a high prevalence of frequent pain across the 4 countries ranging from 28% to 41%. Probit models showed that higher education was associated with lower risk of pain (United States: -0.26, 95% CI: -0.33, -0.19; England: -0.32, 95% CI: -0.39, -0.25; China: -0.33, 95% CI -0.41, -0.26; India: -0.18, 95% CI -0.21, -0.15). Notably, in China and India, the negative association between higher education and frequent pain was less pronounced among women compared with men, which was not observed in the United States or England. Further analysis showed that individuals with higher education experiencing frequent pain reported less severity, fewer daily activity interferences, and less medication use compared with those with lower education. In the United States, these associations were stronger among women. Our findings highlight the prevalent pain among middle-aged and older adults in these 4 countries and emphasize the potentially protective role of higher education on frequent pain, with nuanced gender differences across different settings. This underscores the need for tailored strategies considering educational and gender differences to improve pain management and awareness.

摘要:利用来自美国、英国、中国和印度的横截面数据,我们研究了教育程度与经常疼痛之间的关系,以及性别在这种关系中的调节作用。我们还进一步研究了报告经常疼痛的参与者的三个疼痛维度的模式,包括疼痛严重程度、对日常活动的干扰和药物使用(这些疼痛维度的问题并非在所有国家都有提供)。我们的分析样本包括 92 204 名 50 岁及以上的参与者。我们发现,在 4 个国家中,经常疼痛的发生率很高,从 28% 到 41% 不等。Probit 模型显示,教育程度越高,疼痛风险越低(美国:-0.26,95% C%-0.26):美国:-0.26,95% CI:-0.33,-0.19;英国:-0.32,95% CI:-0.39,-0.25;中国:-0.33,95% CI:-0.41,-0.26;印度:-0.18,95% CI:-0.21,-0.15)。值得注意的是,在中国和印度,与男性相比,受过高等教育的女性与经常性疼痛之间的负相关关系不那么明显,而这一点在美国和英国没有观察到。进一步的分析表明,与受教育程度较低的人相比,受教育程度较高、经常感到疼痛的人所报告的疼痛严重程度较轻,日常活动受到的干扰较少,用药也较少。在美国,这些关联在女性中更为明显。我们的研究结果突显了这 4 个国家中老年人疼痛的普遍性,并强调了高等教育对经常性疼痛的潜在保护作用,不同环境下的性别差异也有细微差别。这突出表明,有必要考虑教育和性别差异,制定有针对性的策略,以改善疼痛管理和提高对疼痛的认识。
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引用次数: 0
Treatment mechanism and outcome decoupling effects in cognitive therapy, mindfulness-based stress reduction, and behavior therapy for chronic pain. 认知疗法、正念减压疗法和慢性疼痛行为疗法的治疗机制和结果脱钩效应。
IF 5.9 1区 医学 Q1 ANESTHESIOLOGY Pub Date : 2025-02-01 Epub Date: 2024-08-30 DOI: 10.1097/j.pain.0000000000003374
James Gerhart, John W Burns, Beverly Thorn, Mark Jensen, James Carmody, Francis Keefe

Abstract: Findings suggest that cognitive therapy (CT), mindfulness-based stress reduction (MBSR), and behavior therapy (BT) for chronic pain produce improvements through changes in putative mechanisms. Evidence supporting this notion is largely based on findings showing significant associations between treatment mechanism variables and outcomes. An alternative view is that treatments may work by reducing or decoupling the impact of changes in mechanism variables on changes in outcomes. We examined the degree to which relationships between previous changes in potential treatment mechanisms and subsequent changes in outcomes changed as treatment progressed and vice versa. Cognitive therapy, MBSR, BT, and treatment as usual (TAU) were compared in people with chronic low back pain (N = 521). Eight individual sessions were administered with weekly assessments of putative treatment mechanisms and outcomes. Lagged analyses revealed mechanism × session number interactions and outcome × session number interactions, such that associations between mechanism and outcome variables were strong and significant in the first third of treatment, but weakened over time and became nonsignificant by the last third of treatment. These effects were similar across treatment conditions but did not emerge among people undergoing TAU. Results suggest that during the course of CT, MBSR, and BT, the links between changes in treatment mechanism variables became decoupled from subsequent changes in outcomes and vice versa. Thus, starting by midtreatment and continuing into late treatment, participants may have learned through participation in the treatments that episodes of maladaptive pain-related thoughts and/or spikes in pain need not have detrimental consequences on their subsequent experience.

摘要:研究结果表明,认知疗法(CT)、正念减压疗法(MBSR)和行为疗法(BT)通过改变假定机制来改善慢性疼痛。支持这一观点的证据主要基于治疗机制变量与治疗结果之间存在显著关联的研究结果。另一种观点认为,治疗方法可能通过减少或解除机制变量变化对结果变化的影响而发挥作用。我们研究了潜在治疗机制的先前变化与后续结果变化之间的关系随治疗进展而变化的程度,反之亦然。我们对慢性腰背痛患者(521 人)的认知疗法、MBSR、BT 和常规治疗(TAU)进行了比较。共进行了八次单独治疗,每周对假定的治疗机制和结果进行评估。滞后分析显示了机制×疗程数交互作用和结果×疗程数交互作用,因此机制和结果变量之间的关联在治疗的前三分之一时间内是强烈和显著的,但随着时间的推移逐渐减弱,到治疗的最后三分之一时间变得不显著。这些效应在不同的治疗条件下相似,但在接受 TAU 治疗的人群中没有出现。结果表明,在 CT、MBSR 和 BT 治疗过程中,治疗机制变量的变化与后续结果变化之间的联系变得不相关,反之亦然。因此,从治疗中期开始,一直到治疗后期,参与者通过参与治疗可能已经了解到,与疼痛相关的适应不良想法和/或疼痛峰值的发作不一定会对他们随后的经历产生不利影响。
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引用次数: 0
Retrospective identification of the diagnosis of chronic primary musculoskeletal pain: a pragmatic suggestion by The Pain Net. 慢性原发性肌肉骨骼疼痛诊断的回顾性鉴定:疼痛网的务实建议。
IF 5.9 1区 医学 Q1 ANESTHESIOLOGY Pub Date : 2025-02-01 Epub Date: 2024-09-03 DOI: 10.1097/j.pain.0000000000003380
Helen Koechlin, Cosima Locher, Antonia Barke, Beatrice Korwisi
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引用次数: 0
The physical activity paradox; exploring the relationship with pain outcomes. The Tromsø Study 2015-2016. 体育锻炼悖论;探索与疼痛结果的关系。2015-2016年特罗姆瑟研究。
IF 5.9 1区 医学 Q1 ANESTHESIOLOGY Pub Date : 2025-02-01 Epub Date: 2024-08-26 DOI: 10.1097/j.pain.0000000000003344
Mats Kirkeby Fjeld, Anders Pedersen Årnes, Bo Engdahl, Bente Morseth, Laila Arnesdatter Hopstock, Alexander Horsch, Audun Stubhaug, Bjørn Heine Strand, Anette Hylen Ranhoff, Dagfinn Matre, Christopher Sivert Nielsen, Ólöf Anna Steingrímsdóttir

Abstract: Paradoxical associations have been observed for leisure-time physical activity (LTPA) and occupational physical activity (OPA) and several health-related outcomes. Typically, higher LTPA is associated with health benefits and high OPA with health hazards. Using data from the Tromsø Study (2015-2016), we assessed how questionnaire-based LTPA and OPA (n = 21,083) and accelerometer-measured physical activity (PA) (n = 6778) relate to pain outcomes. Leisure-time physical activity and OPA were categorized as inactive PA, low PA, and moderate-to-vigorous PA and then aggregated into 9 levels, eg, inactive LTPA/inactive OPA. Accelerometer-measured PA included counts/minute, steps/day, and WHO PA recommendations from 2010 to 2020. Three binary pain outcomes (any pain, any chronic pain, and moderate-to-severe chronic pain) were constructed based on pain location, intensity, duration, and impact on daily activities. By using Poisson regression to estimate absolute and relative associations, we found that high LTPA was associated with lower pain prevalence and vice versa for OPA. Compared to inactive LTPA, prevalence ratio (PR) with 95% confidence intervals was lowest for moderate-to-vigorous LTPA, 0.93 (0.89-0.96) for any pain, 0.88 (0.84-0.93) for any chronic pain, and 0.66 (0.59-0.75) for moderate-to-severe chronic pain. Compared to sedentary OPA, the ratio was highest for moderate-to-vigorous OPA, 1.04 (1.01-1.07) for any pain, 1.06 (1.02-1.10) for any chronic pain, and 1.33 (1.21-1.46) for moderate-to-severe chronic pain. Aggregated LTPA and OPA showed lower outcomes for moderate-to-vigorous LTPA combined with lower levels of OPA. Higher levels of accelerometer-measured PA were associated with less pain. To summarize, we found inverse associations for LTPA and OPA. Benefits from LTPA seem to depend on low levels of OPA.

摘要:人们观察到闲暇时间体育活动(LTPA)和职业体育活动(OPA)与若干健康相关结果之间存在着矛盾的联系。通常情况下,较高的闲暇时间体力活动与健康益处相关,而较高的职业体力活动与健康危害相关。利用特罗姆瑟研究(2015-2016 年)的数据,我们评估了基于问卷的 LTPA 和 OPA(n = 21083)以及加速度计测量的体力活动(PA)(n = 6778)与疼痛结果的关系。闲暇时间体力活动和OPA分为非活跃PA、低PA和中度至剧烈PA,然后汇总为9个等级,如非活跃LTPA/非活跃OPA。加速度计测量的PA包括计数/分钟、步数/天以及世界卫生组织2010年至2020年的PA建议。根据疼痛的部位、强度、持续时间和对日常活动的影响,构建了三种二元疼痛结果(任何疼痛、任何慢性疼痛和中度至重度慢性疼痛)。通过使用泊松回归估算绝对和相对关联,我们发现高LTPA与较低的疼痛患病率相关,反之亦然。与不活跃的LTPA相比,中度至剧烈LTPA的患病率比值(PR)(95%置信区间)最低,任何疼痛的患病率比值为0.93(0.89-0.96),任何慢性疼痛的患病率比值为0.88(0.84-0.93),中度至严重慢性疼痛的患病率比值为0.66(0.59-0.75)。与久坐不动的 OPA 相比,中度至剧烈 OPA 的比率最高,任何疼痛为 1.04(1.01-1.07),任何慢性疼痛为 1.06(1.02-1.10),中度至重度慢性疼痛为 1.33(1.21-1.46)。LTPA和OPA的综合结果显示,中度至剧烈LTPA加上较低水平的OPA会导致较低的结果。加速度计测量的较高水平的活动量与较轻的疼痛相关。总之,我们发现,LTPA 和 OPA 呈反向关系。LTPA的益处似乎取决于低水平的OPA。
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引用次数: 0
Further evidence on gabapentinoid efficacy is required but work in this field will be challenging. 需要进一步的证据证明加巴喷丁类药物的有效性,但这一领域的工作将具有挑战性。
IF 5.9 1区 医学 Q1 ANESTHESIOLOGY Pub Date : 2025-02-01 Epub Date: 2024-10-10 DOI: 10.1097/j.pain.0000000000003454
Sara Muller, James Bailey, Ram Bajpai, Toby Helliwell, Sarah A Harrisson, Rebecca Whittle, Christian D Mallen, Julie Ashworth
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引用次数: 0
Species-specific differences and the role of Na v 1.9 in pain pathophysiology. 物种特异性差异和 Nav1.9 在疼痛病理生理学中的作用。
IF 5.9 1区 医学 Q1 ANESTHESIOLOGY Pub Date : 2025-02-01 Epub Date: 2024-09-19 DOI: 10.1097/j.pain.0000000000003395
Sulayman D Dib-Hajj, Stephen G Waxman
{"title":"Species-specific differences and the role of Na v 1.9 in pain pathophysiology.","authors":"Sulayman D Dib-Hajj, Stephen G Waxman","doi":"10.1097/j.pain.0000000000003395","DOIUrl":"10.1097/j.pain.0000000000003395","url":null,"abstract":"","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"231-233"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Functional connectivity associations with menstrual pain characteristics in adolescents: an investigation of the triple network model. 功能连接与青少年痛经特征的关联:对三重网络模型的研究。
IF 5.9 1区 医学 Q1 ANESTHESIOLOGY Pub Date : 2025-02-01 Epub Date: 2024-07-18 DOI: 10.1097/j.pain.0000000000003334
Laura A Payne, Laura C Seidman, Vitaly Napadow, Lisa D Nickerson, Poornima Kumar

Abstract: Menstrual pain is associated with deficits in central pain processing, yet neuroimaging studies to date have all been limited by focusing on group comparisons of adult women with vs without menstrual pain. This study aimed to investigate the role of the triple network model (TNM) of brain networks in adolescent girls with varied menstrual pain severity ratings. One hundred participants (ages 13-19 years) completed a 6-min resting state functional magnetic resonance imaging (fMRI) scan and rated menstrual pain severity, menstrual pain interference, and cumulative menstrual pain exposure. Imaging analyses included age and gynecological age (years since menarche) as covariates. Menstrual pain severity was positively associated with functional connectivity between the cingulo-opercular salience network (cSN) and the sensory processing regions, limbic regions, and insula, and was also positively associated with connectivity between the left central executive network (CEN) and posterior regions. Menstrual pain interference was positively associated with connectivity between the cSN and widespread brain areas. In addition, menstrual pain interference was positively associated with connectivity within the left CEN, whereas connectivity both within the right CEN and between the right CEN and cortical areas outside the network (including the insula) were negatively associated with menstrual pain interference. Cumulative menstrual pain exposure shared a strong negative association with connectivity between the default mode network and other widespread regions associated with large-scale brain networks. These findings support a key role for the involvement of TNM brain networks in menstrual pain characteristics and suggest that alterations in pain processing exist in adolescents with varying levels of menstrual pain.

摘要:痛经与中枢疼痛处理缺陷有关,但迄今为止的神经影像学研究都局限于对有痛经与无痛经的成年女性进行分组比较。本研究旨在调查大脑网络三重网络模型(TNM)在月经疼痛严重程度不同的少女中的作用。100名参与者(13-19岁)完成了6分钟静息状态功能磁共振成像(fMRI)扫描,并对经痛严重程度、经痛干扰和累积经痛暴露进行了评级。成像分析将年龄和妇科年龄(月经初潮后的年数)作为协变量。经痛严重程度与脑回-小脑突出网络(cSN)、感觉处理区、边缘区和岛叶之间的功能连接呈正相关,与左侧中央执行网络(CEN)和后部区域之间的连接也呈正相关。经痛干扰与 cSN 和广泛脑区之间的连通性呈正相关。此外,经痛干扰与左侧 CEN 内部的连接性呈正相关,而右侧 CEN 内部以及右侧 CEN 与网络外皮层区域(包括岛叶)之间的连接性与经痛干扰呈负相关。累积的经痛暴露与默认模式网络和其他与大规模大脑网络相关的广泛区域之间的连通性呈强烈的负相关。这些研究结果支持TNM脑网络在经痛特征中的关键作用,并表明不同程度经痛的青少年在疼痛处理过程中存在改变。
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引用次数: 0
Visualizing the modulation of neurokinin 1 receptor-positive neurons in the superficial dorsal horn by spinal cord stimulation in vivo. 在体内观察脊髓刺激对浅背角神经激肽 1 受体阳性神经元的调节作用
IF 5.9 1区 医学 Q1 ANESTHESIOLOGY Pub Date : 2025-02-01 Epub Date: 2024-08-13 DOI: 10.1097/j.pain.0000000000003361
Qian Xu, Qin Zheng, Xiang Cui, Andrew Cleland, Juan Hincapie, Srinivasa N Raja, Xinzhong Dong, Yun Guan

Abstract: Spinal cord stimulation (SCS) is an effective modality for pain treatment, yet its underlying mechanisms remain elusive. Neurokinin 1 receptor-positive (NK1R + ) neurons in spinal lamina I play a pivotal role in pain transmission. To enhance our mechanistic understanding of SCS-induced analgesia, we investigated how different SCS paradigms modulate the activation of NK1R + neurons, by developing NK1R-Cre;GCaMP6s transgenic mice and using in vivo calcium imaging of superficial NK1R + neurons under anesthesia (1.5% isoflurane). Neurokinin 1 receptor-positive neurons in the lumbar spinal cord (L4-5) showed a greater activation by electrical test stimulation (TS, 3.0 mA, 1 Hz) at the hindpaw at 2 weeks after tibia-sparing nerve injury (SNI-t) than in naïve mice. Spinal cord stimulation was then delivered through a bipolar plate electrode placed epidurally at L1-2 level. The short-term 50-Hz high-intensity SCS (80% motor threshold [MoT], 10 minutes) induced robust and prolonged inhibition of NK1R + neuronal responses to TS in both naïve and SNI-t mice. The 30-minute 50-Hz and 900-Hz SCS applied at moderate intensity (50% MoT) also significantly inhibited neuronal responses in SNI-t mice. However, at low intensity (20% MoT), the 30-minute 900-Hz SCS only induced persistent neuronal inhibition in naïve mice, but not in SNI-t mice. In conclusion, both 10-minute high-intensity SCS and 30-minute SCS at moderate intensity inhibit the activation of superficial NK1R + neurons, potentially attenuating spinal nociceptive transmission. Furthermore, in vivo calcium imaging of NK1R + neurons provides a new approach for exploring the spinal neuronal mechanisms of pain inhibition by neuromodulation pain therapies.

摘要:脊髓刺激(SCS)是一种有效的疼痛治疗方式,但其潜在机制仍难以捉摸。脊髓I层神经激肽1受体阳性(NK1R+)神经元在疼痛传导中起着关键作用。为了加深我们对 SCS 诱导镇痛的机理的理解,我们通过培育 NK1R-Cre;GCaMP6s 转基因小鼠,并在麻醉(1.5% 异氟醚)状态下对浅表 NK1R+ 神经元进行体内钙成像,研究了不同 SCS 范式如何调节 NK1R+ 神经元的激活。在胫骨神经损伤(SNI-t)2周后,腰椎脊髓(L4-5)中神经激肽1受体阳性神经元在后爪电刺激(TS,3.0 mA,1 Hz)下显示出比正常小鼠更强的激活能力。然后通过放置在L1-2水平硬膜外的双极板电极进行脊髓刺激。50赫兹的短期高强度SCS(80%运动阈值[MoT],10分钟)可诱导NK1R+神经元对TS的反应,并对幼稚小鼠和SNI-t小鼠的TS反应产生强有力的长时间抑制。中等强度(50% MoT)的 30 分钟 50 赫兹和 900 赫兹 SCS 也能显著抑制 SNI-t 小鼠的神经元反应。然而,在低强度(20% MoT)下,30 分钟的 900 Hz SCS 只诱导幼稚小鼠产生持续的神经元抑制,而 SNI-t 小鼠则没有。总之,10 分钟高强度 SCS 和 30 分钟中等强度 SCS 都能抑制浅表 NK1R+ 神经元的激活,从而有可能减轻脊髓痛觉传导。此外,NK1R+神经元的体内钙成像为探索神经调节疼痛疗法抑制疼痛的脊髓神经元机制提供了一种新方法。
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