Virtual reality for the treatment of neuropathic pain in people with spinal cord injuries: A scoping review

Context: Virtual and augmented imagery are emerging technologies with potential to reduce the severity and impact of neuropathic pain in people with spinal cord injury (SCI).Objective: We aimed to identify and discuss studies using virtual and augmented reality applications for the management of neuropathic pain in people with spinal cord injury.Methods (data sources, data extraction): A systematic literature search was conducted using PRISMA scoping review guidelines. Articles were searched in PubMed, Embase and Web of Science databases using search terms relating to SCI, virtual and augmented reality and neuropathic pain. With no strong evidence for visual imagery in the treatment of pain in SCI patients, we selected exploratory, feasibility and more rigorous methodologies such as randomized controlled trials and case-control studies. We only selected studies evaluating the effects of visual imagery on neuropathic pain at or below the spinal cord injury level.Results: Of 60 articles located, we included nine articles involving 207 participants. All studies were exploratory using head-mounted devices or 3D and 2D screens with virtual walking or limb movement imagery. Outcomes included pain sensitivity, motor function and body ownership. Eight of the nine studies reported significant reductions in neuropathic pain intensity. However, given small sample sizes in all studies, results may be unreliable.Conclusion: Although the number of studies and individual sample sizes are small, these initial findings are promising. Given the limited options available for the effective treatment of neuropathic SCI pain and early evidence of efficacy, they provide valuable incentive for further research.     

Efficacy of cranial electrotherapy stimulation for neuropathic pain following spinal cord injury: a multi-site randomized controlled trial with a secondary 6-month open-label phase

Background

Chronic pain is a significant problem for many individuals following spinal cord injury (SCI). Unfortunately, SCI-related neuropathic pain has proven to be largely refractory to analgesic medications and other available treatments. Cranial electrotherapy stimulation (CES) has been effective in managing some types of pain. It involves the application of a small amount of current through the head via ear clip electrodes.

Objective

Explore the effectiveness of CES for neuropathic pain in persons with SCI and chronic pain.

Study design

Multi-site, double-blind, sham-controlled study.

Participants

Adults with SCI and chronic neuropathic pain at or below the level of injury were randomized to receive active or sham CES.

Intervention

Application of active CES or sham CES 1 hour daily for 21 days. Six-month open-label phase to assess ‘as-needed’ CES use.

Outcome measures

Change in pre- to post-session pain ratings as well as change in pain intensity, pain interference, pain quality, pain beliefs and coping strategies, general physical and mental health status, depressive symptomatology, perceived stress, and anxiety pre- to post-treatment.

Results

The active group reported a significantly greater average decrease in pain during daily treatments than the sham group (Kruskal–Wallis chi-square = 4.70, P < 0.05). During the 21-day trial, there was a significant group × time interaction for only one outcome variable; the active group showed larger pre- to post-treatment decreases in pain interference than the sham group did (F = 8.50, P < 0.01, d = 0.59).

Conclusions

On average, CES appears to have provided a small but statistically significant improvement in pain intensity and pain interference with few troublesome side effects. Individual results varied from no pain relief to a great deal of relief.     

Pain in patients with spinal cord injury: An A to Z approach

Spinal cord injury is a devastating occurence, an event that alters patients' lives and their families. Individuals with spinal cord injury often have chronic pain. The aim is to present a course with management measures that should be taken at the time of appearance of pain, acute, chronic or both, a multimodal management approach according to pathophysiology, taking into account that its treatment remains unsatisfactory. Also consider involving cognitive, emotional, and social issues for a comprehensive approach to patient with spinal cord injury.     

神经病理性疼痛中脊髓小胶质细胞活化的分子机制

背景 研究表明脊髓小胶质细胞活化对神经元功能调控起重要作用,并可影响脊髓背角伤害性信号的传递进而参与调控神经病理性疼痛(neuropathic pain,NP)的中枢敏化过程. 目的 探讨NP状态下脊髓小胶质细胞活化的分子机制. 内容 分别从脊髓小胶质细胞活化的胞外分子机制和胞内分子机制两方面就与此相关的研究进展作一综述. 趋向 小胶质细胞在NP中的作用将继续成为疼痛研究的热点,对小胶质细胞的深入研究可能使NP得到更为有效的治疗.     

Weight gain following spinal cord injury: a pilot study

Study design

Retrospective chart review.

Objective

To define the temporal course of weight gain in persons with new spinal cord injury (SCI), and to identify predictors of weight gain in this population.

Setting

A United States Department of Veterans Affairs (VA) SCI Unit.

Methods

A retrospective chart review in a VA SCI Unit was conducted. Participants (n = 85) included all persons with new SCI completing initial rehabilitation at the center between 1998 and 2006. Outcome measures were mean change in body mass index (BMI) between rehabilitation admission and final follow-up, time of greatest BMI change, and distribution of participants by BMI classification. These measures were also examined relative to SCI level, American Spinal Injury Association Impairment Scale (AIS) grade, primary mode of mobility, and age at rehabilitation admission.

Results

Mean BMI increased by 2.3 kg/m² between rehabilitation admission (mean 45 days post-injury) and final follow-up (mean 5 years post-injury). The distribution of participants shifted from lower BMI classifications at rehabilitation admission to higher BMI classifications at final follow-up. For participants transitioning from normal to overweight or obese, the greatest increase occurred during the first year after acute rehabilitation. Neurological level, impairment category, primary mode of mobility, and age at rehabilitation admission did not significantly predict BMI change. BMI at rehabilitation admission correlated significantly with BMI at final follow-up (P < 0.0005).

Conclusions

These findings confirm a significant increase in BMI after new SCI and suggest that persons with new SCI are at greatest weight gain risk during the first year following acute rehabilitation.     

A scoping review on the effect of cannabis on pain intensity in people with spinal cord injury

ContextThis scoping review examines the current research on the effect of cannabis upon pain intensity in spinal cord injury (SCI) pain. Chronic pain is a significant secondary condition following SCI, and traditional treatments (e.g. opioids, NSAIDs) are often criticized for providing inadequate relief. As a result, there is increasing interest in and use of cannabis and cannabinoid-based medications as an alternative means of pain control.ObjectiveThe purpose of this review was to examine the scientific evidence on the effect of cannabis/cannabinoids upon pain intensity in SCI by mapping the current literature.MethodsTwo hundred and fifty-two studies were identified by searching electronic databases for articles published through February 2020. In addition, reviewers scanned the reference lists of identified articles and examined clinicaltrials.gov for unpublished data in this area. Title, abstract, and full-text reviews were completed by two independent reviewers. Data extraction was performed by a single reviewer and verified by a second reviewer.ResultsSix articles covering five treatment studies were included. Studies yielded mixed findings likely due to large variability in methodology, including lack of standardized dosing paradigms, modes of use, and duration of trial.ConclusionsThe current quality and level of evidence is insufficient to draw reliable conclusions of the efficacy of cannabis upon SCI-related pain itensity. We identify specific limitations of past studies and present guidelines for future research.Trial registration: ClinicalTrials.gov identifier: Nct01606202..     

神经病理性疼痛大鼠脊髓背角一氧化氮合酶各亚型的表达及活性变化

目的 比较神经病理性疼痛大鼠模型脊髓背角中神经型(nNOS),诱导型(iNOS)和内皮型(eNOS)三种一氧化氮合酶(NOS)的表达及活性变化.方法 雌性SD大鼠20只,150～200 g,随机均分为坐骨神经保留性损伤(SNI)组和对照组.SNI组大鼠于左后肢制备SNI模型,对照组大鼠暴露坐骨神经后立即缝合手术切口.术后观测疼痛的变化,于术后第14天断头处死大鼠,截取L4～6段脊髓,分离左右侧脊髓,于-80℃储存.SNI组和对照组各取5只大鼠脊髓,RT-PCR技术扩增nNOS、eNOS和iNOS片段,以β-actin作为内参照,比较SNI组与对照组NOS表达的相对差异.取两组另外5只大鼠脊髓冰上迅速匀浆,均取40 μg的蛋白,分别检测组成型NOS(cNOS,即nNOS和eNOS)和iNOS的活性.结果 SNI组手术侧nNOS、iNOS的mRNA表达均高于SNI组非手术侧和对照组手术侧(P<0.05),而eNOS的表达在SNI组手术侧、非手术侧和对照组手术侧之间差异并无统计学意义.NOS亚型催化活性检测显示SNI组手术侧iNOS和cNOS的活性均高于SNI组非手术侧和对照组手术侧(P<0.05).结论 神经病理性疼痛大鼠模型脊髓背角中iNOS的表达及其合成NO的活性均增加,可能促进了疼痛的发生,nNOS在疼痛中可能具有较强的调节能力.     

Thermal hyperalgesia assessment for rats after spinal cord injury: developing a valid and useful pain index

Background contextOngoing research to understand the mechanism behind pain is heavily dependent on animal testing. However, unlike humans, animal subjects cannot directly communicate with researchers to express the degree of pain they are experiencing. Therefore, measuring the presence of pain in animal studies is based on behavioral tests. The use of arbitrary values for determining the presence of pain in animal studies is an oversimplification of a complex and cortically dependent process.PurposeThe purpose of the present study was to identify a statistically supported latency time indicator that can be used as an accurate index for hyperalgesia to thermal stimuli in Sprague-Dawley rats subjected to T9 contusive spinal cord injury (SCI).Study designA statistical analysis of latency of withdrawal from stimulus-mediated spinal reflex in 979 Sprague-Dawley rats that had been subjected to a T9 contusive SCI was performed.MethodsThis is a retrospective review of a large research database derived from a series of studies performed evaluating thermal hyperalgesia in rats after SCI. Sprague-Dawley rats underwent a T9 contusive SCI and were tested for withdrawal latency from a heat stimulus. Assessment was done preinjury and on Postinjury Days 21, 28, 35, and 42 of the chronic phase of injury via a plantar withdrawal test.ResultsThe baseline test results of the 979 rats showed a significant resemblance to the normal distribution. The observed change in withdrawal showed mean latency drops of 0.42 second (standard error of the mean [SEM], 0.18; p=.026), 0.57 second (SEM, 0.19; p=.004), 0.63 second (SEM, 0.19; p=.002), and 0.69 second (SEM, 0.19; p=.0003). The standard deviation from the mean at all four postsurgical assessments was between 2.8 and 2.9 seconds.ConclusionsInterpretation of withdrawal latency times as a marker for thermal hyperalgesia must be based on an appreciation for the normal distribution of pain scores. Recognizing that withdrawal latency is normally distributed both before and after injury allows for rational assignment of animals to groups designated as hyperalgesic and nonhyperalgesic. Two point nine seconds faster than the mean latency time is a statistically reliable indicator of thermal hyperalgesia in Sprague-Dawley rats subjected to contusive SCI. Repeated testing of animals to establish the presence or absence of thermal hyperalgesia beyond 21 days is not necessary in the absence of intervention.     

Non-opioid pharmacologic treatment of chronic spinal cord injury-related pain

Purpose: Spinal cord injury-related pain is often a severe debilitating condition that adversely affects the patient’s physical health, psychological wellbeing and quality of life. Opioid medications have historically been prescribed to this population with great frequency. As opioid abuse disorder becomes an ever-worsening public health issue, more attention must be placed upon non-opioid options. This paper reviews non-opioid medications to be considered when treating spinal cord injury-related pain. The pertinent literature is reviewed, and the advantages and pitfalls of various medication options are discussed in the complicated context of the individual with a spinal cord injury.Methods: Peer-reviewed journal articles and medication package insert data are reviewed.Results:. The non-opioid medications with the greatest evidence for efficacy in the treatment of chronic spinal cord injury-related pain are drawn from the antiepileptic drug and antidepressant categories though the specific selection must be nuanced to the particular individual patient. More research is required to understand the role of calcitonin, lithium, and marijuana in treating spinal cord injury-related pain.Conclusions: The complex clinical situation of each individual patient must be weighed against the risks and benefits of each medication, as reviewed in this paper, to determine the ideal treatment strategy for chronic spinal cord injury-related pain.     

The relationship between pain and mood following spinal cord injury

Objectives: To explore the relationship between pain and mood during spinal cord injury rehabilitation, and to discuss clinical implications to optimize rehabilitation outcomes.

Design: Repeated measures, retrospective cohort study.

Setting: Tertiary care, spinal cord injury rehabilitation center.

Participants: Patients (N?=?509) who completed both Needs Assessment Checklist (NAC) 1 and NAC2 between February 2008 and February 2015.

Interventions: Not applicable.

Outcome measure: Pain ratings (0–10) and mood scores (0–24) were obtained from the Needs Assessment Checklist (NAC). NAC1 is completed within 4 weeks post-mobilization and NAC2 upon the patient moving to the pre-discharge ward.

Results: There were statistically significant improvements in both pain and mood from NAC1 to NAC2. There were significant correlations between pain and mood at both NAC1 and NAC2 (a decrease in pain was associated with an improvement in mood). Individuals who reported that pain interfered with their rehabilitation had higher pain scores and lower mood scores at both NAC1 and NAC2.

Conclusions: Pain and mood evidently interact following spinal cord injury, and the nature of this relationship is complex. The current study provides some support for the bidirectional causality hypothesis, suggesting that pain and mood exert an effect upon each other. It is important to address pain and psychological issues early and together in the post-injury phase to optimize rehabilitation outcomes.     

Percutaneous peripheral nerve stimulation for treatment of shoulder pain after spinal cord injury: A case report

Context: This describes the first person with spinal cord injury (SCI) treated with percutaneous peripheral nerve stimulation for chronic shoulder pain.

Findings: From baseline to one-week after treatment, the subject's worst pain in the last week, rated on a 0–10 numerical rating scale (BPI-SF3), decreased by 44%. Pain interference decreased and remained below baseline 12 weeks after the end of treatment. There was an associated improvement in the mental component of quality of life.

Conclusion: This case demonstrates the feasibility of treating shoulder pain in patients with SCI with percutaneous PNS. To demonstrate efficacy further studies are required.     

电针对神经病理性疼痛大鼠脊髓P2X3受体表达的影响

目的 探讨电针对神经病理性疼痛大鼠脊髓P2X3受体表达的影响.方法 清洁级雄性SD大鼠60只,体重180 g～220 g,采用随机数字表法分为6组,每组10只:假手术组(Sham组)仅分离坐骨神经,不结扎;神经病理性疼痛组(CCI组)采用坐骨神经慢性压迫性损伤法制备神经病理性疼痛模型;2 Hz穴位电针组(LEA组)于坐骨神经结扎(chronic constrictive injury,CCI)后第4天开始电针治疗,刺激大鼠术侧足三里-阳陵泉穴,频率2 Hz连续波,强度≤1.5 mA,每天1次,30 min/次,连续6d;15 Hz穴位电针组(HEA组)电针频率为15 Hz,余同LEA组;2 Hz非穴位电针组(NA-LEA组)电针刺激大鼠术侧足三里-阳陵泉旁5mm非穴位点,余同LEA组;15 Hz非穴位电针组(NA-HEA组)电针刺激大鼠术侧足三里-阳陵泉旁5mm非穴位点,余同HEA组.各组术前1 d(T0)和术后3、5、7、9 d(T1-4)测定大鼠后肢机械缩足反射阈值(mechanical withdrawal threshold,MWT)和热缩足反射潜伏期(thermal withdrawal latency,TWL);于术后第10天处死大鼠,取右侧L4-6脊髓节段,Western-blot和反转录酶-聚合酶链锁反应法分别检测大鼠脊髓P2X3受体蛋白和mRNA表达.结果 与Sham组比较,其余各组MWT和TWL降低(P＜0.05),脊髓P2X3受体蛋白和mRNA表达升高(P＜0.05);与CCI组比较,LEA组和HEA组T2-4时MWT和TWL升高(P＜0.05),脊髓P2X3受体蛋白和mRNA表达降低(P＜0.05);与LEA组比较,T4时HEA组MWT和TWL升高,脊髓P2X3受体蛋白和mRNA表达增多(P＜0.05).结论 电针足三里-阳陵穴可明显增加神经病理性疼痛大鼠的机械痛和热痛阈值,其机制可能与降低脊髓背角P2X3受体表达有关.     

Differences in resting cerebellar and prefrontal cortical blood flow in spinal cord injury-related neuropathic pain: A brief report

Context: Little is understood about differences in resting neural activity among those with spinal cord injury (SCI)-related neuropathic pain. The purpose of this pilot study was to determine resting cerebral blood flow differences in persons with SCI-related neuropathic pain compared to healthy, pain-free able-bodied controls.Methods: Five persons with paraplegia and ten able-bodied participants were included in this study. Resting blood flow, as measured by a continuous arterial spin labeling (ASL) method of fMRI, was analyzed via statistical parametric mapping.Results: Persons with SCI-related neuropathic pain had significantly lower resting blood flow in the cerebellum (Crus I/II), rostral ventromedial medulla and left insular cortex. In contrast, greater resting blood flow occurred in the medial orbitofrontal cortex among those with SCI-related neuropathic pain compared to controls.Conclusion: Differences in resting blood flow were observed among those with SCI-related pain, particularly in regions that may be involved in affective-motivational and cognitive-evaluative aspects of pain. Larger ASL studies in addition to functional connectivity studies using fMRI are needed to clarify unique neural patterns in this complex and often intractable form of pain.     

神经病理性疼痛大鼠脊髓磷酸化CREB表达的研究

目的研究坐骨神经慢性挤压伤(chronicconstrictioninjury,CCI)后不同时点大鼠脊髓磷酸化cAMP反应成分结合蛋白(p-CREB)含量的变化。方法32只160~180g雄性SD大鼠中,8只为正常对照,其余24只做成CCI模型。用VonFrey细丝测定大鼠后爪触诱发痛的变化,并于术后7、14和30d处死(n=8),取L4~L6脊髓用以免疫印迹(Westernblot)方法测定p-CREB的表达量。结果CCI大鼠结扎侧在术后7、14d出现明显的机械感觉异常(P<0·01),30d后基本消失。与正常大鼠相比,CCI大鼠p-CREB含量在术后7、14d均出现明显升高(P<0·01),术后30d恢复到正常水平。结论CCI大鼠疼痛模型中脊髓p-CREB含量明显增高,并且随疼痛症状消失恢复到正常水平。提示脊髓p-CREB在慢性神经性疼痛中发病机制中有一定的作用。     

脊髓损伤合并截肢患者的康复效果分析

目的:探讨脊髓损伤合并截肢患者的康复治疗效果。方法:1991年～2011年共收治脊髓损伤合并截肢者6例,ASIA分级A级5例,C级1例;右下肢截肢者3例,左下肢截肢者1例,左上肢截肢者1例,右下肢与右上肢截肢者1例,均进行康复评价并确定康复方案。在患者全身情况和残肢关节活动度获得改善后,对截瘫合并下肢截肢者予穿戴假肢和矫形器行站立和行走训练,合并上肢截肢者予佩戴功能性假肢等康复治疗。经过物理治疗(PT)、作业治疗(OT)训练及佩戴相应的假肢和矫形器,并经过反复训练和强化后观察康复效果。应用脊髓损伤神经学分类国际标准(ASIA标准)评估患者神经功能,使用功能独立性评定(FIM)量表评估患者生活自理能力。结果:本组病例平均住院康复时间为126d(58~236d)。5例截瘫患者ASIA神经功能无明显改善(P>0.05),但FIM运动评分显著提高(入院得分为25.83分,出院平均得分为52.17分)(P<0.05)。另1例颈脊髓损伤患者入院为不完全损伤,经过治疗后感觉评分提高58分,运动评分提高14分,FIM评分中自理活动能力提高9分,转移能力提高14分,运动能力提高5分。结论:脊髓损伤合并截肢患者经过佩戴假肢并予综合康复后,患者丧失的部分功能可得到替代,生活自理能力可得到明显提高。     

神经病理性疼痛大鼠脊髓NMDA受体NR2B亚基的表达

目的研究神经病理性疼痛大鼠脊髓背角NR2B亚基表达的改变。方法体重180～200g的雄性SD大鼠随机分为四组（每组10只）：3d（D3）、7d（D7）、14d（D14）组和假手术组。建立外周神经慢性压榨性损伤（CCI）动物模型,假手术组大鼠同样分离坐骨神经,但不结扎神经。各组大鼠分别于术前和术后第3、7、14天及假手术后第3天以Von Frey纤维测定机械痛阈并进行术前术后及组间比较;之后分别于术后第3、7、14天及假手术后第3天断头处死,取患侧L4～L5脊髓背角组织采用Western blot方法测定并比较NR2B亚基的蛋白表达量。结果7d组及14d组大鼠术后机械痛阈均明显低于假手术组（P〈0．05）;其患侧脊髓背角NR2B蛋白表达量明显高于假手术组（P〈0．05）。3d组大鼠术后机械痛阈及患侧脊髓背角NR2B蛋白表达量与假手术组相比差异无统计学意义。结论神经病理性疼痛大鼠的脊髓背角的NR2B蛋白表达水平较假手术组显著升高,此蛋白表达水平的升高可能是导致大鼠神经病理性疼痛的原因之一。     

The effect of repetitive transcranial magnetic stimulation on refractory neuropathic pain in spinal cord injury

Objective

To investigate the analgesic effect of repetitive transcranial magnetic stimulation (rTMS) on intractable neuropathic pain in patients with spinal cord injury (SCI).

Design

A single center, prospective, randomized, double-blinded, controlled study.

Setting

SCI rehabilitation unit of university rehabilitation center.

Participants

Seventeen patients with SCI and chronic neuropathic pain who met the inclusion criteria recruited between April 2010 and January 2012.

Interventions

Ten daily treatment sessions of real or sham rTMS (30 trains of 10-Hz stimuli for a duration of 5 seconds; a total of 1500 pulses at intensity equal to 110% of the resting motor threshold) was applied over vertex using a figure-of-8-shaped coil.

Outcome measures

Pain was assessed with visual analog scale (VAS) at baseline and 10 days, 6 weeks and 6 months after the treatment. Patients’ satisfactions obtained using a 5-point Likert scale at 6 months.

Results

Both real and sham rTMS provided a significant reduction in the VAS scores (real rTMS group, P = 0.004; sham rTMS group, P = 0.020). Post hoc analysis revealed the significant difference was at 10 days and 6 weeks compared to baseline in the real rTMS group and only at 10 days compared to baseline in the sham rTMS group. Comparison of VAS scores and patient satisfaction did not show any significant difference at each assessment point (P > 0.05).

Conclusion

Our results demonstrated analgesic effect of rTMS on intractable neuropathic pain in SCI was not superior to placebo. However, middle-term (over 6 weeks) pain relief by rTMS is encouraging and suggests the need for future studies with a larger sample size.     

桔梗皂苷D对大鼠神经病理性疼痛及脊髓小胶质细胞活化的影响

目的:探讨桔梗皂苷D（platycodin D, PD）对大鼠神经病理性疼痛模型的镇痛作用及其对脊髓小胶质细胞活化的影响。方法:将60只雄性成年SD大鼠按随机数字表法分为6组（每组10只）：假手术组（Sham组）、脊神经结扎（spinal nerve ligation, SNL）组（SNL组）、SNL+生理盐水组（SN...     

步行矫形器在脊柱脊髓损伤患者康复中的应用初探

目的：探讨步行矫形器配合综合康复治疗在完全性脊髓损伤患者康复中的效果。方法：13例完全性脊髓损伤患者，男10例，女3例，其中C7 1例、T4 1例、T6 1例、T10～L1 10例；年龄21～41岁，平均33．2岁；在装配步行矫形器前进行强化康复治疗，包括肌肉力量、心肺功能、转移、日常活动能力（ADL）、膀胱功能等，矫形器装配后配合步态步行训练；分别于矫形器装配前和出院前应用限时的步行功能检查（包括6min步行评测和10m步行时间评测）、步态分析及改良Barthel指数（MBI）作为指标进行评定。结果：13例患者矫形器装配及训练后10m步行时间平均55．2s，6min步行距离为74．9m，平均步长37．9cm；12例应用往复式截瘫步行器（RGO）可作功能性步行，1例四肢瘫患者借助ARGO可作治疗性步行；训练后ADL能力明显改善，MBI评分平均提高31．5分。结论：步行矫形器配合系统的康复治疗对改善完全性脊髓损伤患者步行能力及ADL效果理想。