巨噬细胞在神经病理性疼痛中的作用

神经病理性疼痛（neuropathic pain, NP）是指由躯体感觉系统的损害或疾病导致的疼痛。NP的发病机制复杂,与免疫调节有关。巨噬细胞是体内重要的免疫细胞,在体内通过自身极化和神经免疫相互作用参与神经损伤后的外周及中枢敏化形成过程,促进NP的发展。文章对巨噬细胞在NP中的作用进行综述,研究巨噬细胞在NP形成与...     

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。     

重复经颅磁刺激治疗脊髓损伤后神经病理性疼痛的系统综述和荟萃分析

目的 系统分析重复经颅磁刺激(repetitive transcranial magnetic stimulation, rTMS)治疗脊髓损伤后神经病理性疼痛(neuropathic pain, NP)的临床效果。方法 计算机检索中国知网、万方数据库、维普、PubMed、Embase、Corchrane Library、Web of science等中英文数据库,检索rTMS治疗脊髓损伤后NP的随机对照研究,采用Jadad量表进行质量评价后进行Meta分析。结果 共纳入6篇文献。合并Meta分析显示,rTMS可显著降低脊髓损伤后NP患者的VAS/NRS水平(MD=-1.03,95%CI=-1.60～-0.46,P<0.01);rTMS可降低脊髓损伤后NP患者的HAMD评分(MD=-1.71,95%CI=-2.60～-0.82,P<0.01);rTMS对脊髓损伤后NP患者的HAMA评分影响不显著(MD=-0.84,95%CI=-5.48～3.81,P=0.72)。结论 rTMS可缓解脊髓损伤后NP患者的疼痛程度,改善患者的抑郁状态。     

神经病理性疼痛病因及其机制研究进展

神经病理性疼痛是神经系统损伤引起的一种慢性状态，国际疼痛研究协会称之“来源于或者由神经系统的功能紊乱引起”，包括确切存在的神经损伤，比如神经缺血或其他病变，也包括缺少确切损伤状态下的疼痛，比如复合区域性疼痛综合征Ⅰ型和某些三叉神经痛。急性疼痛对机体具有警示和“保护”作用，而神经病理性疼痛与之不同，它可以持续存在，对机体无益，甚至会严重影响生活质量。其自发的疼痛，可以描述为针刺、电灼、撕裂、刀割样疼痛，也可表现为诱发的疼痛，被称作感觉异常和痛觉过敏。     

鞘内注射Roscovitine缓解大鼠慢性神经病理性疼痛

目的 在SD大鼠脊髓后根神经节慢性压迫(CCD)模型上观察鞘内注射Roscovitine的镇痛效果.方法 用不锈钢棒(长4 mm,直径0.7 mm)持续件压迫脊髓背根神经节(DRG)建立慢性神经病理性疼痛模型.术后第7天鞘内注射溶解于DMSO 10 μl中的Roscovitine 50 μg(R组);同时设CCD术后第7天只给予鞘内注射二甲基亚砜(DMS0)10 μl的CCD组(C组)和非CCD处理、并给予鞘内注射DMSO 10 μl的假手术组(S组).三组均于CCD术前、术后第7天(给药前)及给药后2、24、72 h榆测机械痛缩足阈值(PWMT)和热痛缩足潜伏期(PWTL).CCD术前及给药后72 h用免疫组化技术检测脊髓背角N-甲基-D天冬门氨酸(NMDA)受体2A亚基(NR2A)的表达水平.结果 R组和C组给药前PWMT均较术前显著降低[(3.64±0.40)g vs.(14.38±1.53)g,(3.50±0.77)g vs(13.25±2.21)g],也明显低于S组的(11.31±1.13)g(P<0.05).R组和C组给药前PWTL均较术前显著缩短[(9.28±1.18)s vs(18.34±1.23)s,(8.91±1.08)s vs.(18.59±1.92)s],也短于S组的(18.45±1.44)s(P<0.05).R组PWMT在给药后24 h较给药前和C组显著增加[(7.32±0.69)g vs.(3.64±0.40)g,(3.86±1.14)g](P<0.05),而给药后2 h PWTL,较给药前和C组显著延长[(15.464±1.51)s vs.(9.28±1.18)s,(9.91±1.07)s(P<0.05).给药后72 h,R组脊髓背角NR2A受体表达水平明显低于C组[(0.21±0.02)vs.(0.26±0.01)](P<0.05).结论 鞘内注射Roseovitine能有效改善CCD大鼠痛行为学反应;其作用可能与抑制脊髓背角NR2A受体表达有关.     

细胞因子和胶质细胞在神经病理性疼痛中的作用

在神经病理性疼痛的机制研究中,许多学者发现神经免疫及神经系统炎症反应是造成疼痛的重要原因之一.其中,细胞因子和胶质细胞激活在疼痛的产生和维持中起到非常重要的作用.因而它们有可能成为治疗神经病理性疼痛的新的靶点.     

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.     

白介素和神经病理性疼痛

近来实验发现免疫细胞活化对于人类和实验动物神经病理性疼痛的病因和症状有密切联系,而免疫细胞活化的一类产物--白介素在疼痛形成和维持过程中发挥重要作用.此文讨论白介素-1(白介素-1α、白介素-1β、白介素-1ra)、白介素-6和白介素-10在神经病理性疼痛的产生和维持过程的作用,探讨白介素在神经病理性疼痛治疗的前景.     

脊髓神经元和胶质细胞激活在三种神经病理性疼痛大鼠模型脊髓水平致痛机制中的作用

目的比较脊髓神经元和胶质细胞(星形胶质细胞和小胶质细胞)激活在三种大鼠神经病理性疼痛模型脊髓水平致痛机制中的作用。方法 SD 大鼠24只,体重150g～200g,随机分为4 组,每组6只,分别为对照组、CCI 组、SNL 组和 SNI 组。对照组不实施手术；CCI、SNL、SNI 组分别于左侧制作慢性坐骨神经缩窄损伤模型(CCI)、脊神经结扎模型(SNL)和保留性脊神经损伤模型(SNI)。术前3d 至术后15d 隔日使用机械刺激测定术侧后爪50%缩爪阈值。术后15d 测痛后,用多聚甲醛灌注大鼠,取L_(5,6)脊髓,进行免疫组化实验；用抗原癌基因蛋白 c-Fos、星形胶质细胞标记蛋白(GFAP)和小胶质细胞标记蛋白(OX-42)抗体分别检测神经元、星形胶质细胞和小胶质细胞的激活状况。结果术后7d CCI、SNL、SNI 组术侧50%缩爪阈值均达到最低值,并维持至术后15d；术后15d,对照组、CCI 组、SNL 组和 SNI 组50%缩爪阈值分别为14.1±1.5、2.6±0.5、1.5±0.6、(0.8±0.4)g,大小顺序依次为对照组、CCI 组、SNL 组、SNI 组(P＜0.05)。与对照组比较,CCI、SNL 和 SNI 组Ⅳ～Ⅵ层 c-Fos 阳性神经元数量增加,脊髓背角Ⅰ或Ⅱ层星形胶质细胞及Ⅰ～Ⅳ层小胶质细胞的激活状态升高(P＜0.05), 但 CCI、SNL 和 SNI 组间脊髓背有Ⅳ～Ⅵ层 c-Fos 阳性神经元数量、术侧脊髓背角Ⅰ或Ⅱ层星形胶质细胞的及Ⅰ～Ⅳ层小胶质细胞激活状态差异无统计学意义(P＞0.05)。结论三种神经病理性疼痛大鼠模型中脊髓背角神经元、星形胶质细胞和小胶质细胞的激活状况一致,提示其在脊髓水平致痛机制相似。     

T型钙通道在大鼠神经病理性疼痛维持中的作用

目的观察鞘内注射T型钙通道阻滞剂米贝地尔对慢性背根神经节压迫（CCD）大鼠机械痛敏和热痛敏的影响，探讨T型钙通道在脊髓水平神经病理性疼痛维持中的作用。方法鞘内置管成功的SD大鼠48只，随机分为6组（n=8）：假手术组（Ⅰ组）、CCD组（Ⅱ组）、CCD＋生理盐水组（Ⅲ组）、CCD＋米贝地尔50μg组（Ⅳ组）、CCD＋米贝地尔100μg组（V组）、CCD＋米贝地尔200μg组（Ⅵ组）。鞘内置管后5d制备CCD模型，Ⅲ～Ⅵ组在CCD后5d，分别鞘内单次注射米贝地尔50、100、200μg 10μl。记录大鼠机械缩足反射阈值和热缩足潜伏期。结果Ⅱ组从CCD后1～21d形成了机械痛敏和热痛敏；鞘内注射米贝地尔50、100、200μg减轻了CCD诱导机械痛敏和热痛敏。结论T型钙通道在脊髓水平参与了神经病理性疼痛的维持。     

Shoulder pain and functional disability in spinal cord injury patients

Sixty spinal cord injured patients were examined to determine the incidence of nontraumatic shoulder pain and associated functional disability during the first 18 months after spinal cord injury (SCI). Seventy-eight percent of quadriplegics and 35% of paraplegics had pain in the first six months. When reexamined six to 18 months after SCI, 33% of the quadriplegics and 35% of the paraplegics continued to have pain. The functional disability resulting from shoulder pain was not a significant problem for the paraplegics; however, 84% of the quadriplegics having pain had either moderate or severe functional disability during the first six months after SCI, and this impairment persisted in patients with shoulder spasticity at follow-up evaluation between six and 18 months postinjury.     

Calcitonin for acute neuropathic pain associated with spinal cord injury

Neuropathic pain associated with spinal cord injury is caused by complex neural mechanisms and is often refractory to standard therapy. Salmon calcitonin was an effective treatment for neuropathic symptoms in this case series of three patients with recent spinal cord injury. Salmon calcitonin is already used to help manage pain after limb amputation and also after vertebral fractures and it is perhaps surprising that it has not been trialled previously for spinal cord injury pain. Calcitonin is thought to exert its effect by modulation of the serotonergic system and is generally well tolerated and convenient to administer. This underutilised drug may be a very useful adjuvant for neuropathic pain associated with spinal cord injury.     

Effects of smoking on neuropathic pain in two people with spinal cord injury

BACKGROUND/OBJECTIVE: To describe an apparent relationship between smoking and the neuropathic pain experience in people with spinal cord injury (SCI). METHOD: Case Reports. PARTICIPANTS/METHODS: Two individuals treated at a rehabilitation center. The first was a 38-year-old white man with a T1 2 SCI, American Spinal Injury Association (ASIA) impairment scale (AIS) A, secondary to motor vehicle crash. Duration of injury was 14 years. He reported burning pain in his legs, and has smoked 1/2 pack per day for the last 15 years. The second was a 55-year-old African American man with a T6 SCI, AIS A, secondary to gunshot wound. Duration of injury was 22 years. He was a 40-year 1/2 to 1 pack per day smoker, who, after injury, consistently experienced burning, radicular pain, rated 7/10, around the level of the injury. SUMMARY: The first subject rated his pain as 4/10 when not smoking and 7/10 when smoking. The pain subsided 30 minutes after smoking was discontinued. He noted an immediate increase in neuropathic pain when smoking. The second subject quit smoking for 1 month and immediately noted that the pain disappeared, rating it 0/10. After he resumed smoking, his radicular pain was 8.5/10 in the morning and 5/10 in afternoon. CONCLUSIONS: No similar reports have been published, based on a MEDLINE search. Nicotinic receptors have been implicated in pain perception. It is unclear to what extent these 2 cases generalize to the SCI population. We plan to explore this via survey and experimental research. Smoking cessation may have a dual benefit of increased health and decreased neuropathic pain.     

Antinociceptive effect of riluzole in rats with neuropathic spinal cord injury pain

Symptoms of neuropathic spinal cord injury (SCI) pain include cutaneous hypersensitivity and spontaneous pain below the level of the injury. Riluzole, an FDA-approved drug for the treatment of amyotrophic lateral sclerosis, has been demonstrated to attenuate neural excitotoxicity by blocking the effects of the excitatory amino acid glutamate on glutamate receptors and by inhibiting voltage-gated Na(+) and Ca(2+) channels. Neuropathic pain in rat models of SCI is thought to be mediated by dysfunctional ion channels and glutamate receptors expressed on CNS neurons. Thus riluzole's mechanism of action could be relevant in treating neuropathic SCI pain. The current study evaluated the antinociceptive potential of riluzole in rats following a SCI. Four weeks after a brief compressive injury to the mid-thoracic spinal cord, rats displayed significantly decreased hind paw withdrawal thresholds, suggestive of below-level cutaneous hypersensitivity. A single systemic dose of riluzole (8?mg/kg) injected intraperitoneally (i.p.) reversed cutaneous hypersensitivity in SCI rats. To identify riluzole's CNS site of action, riluzole was injected intrathecally (i.t.) and intracerebroventricularly (i.c.v.) in SCI rats. Significant antinociceptive effects were obtained following i.c.v., but not i.t., injection. Systemic riluzole was also antinociceptive in uninjured rats, increasing the latency to respond to an acute noxious thermal stimulus in the tail flick test. Unlike in SCI rats, however, riluzole was not effective when administered directly into the CNS, indicating a peripherally mediated antinociceptive mechanism. Although riluzole appears to have a general antinociceptive effect, the site of action may be model dependent. In total, these data indicate that riluzole may be an effective clinical analgesic for the treatment of below-level neuropathic SCI pain. Although the exact mechanism of action is not clear, there is a predominant supraspinal component of riluzole-induced antinociception in SCI rats.     

Priorities of desired functional recovery in Indian spinal cord injury patients

BackgroundSpinal cord injuries (SCI) affect various functions and therefore the Quality of life (QOL) of these patients. Regaining even partial function can lead to improved QOL; making it crucial to know which functions are most important for these patients.Material and methodsThis prompted us to conduct a survey in which subjects were asked to rank seven functions in order of importance to improve their quality of life. Survey was administered by personal interview of patients in different spinal injury rehabilitation centers across India.ResultsA total of 112 patients completed the survey. Regaining arm and hand function was ranked as first priority by quadriplegics while bowel/bladder function and walking movements were ranked as 2nd and 3rd priority. Paraplegics ranked return of walking movements as their first priority, bladder/bowel recovery as second and trunk strength/sexual function as 3rd priority.ConclusionThis knowledge empowers us to focus our research on what is most important for their QOL.     

Electroencephalographic slowing and reduced reactivity in neuropathic pain following spinal cord injury

STUDY DESIGN: Brain wave activity in people with paraplegia, with and without neuropathic pain, was compared to brain wave activity in matched able-bodied controls. OBJECTIVES: To investigate whether spinal cord injury with neuropathic pain is associated with a slowing of brain wave activity. SETTING: Australia. METHODS: Electroencephalographic (EEG) data were collected in the eyes open (EO) and eyes closed (EC) states from 16 participants with paraplegia (eight with neuropathic pain and eight without pain) and matched able-bodied controls. Common EEG artefacts were removed using independent component analysis (ICA). Peak frequency in the theta-alpha band and EEG power in the delta, theta, alpha and beta frequency bands were compared between groups. RESULTS: The results show significant slowing of the EEG in people with neuropathic pain, consistent with the presence of thalamocortical dysrhythmia (TCD). Furthermore, people with neuropathic spinal cord injury (SCI) pain had significantly reduced EEG spectral reactivity in response to increased or decreased sensory input flowing into the thalamocortical network, as modulated by the eyes open and eyes closed states. CONCLUSION: The results provide further evidence for alterations in brain electric activity that may underlie the development of neuropathic pain following SCI.     

Neurological and functional recovery after thoracic spinal cord injury

Objective

To describe neurological and functional outcomes after traumatic paraplegia.

Design

Retrospective analysis of longitudinal database.

Setting

Spinal Cord Injury Model Systems.

Participants

Six hundred sixty-one subjects enrolled in the Spinal Cord Injury Model Systems database, injured between 2000 and 2011, with initial neurological level of injury from T2–12. Two hundred sixty-five subjects had second neurological exams and 400 subjects had Functional Independence Measure (FIM) scores ≥6 months after injury.

Outcome Measures

American Spinal Injury Association Impairment Scale (AIS) grade, sensory level (SL), lower extremity motor scores (LEMS), and FIM.

Results

At baseline, 73% of subjects were AIS A, and among them, 15.5% converted to motor incomplete. The mean SL increase for subjects with an AIS A grade was 0.33 ± 0.21; 86% remained within two levels of baseline. Subjects with low thoracic paraplegia (T10–12) demonstrated greater LEMS gain than high paraplegia (T2–9), and also had higher 1-year FIM scores, which had not been noted in earlier reports. Better FIM scores were also correlated with better AIS grades, younger age and increase in AIS grade. Ability to walk at 1 year was associated with low thoracic injury, higher initial LEMS, incomplete injury and increase in AIS grade.

Conclusion

Little neurological recovery is seen in persons with complete thoracic SCI, especially with levels above T10. Persons who are older at the time of injury have poorer functional recovery than younger persons. Conversion to a better AIS grade is associated with improvement in self-care and mobility at 1 year.