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Interstitial cystitis—an imbalance of risk and protective factors? 间质性膀胱炎--风险和保护因素失衡?
Pub Date : 2024-05-09 DOI: 10.3389/fpain.2024.1405488
J. Westropp, Judi L. Stella, C. Buffington
Interstitial cystitis (IC) presents as a chronic pain condition with variable combinations of symptoms depending on the species and individual patient. It is diagnosed by the presence of lower urinary tract signs and symptoms in combination with a variety of comorbid health problems, a history of life adversities, and the absence of other conditions that could cause the lower urinary tract signs. IC occurs naturally in humans and cats as a dimensional condition, with patients presenting with mild, moderate, and severe symptoms. Most patients appear to recover without specific treatment. A number of rodent models of IC have been used to study its causes and treatments. Unfortunately, current therapies generally fail to ameliorate IC symptoms long-term. The recent classification of IC as a chronic primary pain disorder calls for a rethinking of current clinical and research approaches to it. Beginning when a patient encounters a clinician, precipitating, perpetuating, and palliating risk factors can be addressed until a cause or reliably effective therapy is identified, and identifying predisposing and preventive factors can inform epidemiological studies and health promotion interventions. Predisposing, precipitating, and perpetuating risk factors, including environmental, psychological, and biological, increase the activity of the central threat response system (CTRS), which plays a clinically important role in IC symptoms. Studies in cats and rodent models have revealed that environmental enrichment (EE), in the absence of bladder-directed therapies, leads to amelioration of IC symptoms, implying a central role for the CTRS in symptom precipitation and perpetuation. Conceptually moving the source of IC pain to the brain as a motivational state rather than one resulting from peripheral nociceptive input offers both clinicians and researchers novel opportunities to improve care for patients with IC and for researchers to use more ecologically valid rodent models. It may even be that IC results from an excess of risk to protective factors, making this imbalance a targetable cause rather than a consequence of IC.
间质性膀胱炎(IC)是一种慢性疼痛疾病,因病种和患者个体不同而有不同的症状组合。它的诊断依据是下尿路症状和体征的出现,同时伴有各种合并健康问题、生活逆境史,以及不存在可能导致下尿路症状的其他疾病。IC 在人类和猫科动物中自然发生,患者表现为轻度、中度和重度症状。大多数患者似乎无需特殊治疗即可痊愈。许多啮齿类动物模型都被用来研究 IC 的病因和治疗方法。遗憾的是,目前的疗法通常无法长期改善 IC 症状。最近,IC 被归类为慢性原发性疼痛疾病,这就要求我们重新思考当前的临床和研究方法。在找到病因或可靠有效的治疗方法之前,可以从患者与临床医生接触开始,对诱发、延续和缓解风险因素进行处理,而确定易感因素和预防因素可以为流行病学研究和健康促进干预措施提供依据。包括环境、心理和生物在内的易感、诱发和持续风险因素会增加中枢威胁反应系统(CTRS)的活性,而该系统在 IC 症状中发挥着重要的临床作用。对猫和啮齿动物模型的研究表明,在没有膀胱导向疗法的情况下,环境强化(EE)可改善 IC 症状,这意味着中枢威胁反应系统(CTRS)在症状沉淀和持续方面发挥着核心作用。从概念上讲,将 IC 疼痛的源头转移到大脑是一种动机状态,而不是外周痛觉输入所导致的状态,这为临床医生和研究人员提供了新的机会来改善对 IC 患者的护理,也为研究人员提供了使用更多生态学上有效的啮齿类动物模型的机会。IC 甚至可能是风险因素多于保护因素的结果,因此这种不平衡是 IC 的一个目标原因,而不是结果。
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引用次数: 0
Characterization of pain-related behaviors in a rat model of acute-to-chronic low back pain: single vs. multi-level disc injury 急性至慢性腰痛大鼠模型中与疼痛有关的行为特征:单层椎间盘损伤与多层椎间盘损伤
Pub Date : 2024-05-06 DOI: 10.3389/fpain.2024.1394017
M. Barbe, Frank Liu Chen, Regina H. Loomis, M. Harris, Brandon M. Kim, Kevin Xie, Brendan A. Hilliard, Elizabeth R. McGonagle, Taylor D. Bailey, Ryan P. Gares, Megan Van Der Bas, Betsy A. Kalicharan, Lewis Holt-Bright, Laura S. Stone, Paul W Hodges, D. Klyne
Low back pain is the most common type of chronic pain. We examined pain-related behaviors across 18 weeks in rats that received injury to one or two lumbar intervertebral discs (IVD) to determine if multi-level disc injuries enhance/prolong pain.Twenty-three Sprague-Dawley adult female rats were used: 8 received disc puncture (DP) of one lumbar IVD (L5/6, DP-1); 8 received DP of two lumbar IVDs (L4/5 & L5/6, DP-2); 8 underwent sham surgery.DP-2 rats showed local (low back) sensitivity to pressure at 6- and 12-weeks post-injury, and remote sensitivity to pressure (upper thighs) at 12- and 18-weeks and touch (hind paws) at 6, 12 and 18-weeks. DP-1 rats showed local and remote pressure sensitivity at 12-weeks only (and no tactile sensitivity), relative to Sham DP rats. Both DP groups showed reduced distance traveled during gait testing over multiple weeks, compared to pre-injury; only DP-2 rats showed reduced distance relative to Sham DP rats at 12-weeks. DP-2 rats displayed reduced positive interactions with a novel adult female rat at 3-weeks and hesitation and freezing during gait assays from 6-weeks onwards. At study end (18-weeks), radiological and histological analyses revealed reduced disc height and degeneration of punctured IVDs. Serum BDNF and TNFα levels were higher at 18-weeks in DP-2 rats, relative to Sham DP rats, and levels correlated positively with remote sensitivity in hind paws (tactile) and thighs (pressure).Thus, multi-level disc injuries resulted in earlier, prolonged and greater discomfort locally and remotely, than single-level disc injury. BDNF and TNFα may have contributing roles.
腰痛是最常见的慢性疼痛类型。我们研究了一只或两只腰椎间盘(IVD)受伤的大鼠在18周内与疼痛相关的行为,以确定多层次椎间盘损伤是否会增强/延长疼痛:8只大鼠接受了一个腰椎间盘穿刺术(DP)(L5/6,DP-1);8只大鼠接受了两个腰椎间盘穿刺术(L4/5和L5/6,DP-2);8只大鼠接受了假手术。DP-2大鼠在伤后6周和12周表现出对压力的局部(腰部)敏感性,在伤后12周和18周表现出对压力(大腿上部)的远端敏感性,在伤后6周、12周和18周表现出对触觉(后爪)的远端敏感性。与 Sham DP 大鼠相比,DP-1 大鼠仅在 12 周时表现出局部和远程压力敏感性(没有触觉敏感性)。与受伤前相比,DP 两组大鼠在多周步态测试中的行走距离都有所减少;只有 DP-2 组大鼠在 12 周时的行走距离相对于 Sham DP 组大鼠有所减少。DP-2 组大鼠在 3 周时与一只新的成年雌性大鼠的积极互动减少,从 6 周起在步态测试中表现出犹豫和凝滞。研究结束时(18 周),放射学和组织学分析显示,椎间盘高度降低,穿孔的 IVD 退化。与Sham DP大鼠相比,DP-2大鼠在18周时的血清BDNF和TNFα水平较高,其水平与后爪(触觉)和大腿(压力)的远端敏感性呈正相关。BDNF和TNFα可能起到了促进作用。
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引用次数: 0
Editorial: Yoga for pain relief 社论:缓解疼痛的瑜伽
Pub Date : 2024-05-06 DOI: 10.3389/fpain.2024.1422483
Pradeep M. K. Nair, J. Keswani, H. S. Vadiraja
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引用次数: 0
Should cancer pain still be considered a separate category alongside acute pain and chronic non-cancer pain? Reflections on ICD-11 癌症疼痛是否仍应被视为与急性疼痛和慢性非癌症疼痛并列的一个单独类别?关于 ICD-11 的思考
Pub Date : 2024-05-02 DOI: 10.3389/fpain.2024.1397413
Emmanuel Bäckryd
Introduction Traditionally, cancer pain has often been viewed as an independent third major category in pain medicine alongside acute pain and chronic non-cancer pain. However, the new chronic pain category MG30 in the eleventh version of International Classification of Diseases (ICD-11) includes cancer-related pain as one of its seven subgroups. In light of this, the aim of the paper is to investigate whether the traditional trichotomy should be replaced by a dichotomy between acute pain and chronic pain, cancer-related pain being part of both groups depending on the duration of pain. Methods The rationale for viewing cancer pain as a separate category is reviewed. Results Cancer being a deadly disease, cancer pain has a life-and-death and existential dimension that is different from non-cancer pain. It seems sensible to believe that this is an additional dimension to the suffering caused by cancer pain, and that clinicians should therefore take this existential dimension into consideration when assessing pain. Conclusion Without challenging the place of chronic cancer-related pain under the MG30 heading, it is concluded that while using ICD-11 in the future, pain clinicians should continue being mindful of the fact that the reality of death shapes the experience of cancer pain. The traditional trichotomy is therefore still valid and mirrors the fact that human beings are vulnerable (acute pain), temporal (chronic pain) and mortal (cancer pain).
导言:传统上,癌痛通常被视为疼痛医学中独立的第三大类,与急性疼痛和慢性非癌性疼痛并列。然而,在第十一版《国际疾病分类》(ICD-11)中,新的慢性疼痛类别 MG30 将癌症相关疼痛列为其七个亚组之一。有鉴于此,本文旨在探讨是否应将传统的三分法改为急性疼痛和慢性疼痛二分法,根据疼痛持续时间的长短,将癌症相关疼痛分为急性疼痛和慢性疼痛两组。方法 回顾了将癌症疼痛视为一个单独类别的理由。结果 癌症是一种致命的疾病,因此癌症疼痛具有不同于非癌症疼痛的生死和生存维度。我们似乎有理由相信,这是癌痛所造成的痛苦的一个额外维度,因此临床医生在评估疼痛时应将这一存在维度考虑在内。结论 在不质疑与癌症相关的慢性疼痛在 MG30 标题下的地位的前提下,得出的结论是,在未来使用 ICD-11 时,疼痛临床医生应继续注意死亡的现实会影响癌症疼痛的体验这一事实。因此,传统的三分法仍然有效,它反映了人类是脆弱的(急性疼痛)、暂时的(慢性疼痛)和致命的(癌症疼痛)这一事实。
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引用次数: 0
Successes and lessons learned from a mobile health behavior intervention to reduce pain and improve health in older adults with obesity and chronic pain: a qualitative study 为减少肥胖和慢性疼痛老年人的疼痛并改善其健康状况而采取的移动健康行为干预措施的成功经验和教训:一项定性研究
Pub Date : 2024-04-25 DOI: 10.3389/fpain.2024.1340400
A. Brooks, Abha Athawale, Virginia Rush, Abigail Yearout, Sherri Ford, W. Rejeski, Ashley Strahley, Jason Fanning
Chronic pain is a prevalent issue among older adults in the United States that impairs quality of life. Physical activity has emerged as a cost-effective and non-pharmacological treatment for chronic pain, offering benefits such as improved physical functioning, weight loss, and enhanced mood. However, promoting physical activity in older individuals with chronic pain is challenging, given the cyclical relationship between pain and sedentary behavior. The Mobile Intervention to Reduce Pain and Improve Health (MORPH) trial was designed as an innovative, mobile health (mHealth) supported intervention to address this issue by targeting daylong movement, weight loss, and mindfulness to manage pain in older adults with chronic multisite pain. The objective of this paper is to provide the result of a qualitative analysis conducted on post-intervention interviews with MORPH participants.At the conclusion of the MORPH study, 14 participants were interviewed regarding their experience with the program. All interviews were conducted by phone before being transcribed and verified. A codebook of significant takeaways was created based on these accounts. Summaries were further synthesized into themes using the principles of thematic analysis.Three key themes of the MORPH intervention emerged from the qualitative interviews: MORPH technology (smart scales, Fitbit, MORPH Companion App) facilitated program adherence and accountability; MORPH intervention components (food tracking and mindfulness activities) facilitated program adherence and awareness, respectively; and, group meetings provided motivational support and accountability. Mobile health technologies, including a dedicated MORPH app, facilitated self-monitoring strategies, helped to break the cycle of old habits, and provided participants with immediate feedback on successes; however, technical issues required timely support to maintain engagement. Food tracking contributed to adherence and accountability for weight loss. Mindfulness activities increased participants’ awareness of anxiety provoking thoughts and pain triggers. Finally, social support via group meetings and connection, played a crucial role in behavior change, but participants noted consistency in the delivery medium was essential to fostering genuine connections.Overall, the study results highlight the key considerations related to program technology, intervention components, and the value of social support that can help to guide the development of future interventions similar to MORPH.
慢性疼痛是美国老年人中普遍存在的问题,有损生活质量。体育锻炼已成为治疗慢性疼痛的一种具有成本效益的非药物疗法,具有改善身体机能、减轻体重和提高情绪等益处。然而,鉴于疼痛与久坐行为之间的周期性关系,在患有慢性疼痛的老年人中推广体育锻炼具有挑战性。减少疼痛和改善健康的移动干预(MORPH)试验旨在通过针对患有慢性多部位疼痛的老年人的日间运动、减肥和正念来控制疼痛,从而作为一种创新的、移动健康(mHealth)支持的干预措施来解决这一问题。本文旨在提供对 MORPH 参与者进行干预后访谈的定性分析结果。在 MORPH 研究结束时,对 14 名参与者进行了访谈,了解他们对该计划的体验。所有访谈均通过电话进行,然后再进行转录和核实。根据这些叙述,我们创建了一个重要收获的编码本。定性访谈中出现了 MORPH 干预的三个关键主题:MORPH 技术(智能秤、Fitbit、MORPH 同伴应用程序)促进了计划的坚持和责任感;MORPH 干预组件(食物跟踪和正念活动)分别促进了计划的坚持和意识的提高;小组会议提供了动力支持和责任感。移动健康技术,包括专门的 MORPH 应用程序,促进了自我监控策略,有助于打破旧习惯的循环,并为参与者提供了即时的成功反馈;然而,技术问题需要及时的支持,以保持参与度。食物追踪有助于坚持减肥并对减肥负责。正念活动提高了参与者对引发焦虑的想法和疼痛诱因的认识。最后,通过小组会议和联系提供的社会支持在行为改变中发挥了至关重要的作用,但参与者指出,传递媒介的一致性对于培养真正的联系至关重要。总之,研究结果强调了与计划技术、干预内容和社会支持价值相关的关键考虑因素,有助于指导未来开发类似于 MORPH 的干预措施。
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引用次数: 0
Case Report: Phantom limb pain relief after cognitive multisensory rehabilitation 病例报告:认知多感官康复后缓解幻肢痛
Pub Date : 2024-04-25 DOI: 10.3389/fpain.2024.1374141
Marina Zernitz, Carla Rizzello, Marco Rigoni, Ann Van de Winckel
Relieving phantom limb pain (PLP) after amputation in patients resistant to conventional therapy remains a challenge. While the causes for PLP are unclear, one model suggests that maladaptive plasticity related to cortical remapping following amputation leads to altered mental body representations (MBR) and contributes to PLP. Cognitive Multisensory Rehabilitation (CMR) has led to reduced pain in other neurologic conditions by restoring MBR. This is the first study using CMR to relieve PLP.A 26-year-old woman experienced excruciating PLP after amputation of the third proximal part of the leg, performed after several unsuccessful treatments (i.e., epidural stimulator, surgeries, analgesics) for debilitating neuropathic pain in the left foot for six years with foot deformities resulting from herniated discs. The PLP was resistant to pain medication and mirror therapy. PLP rendered donning a prosthesis impossible. The patient received 35 CMR sessions (2×/day during weekdays, October–December 2012). CMR provides multisensory discrimination exercises on the healthy side and multisensory motor imagery exercises of present and past actions in both limbs to restore MBR and reduce PLP.After CMR, PLP reduced from 6.5–9.5/10 to 0/10 for neuropathic pain with only 4–5.5/10 for muscular pain after exercising on the Numeric Pain Rating Scale. McGill Pain Questionnaire scores reduced from 39/78 to 5/78, and Identity (ID)-Pain scores reduced from 5/5 to 0/5. Her pain medication was reduced by at least 50% after discharge. At 10-month follow-up (9/2013), she no longer took Methadone or Fentanyl. After discharge, receiving CMR as outpatient, she learned to walk with a prosthesis, and gradually did not need crutches anymore to walk independently indoors and outdoors (9/2013). At present (3/2024), she no longer takes pain medication and walks independently with the prosthesis without assistive devices. PLP is under control. She addresses flare-ups with CMR exercises on her own, using multisensory motor imagery, bringing the pain down within 10–15 min.The case study seems to support the hypothesis that CMR restores MBR which may lead to long-term (12-year) PLP reduction. MBR restoration may be linked to restoring accurate multisensory motor imagery of the remaining and amputated limb regarding present and past actions.
缓解对传统疗法有抵抗力的截肢患者的幻肢痛(PLP)仍然是一项挑战。虽然幻肢痛的原因尚不清楚,但有一种模式认为,截肢后与大脑皮层重映射有关的不适应可塑性会导致心理肢体表征(MBR)的改变,从而导致幻肢痛。认知多感官康复(CMR)可通过恢复躯体表征来减轻其他神经系统疾病的疼痛。一名 26 岁的女性因左脚神经性疼痛衰弱六年并伴有椎间盘突出导致的足部畸形,在多次治疗(如硬膜外刺激器、手术、止痛药)未果的情况下截肢了第三条腿的近端部分,之后经历了剧烈的 PLP。PLP 对止痛药和镜像疗法产生了抗药性。PLP 导致无法穿戴假肢。患者接受了 35 次 CMR 治疗(2012 年 10 月至 12 月,工作日每天 2 次)。CMR 提供健侧的多感官辨别练习和双侧肢体现在和过去动作的多感官运动想象练习,以恢复 MBR 并减少 PLP。CMR 治疗后,神经性疼痛的 PLP 从 6.5-9.5/10 降至 0/10,肌肉疼痛的 PLP 仅为 4-5.5/10。麦吉尔疼痛问卷评分从 39/78 降至 5/78,身份(ID)-疼痛评分从 5/5 降至 0/5。出院后,她的止痛药至少减少了 50%。在 10 个月的随访中(2013 年 9 月),她不再服用美沙酮或芬太尼。出院后,她在门诊接受了 CMR 治疗,学会了使用假肢行走,逐渐不再需要拐杖就能在室内外独立行走(2013 年 9 月)。目前(2024 年 3 月),她已不再服用止痛药,并在没有辅助设备的情况下使用假肢独立行走。PLP 已得到控制。该病例研究似乎支持这样的假设:CMR 可恢复 MBR,从而长期(12 年)减少 PLP。MBR 的恢复可能与恢复残肢和截肢对当前和过去动作的准确多感官运动想象有关。
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引用次数: 0
Pressure pain mapping of equine distal joints: feasibility and reliability 马远端关节压痛绘图:可行性和可靠性
Pub Date : 2024-04-25 DOI: 10.3389/fpain.2024.1342954
Jana Gisler, Ludovica Chiavaccini, Severin Blum, Stéphane Montavon, Claudia Spadavecchia
Osteoarthritis is a prevalent degenerative joint disease initiating chronic pain and lameness in horses. While several objective gait analysis systems have been developed and validated to quantify lameness severity in horses, methods to evaluate whether peripheral sensitization contributes to the pain experienced are missing.To evaluate whether periarticular pressure pain mapping could be proposed as an auxiliary assessment tool in horses. Specific aims were to evaluate the feasibility and intra- and inter-rater reliability of pressure pain thresholds (PPT) determination at sites overlying the distal thoracic limb joints of clinically healthy horses.Prospective, randomized validation study.For feasibility assessment, PPT were measured with a hand-held digital algometer at six periarticular landmarks (2 sites per joint, 3 joints) bilaterally on the distal thoracic limb of 40 healthy horses (20 warmblood and 20 Freiberger). The joints tested were the metacarpophalangeal, on the latero-palmar and dorsal aspects (L-MCP and D-MCP), the proximal interphalangeal, on the dorsal and palmar aspect (D-PIP and P-PIP) and the distal interphalangeal, on the dorsal and lateral aspect (D-DIP and L-DIP). A feasibility score, ranging from 0 to 5, was attributed to each testing session. For intra- and inter-rater reliability assessment, L-MCP and D-MCP were selected to be tested again at 2 weeks intervals in 20 out of the 40 horses. Data were analyzed using a mixed-effect linear model to test differences in threshold per site and limb. Intra- and inter-rater correlation was calculated. Bland-Altman plots were performed to evaluate the variability of the measures.The procedure was considered feasible (score <2) in 95% of horses (95% CI 88%–100%). Overall, median [interquartile range (IQR)] PPT was 9.4 (7.5–11.3) N. No significant side differences were found. P-PIP and D-DIP recorded significantly lower PPT (p < 0.001 and p = 0.002, respectively) than L-MCP. Median (IQR) were 9.9 (7.3–12.4) N, 8.4 (6.1–10.5) N and 9.0 (7.4–10.6) N for L-MCP, P-PIP and D-DIP, respectively. The intra-rater agreement was 0.68 (95% CI 0.35–0.86) for L-MCP, and 0.50 (95% CI 0.08–0.76) for D-MCP. Inter-rater agreement was 0.85 (95% CI 0.66–0.94) for L-MCP and 0.81 (0.57, 0.92) for D-MCP.Evaluation of feasibility was performed only for distal thoracic limbs joints; no data are provided for hind limbs or proximal joints. Only warmblood and Freiberger horses were included. Intra- and inter-rater reliability assessments were performed exclusively on data collected at the MCP joint.Pressure pain mapping of distal thoracic limb joints was feasible in horses. Local sensitivity differed among sites and no side differences were noticed. Data collected from the MCP joint suggest highly variable, subject dependent intra-rater reliability, ranging from poor to good, and good to excellent inter-rater reliability. Further studies evaluating pathologic vs. healthy joints are needed before recommendations
骨关节炎是一种常见的退行性关节疾病,会导致马匹慢性疼痛和跛行。虽然已经开发并验证了几种客观步态分析系统来量化马匹跛行的严重程度,但还缺少评估外周敏感性是否会导致疼痛的方法。具体目的是评估在临床健康马匹的胸肢远端关节上方部位测定压痛阈值(PPT)的可行性以及评分者内部和评分者之间的可靠性。为了进行可行性评估,使用手持式数字测距仪在 40 匹健康马匹(20 匹温血马和 20 匹弗莱贝格马)的胸肢远端双侧 6 个关节周围地标(每个关节 2 个部位,3 个关节)处测量压痛阈值。测试的关节包括掌指关节的掌侧和背侧(L-MCP 和 D-MCP)、近端指间关节的背侧和掌侧(D-PIP 和 P-PIP)以及远端指间关节的背侧和外侧(D-DIP 和 L-DIP)。每个测试环节的可行性评分从 0 到 5 分不等。为了对评分者内部和评分者之间的可靠性进行评估,在 40 匹马中选择了 20 匹马的 L-MCP 和 D-MCP 间隔 2 周再次进行测试。数据采用混合效应线性模型进行分析,以检验每个部位和肢体阈值的差异。计算了评分者内部和评分者之间的相关性。95%的马匹(95% CI 88%-100%)认为该方法可行(得分<2)。总体而言,PPT 的中位数[四分位数间距 (IQR)] 为 9.4 (7.5-11.3) N。P-PIP 和 D-DIP 的 PPT 值明显低于 L-MCP(分别为 p < 0.001 和 p = 0.002)。L-MCP、P-PIP和D-DIP的中位数(IQR)分别为9.9(7.3-12.4)N、8.4(6.1-10.5)N和9.0(7.4-10.6)N。L-MCP 的评分者内部一致性为 0.68(95% CI 0.35-0.86),D-MCP 为 0.50(95% CI 0.08-0.76)。仅对胸肢远端关节进行了可行性评估,未提供后肢或近端关节的数据。只有温血马和弗莱贝格尔马被纳入评估范围。马匹胸肢远端关节压痛绘图是可行的。不同部位的局部灵敏度不同,但没有发现两侧的差异。从 MCP 关节处收集的数据表明,评分者内部的可靠性变化很大,从较差到良好不等,评分者之间的可靠性从良好到出色不等。在就临床可用性和诊断有效性提出建议之前,还需要对病理关节和健康关节进行进一步的评估研究。
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引用次数: 0
Forced swim stress exacerbates inflammation-induced hyperalgesia and oxidative stress in the rat trigeminal ganglia 强迫游泳应激会加剧炎症诱发的大鼠三叉神经节高痛感和氧化应激
Pub Date : 2024-04-24 DOI: 10.3389/fpain.2024.1372942
Jin Y. Ro, Youping Zhang, J. Asgar, Huizhong Shou, Man-Kyo Chung, O. Melemedjian, Joyce T. Da Silva, Shou Chen
This study investigates the impact of combining psychophysical stress, induced by forced swim (FSS), with masseter inflammation on reactive oxygen species (ROS) production in trigeminal ganglia (TG), TRPA1 upregulation in TG, and mechanical hyperalgesia. In a rat model, we demonstrate that FSS potentiates and prolongs CFA-induced ROS upregulation within TG. The ROS levels in CFA combined with FSS group surpass those in the CFA-only group on days 4 and 28 post-treatment. FSS also enhances TRPA1 upregulation in TG, with prolonged expression compared to CFA alone. Furthermore, CFA-induced mechanical hyperalgesia is significantly prolonged by FSS, persisting up to day 28. PCR array analyses reveal distinct alterations in oxidative stress genes under CFA and CFA combined with FSS conditions, suggesting an intricate regulation of ROS within TG. Notably, genes like Nox4, Hba1, Gpx3, and Duox1 exhibit significant changes, providing potential targets for managing oxidative stress and inflammatory pain. Western blot and immunohistochemistry confirm DUOX1 protein upregulation and localization in TG neurons, indicating a role in ROS generation under inflammatory and stress conditions. This study underscores the complex interplay between psychophysical stress, inflammation, and oxidative stress in the trigeminal system, offering insights into novel therapeutic targets for pain management.
本研究探讨了强迫游泳(FSS)诱导的心理物理应激与咀嚼肌炎症相结合对三叉神经节(TG)活性氧(ROS)产生、三叉神经节 TRPA1 上调和机械性痛觉减退的影响。在大鼠模型中,我们证明了 FSS 能增强和延长 CFA 诱导的三叉神经节内 ROS 上调。在治疗后第 4 天和第 28 天,CFA 联合 FSS 组的 ROS 水平超过了纯 CFA 组。与单独使用 CFA 相比,FSS 还能增强 TG 中 TRPA1 的上调,并延长其表达时间。此外,FSS 还显著延长了 CFA 诱导的机械痛感,并持续到第 28 天。PCR 阵列分析显示,在 CFA 和 CFA 结合 FSS 的条件下,氧化应激基因发生了不同的变化,这表明 TG 内的 ROS 调节错综复杂。值得注意的是,Nox4、Hba1、Gpx3 和 Duox1 等基因发生了显著变化,为控制氧化应激和炎性疼痛提供了潜在靶点。Western 印迹和免疫组化证实了 DUOX1 蛋白在 TG 神经元中的上调和定位,表明其在炎症和应激条件下产生 ROS 的过程中发挥作用。这项研究强调了三叉神经系统中心理物理压力、炎症和氧化应激之间复杂的相互作用,为疼痛治疗提供了新的治疗靶点。
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引用次数: 0
Program of All-Inclusive Care for the Elderly: an untapped setting for research to advance pain care in older persons 老年人全包护理计划:促进老年人疼痛护理研究的未开发环境
Pub Date : 2024-04-22 DOI: 10.3389/fpain.2024.1347473
C. Riffin, Lauren Mei, Lilla A Brody, Keela Herr, Karl A. Pillemer, M. C. Reid
The Program of All-Inclusive Care for the Elderly (PACE) is a community-based care model in the United States that provides comprehensive health and social services to frail, nursing home-eligible adults aged 55 years and older. PACE organizations aim to support adequate pain control in their participants, yet few evidence-based pain interventions have been adopted or integrated into this setting. This article provides a roadmap for researchers who are interested in collaborating with PACE organizations to embed and evaluate evidence-based pain tools and interventions. We situate our discussion within the Consolidated Framework for Implementation Research (CFIR), a meta-theoretical framework that considers multi-level influences to implementation and evaluation of evidence-based programs. Within each CFIR domain, we identify key factors informed by our own work that merit consideration by research teams and PACE collaborators. Inner setting components pertain to the organizational culture of each PACE organization, the type and quality of electronic health record data, and availability of staff to assist with data abstraction. Outer setting components include external policies and regulations by the National PACE Association and audits conducted by the Centers for Medicare and Medicaid Services, which have implications for research participant recruitment and enrollment. Individual-level characteristics of PACE organization leaders include their receptivity toward new innovations and perceived ability to implement them. Forming and sustaining research-PACE partnerships to deliver evidence-based pain interventions pain will require attention to multi-level factors that may influence future uptake and provides a way to improve the health and well-being of patients served by these programs.
老年人全包护理计划(PACE)是美国一种基于社区的护理模式,为 55 岁及以上符合养老院条件的体弱成年人提供全面的健康和社会服务。PACE 组织旨在支持参与者充分控制疼痛,但很少有循证疼痛干预措施被采用或整合到这一环境中。本文为有兴趣与 PACE 机构合作的研究人员提供了一个路线图,以嵌入和评估循证疼痛工具和干预措施。我们将讨论置于 "实施研究综合框架"(CFIR)中,这是一个元理论框架,考虑了对循证项目实施和评估的多层次影响。在 CFIR 的各个领域中,我们根据自己的工作确定了值得研究团队和 PACE 合作者考虑的关键因素。内部环境因素涉及每个 PACE 机构的组织文化、电子健康记录数据的类型和质量,以及是否有员工协助进行数据抽取。外部环境因素包括国家 PACE 协会的外部政策和法规,以及医疗保险和医疗补助服务中心进行的审计,这些因素对研究参与者的招募和注册都有影响。PACE 组织领导者的个人特征包括他们对新创新的接受程度以及实施新创新的能力。要形成并维持研究与 PACE 的合作关系,以提供循证疼痛干预措施,就需要关注可能影响未来吸收的多层次因素,并为改善这些计划所服务的患者的健康和福祉提供一种方法。
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引用次数: 0
Chronic pain as an emergent property of a complex system and the potential roles of psychedelic therapies 慢性疼痛作为复杂系统的一种突发特性以及迷幻疗法的潜在作用
Pub Date : 2024-04-19 DOI: 10.3389/fpain.2024.1346053
Maya Armstrong, Joel Castellanos, Devon Christie
Despite research advances and urgent calls by national and global health organizations, clinical outcomes for millions of people suffering with chronic pain remain poor. We suggest bringing the lens of complexity science to this problem, conceptualizing chronic pain as an emergent property of a complex biopsychosocial system. We frame pain-related physiology, neuroscience, developmental psychology, learning, and epigenetics as components and mini-systems that interact together and with changing socioenvironmental conditions, as an overarching complex system that gives rise to the emergent phenomenon of chronic pain. We postulate that the behavior of complex systems may help to explain persistence of chronic pain despite current treatments. From this perspective, chronic pain may benefit from therapies that can be both disruptive and adaptive at higher orders within the complex system. We explore psychedelic-assisted therapies and how these may overlap with and complement mindfulness-based approaches to this end. Both mindfulness and psychedelic therapies have been shown to have transdiagnostic value, due in part to disruptive effects on rigid cognitive, emotional, and behavioral patterns as well their ability to promote neuroplasticity. Psychedelic therapies may hold unique promise for the management of chronic pain.
尽管研究取得了进展,国家和全球卫生组织也发出了紧急呼吁,但数百万慢性疼痛患者的临床治疗效果仍然不佳。我们建议用复杂性科学的视角来看待这个问题,将慢性疼痛概念化为复杂的生物-心理-社会系统的一种新兴属性。我们将与疼痛相关的生理学、神经科学、发展心理学、学习和表观遗传学作为一个组成部分和小系统,这些组成部分和小系统共同作用,并与不断变化的社会环境条件相互作用,形成一个总的复杂系统,从而产生了慢性疼痛这一新兴现象。我们推测,复杂系统的行为可能有助于解释慢性疼痛持续存在的原因,尽管目前有各种治疗方法。从这个角度来看,慢性疼痛可能会受益于在复杂系统中具有较高阶破坏性和适应性的疗法。为此,我们探讨了迷幻辅助疗法,以及这些疗法如何与正念疗法重叠和互补。正念疗法和迷幻疗法都已被证明具有跨诊断价值,部分原因是它们对僵化的认知、情绪和行为模式具有破坏作用,并能促进神经可塑性。迷幻疗法可能在治疗慢性疼痛方面具有独特的前景。
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引用次数: 0
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Frontiers in Pain Research
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