Mechanisms of neuropathic pain in patients with Charcot-Marie-Tooth 1 A: A laser-evoked potential study

Charcot-Marie-Tooth (CMT) disease is the most common inherited neuropathy. The CMT1A type can be considered the typical phenotype of this disease. Although pain is not considered a relevant symptom in CMT patients by physicians and no study assessed it comprehensively, this symptom is frequently complained by patients. The objective of the present study was to investigate the nociceptive system in a sample of CMT1A patients suffering from pain by laser-evoked potentials (LEPs). Moreover, we also used a pain specific questionnaire in order to obtain patient-oriented data about their painful symptoms, the Neuropathic Pain Diagnostic Questionnaire (DN4). We evaluated 16 patients affected by CMT1A and 14 controls. All subjects underwent a standard LEP recording session (foot, hand, and face stimulation) and filled in the DN4. While the N2/P2 amplitude to foot stimulation was lower in CMT patients than in controls (p = 0.003), no difference in LEP amplitude to both hand and face stimulation was found between patients and healthy subjects (p > 0.05). This result is probably due to a length-dependent Aδ-fiber loss which involves mostly the longer fibers coming from the lower limb. In our patients, there was a significant association between a reduced N2/P2 amplitude to foot stimulation and a high DN4 score (p = 0.03), meaning that patients with highly probable neuropathic pain had also low N2/P2 amplitude values to painful foot stimulation. This suggests that in our CMT1A patients neuropathic pain is probably related to a reduction of the Aδ afferents.     

脊髓损伤患者神经病理性疼痛现况调查及相关影响因素分析

目的 调查脊髓损伤患者神经病理性疼痛（NP）现况,并分析其相关影响因素。 方法 先用DN4量表在所有诊断为脊髓损伤的患者中筛选出伴有NP的患者,搜集70例脊髓损伤伴NP患者的性别、年龄、文化程度、职业、平均月收入、损伤部位、婚姻状态等一般调查资料,然后再对筛选出来的患者用简化的McGill疼痛问卷表（SF-MPQ）进行NP现况调查,记录患者的疼痛目测类比法（VAS）评分以及疼痛评级指数(PRI),包括PRI-感觉项、PRI-情感项及PEI等平均得分;采用SPSS13.0统计软件对患者的基本资料进行单因素和多因素统计分析,分析患者NP的影响因素。 结果 ①患者的平均疼痛目测类比法（VAS）评分4.37分;SF-MPQ调查的平均PRI得分8.23分,PRI-感觉项平均得分5.2 3分,PRI-情感项平均得分3.00分;现在疼痛强度(PPI)平均程度为1.86,PPI介于轻痛和难受之间,PPI中出现最多的是难受这个描述词。疼痛描述词按出现频率排在前三位的是刺痛、烧灼痛和坠胀痛。有60例（85.7%）患者认为疼痛对其情感状态造成影响,出现最多的是疲惫耗竭感这个描述词。②单因素分析显示损伤程度、文化程度、婚姻状况、家庭人均月收入、家人支持与否以及是否用药是NP的影响因素（P<0.01）,而性别、年龄、病程、损伤部位、职业等因素与VAS评分无明显相关性（P>0.05）;多因素Logistic回归分析显示,未婚、损伤程度重为NP的独立保护因素（OR＜1）,家庭人均月收入低、没有家人支持、没有用药为NP的独立危险因素（OR＞1）。 结论 脊髓损伤患者NP感觉多样,疼痛程度中等,绝大多数患者情感状态受到影响;未婚和损伤程度重为独立保护因素,家庭人均月收入低、没有家人支持及没有用药为其独立危险因素。     

Migraine headaches and pain with neuropathic characteristics: Comorbid conditions in patients with multiple sclerosis

We conducted a postal survey to assess the prevalence and characteristics of neuropathic pain and migraine in a cohort of multiple sclerosis (MS) patients. Of the 1300 questionnaires sent, 673 could be used for statistical analysis. Among the respondents, the overall pain prevalence in the previous month was 79%, with 51% experiencing pain with neuropathic characteristics (NCs) and 46% migraine. MS patients with both migraine and NC pain (32% of the respondents) reported more severe pain and had lower health-related quality of life than MS patients with either migraine or NC pain. Pain intensity in MS patients with migraine was moderate (6.0 ± 0.1). Migraine was mostly episodic, but headaches were occurring on ?15 days per month in 15% of those with migraine. MS patients with migraine were younger and had shorter disease durations than those with NC pain. NC pain was most often located in the extremities, back and head, and was frequently described as tingling and pins-and-needles. The intensity of NC pain was low to moderate (4.9 ± 0.1), but positively correlated with the number of painful body sites. Nonetheless, patients with NC pain were more disabled (with a higher Expanded Disability Status Scale and pain interference index) than patients with migraine. Migraine, but not NC pain, was associated with age, disease duration, relapsing-remitting course, and interferon-beta treatment. This suggests that NC pain and migraine are mediated by different mechanisms. Therefore, pain mechanisms that specifically operate in MS patients need to be characterized to design optimal treatments for these individuals.     

An investigation to determine the association between neck pain and upper limb disability for patients with non-specific neck pain: a secondary analysis

This study investigated the relationship between neck pain and upper limb disability in patients with non-specific neck pain (n = 151) recruited from physiotherapy departments in the United Kingdom. Baseline neck pain/disability was measured using the Northwick Park Neck Pain Questionnaire (NPQ). Baseline upper limb disability was measured using the Disabilities of Arm, Shoulder, Hand questionnaire (DASH). A range of baseline psychosocial variables were measured as potential confounding variables. Pairwise analysis revealed a positive correlation between NPQ score and DASH score (Pearsons’ r = 0.799, p < 0.001). After adjusting for potential confounding variables, stepwise linear regression indicated that increasing upper limb disability was predicted by two baseline variables: higher NPQ scores (B = 0.743) and lower pain self efficacy (PSE) scores (B = −0.489) {R² = 0.713; n = 100, p < 0.001}. This study provides preliminary evidence that patients with severe neck pain/disability also report severe upper limb disability. The relationship between neck pain/disability and upper limb disability was mediated by PSE. Clinically, the presence of severe neck pain or low PSE should direct clinicians towards an assessment of upper limb function. In these cases upper limb disability may need to be addressed as part of the neck management process.     

Prevalence and aetiology of neuropathic pain in cancer patients: a systematic review

Pain in cancer patients remains common and is often associated with insufficient prescribing of targeted analgesia. An explanation for undertreatment could be the failure to identify neuropathic pain mechanisms, which require additional prescribing strategies. We wanted to identify the prevalence of neuropathic mechanisms in patients with cancer pain to highlight the need for detailed assessment and to support the development of an international classification system for cancer pain. We searched for studies that included adult and teenage patients (age above 12 years), with active cancer and who reported pain, and in which a clinical assessment of their pain had been made. We found 22 eligible studies that reported on 13,683 patients. Clinical assessment methods varied, and only 14 studies reported confirmatory testing for either sensory abnormality or diagnostic lesion to corroborate a diagnosis of neuropathic pain. We calculated that the prevalence of patients with neuropathic pain (95% confidence interval) varied from a conservative estimate of 19% (9.4% to 28.4%) to a liberal estimate of 39.1% (28.9% to 49.5%) when patients with mixed pain were included. The prevalence of pain with a neuropathic mechanism (95% confidence interval) ranged from a conservative estimate of 18.7% (15.3% to 22.1%) to a liberal estimate of 21.4% (15.2% to 27.6%) of all recorded cancer pains. The proportion of pain caused by cancer treatment was higher in neuropathic pain compared with all types of cancer pain. A standardised approach or taxonomy used for assessing neuropathic pain in patients with cancer is needed to improve treatment outcomes.     

Investigation of neuropathic pain in treated leprosy patients in Ethiopia: a cross-sectional study

Pain can be a significant problem for treated leprosy patients. It can be nociceptive due to tissue inflammation occurring during episodes of immune mediated reactions, or neuropathic due to leprosy affecting the somatosensory system. There are sparse epidemiological data on the prevalence and impact of neuropathic pain in treated leprosy patients. Tools for assessing neuropathic pain have not been validated in leprosy. We have examined nature of pain in a cross-sectional study to determine the prevalence of neuropathic pain (NP) in 80 recently treated leprosy patients in Ethiopia. Pain and depression were evaluated using the General Health Questionnaire (GHQ-12) and the Brief Pain Inventory (BPI) questionnaire. The Douleur Neuropathique en 4 Questions (DN4) and the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) were used as screening tools for NP. Pain of any type was experienced by 60% of the patients. Pure nociceptive pain was experienced by 43%, pure NP by 11%, and mixed pain by 6%. Of the 14 patients who had NP either alone or in combination with nociceptive pain, 12 had high GHQ-12 scores, indicating possible depression. The DN4 had sensitivity and specificity of 100% and 45%, whereas the LANSS had 85% and 42%, respectively. This is the first study to differentiate nociceptive from NP in leprosy patients. The prevalence of NP is high in recently treated Ethiopian leprosy patients. We have validated the use of DN4 in leprosy and it is easier to use than LANSS. Depression is a common co-morbidity in patients with NP. The high prevalence and morbidity of NP in treated leprosy patients warrant clinical trials to assess the efficacy of pain therapies for leprosy-associated NP.     

护理指导改善神经病理性疼痛患者药物依从性研究

目的探讨护理指导改善神经病理性疼痛患者服用阿片类药物的依从性。方法选择2010年3—9月在上海交通大学附属第六人民医院门诊疼痛科就诊的神经病理性疼痛患者90例,随机分为干预组和对照组各45例。干预组给予曲马多缓释片后进行4周护理指导,对照组给予曲马多缓释片后常规宣教。比较干预组和对照组给药1周、2周、3周及4周后疼痛变化、不良反应情况及患者对药物依从性程度。结果两组患者在给药1周、2周、3周及4周后疼痛情况较给药前均明显改善,第1周两组间疼痛比较差异无统计学意义(P>0.05);第2～4周时,对照组患者的疼痛高于干预组,两组比较差异有统计学意义(P<0.01)。两组患者在给药1周后均出现不良反应,差异无统计学意义(P>0.05),给药2～4周后对照组不良反应加重,与干预组比较差异有统计学意义(P<0.01)。给药1周时两组患者对镇痛药物的依从性高,差异无统计学意义(P>0.05),给药后2～4周,干预组对镇痛药物的依从性明显高于对照组(P<0.01)。结论护理指导可以减轻阿片类药物治疗神经病理性疼痛的不良反应,提高患者对镇痛药物的依从性,有效控制疼痛,提高患者的生活质量。     

The effect of venlafaxine on ongoing and experimentally induced pain in neuropathic pain patients: a double blind, placebo controlled study.

BACKGROUND AND AIM: The aim of this randomized double blind placebo controlled study was to investigate the effectiveness and the safety of venlafaxine XR 75 and 150 mg on ongoing pain and on quantitative sensory tests in 60 patients with neuropathic pain for 8 weeks. METHODS: Evaluation parameters consisted of ongoing pain intensity (VAS), patient satisfaction, side effects, global efficacy and tolerance. Quantitative sensory measurements taken from the affected area before and after the drug treatment included pin-prick hyperalgesia, allodynia, detection and pain thresholds to electrical and heat stimuli, temporal summation of repetitive electrical and heat stimuli. RESULTS: A total of 55 patients completed the study. VAS scores decreased significantly compared to the baseline measurements in all groups. There was no significant difference between the groups regarding pain intensity and escape medication. The areas of allodynia and pin-prick hyperalgesia decreased significantly in venlafaxine groups compared to the placebo. There was no significant difference between the groups regarding the detection thresholds (electrical and heat). The pain threshold and the summation threshold to electrical stimuli and the summation threshold to heat stimuli increased significantly following treatment in both venlafaxine groups. In addition, the degree of the temporal summation to electrical and heat stimuli decreased significantly following treatment in both venlafaxine groups compared to the placebo. CONCLUSION: The study showed significant effect of venlafaxine in the manifestations of hyperalgesia and temporal summation, but not on the ongoing pain intensity. Furthermore, the quantitative sensory tests provided complementing information to the clinical measures.     

普瑞巴林治疗神经病理性疼痛的疗效与安全性分析

目的：探讨普瑞巴林治疗神经病理性疼痛的疗效其安全性。方法将58例神经病理性疼痛患者随机分为普瑞巴林组和卡马西平组各29例,分别给予普瑞巴林和卡马西平治疗,所有入组患者均在治疗前及治疗1、2、3、4周时应用疼痛视觉模拟评分法（VAS）、睡眠干扰评分法、汉密尔顿抑郁量表（HAMD）及汉密尔顿焦虑量表（HAMA）进行疗效评定,同时观察两组不良反应情况。结果两组患者治疗后VAS评分、睡眠干扰评分、HAMD、HAMA评分较治疗前均有所降低（P＜0.05）;相同治疗时间内普瑞巴林组比卡马西平组评分降低明显（P＜0.05）;治疗过程中普瑞巴林组不良反应发生率较卡马西平组低（P＜0.05）。结论普瑞巴林治疗神经病理性疼痛疗效好,不良反应发生率低。     

Hemiplegic shoulder pain: Evidence of a neuropathic origin

Hemiplegic shoulder pain (HSP) is common after stroke. Whereas most studies have concentrated on the possible musculoskeletal factors underlying HSP, neuropathic aspects have hardly been studied. Our aim was to explore the possible neuropathic components in HSP, and if identified, whether they are specific to the shoulder or characteristic of the entire affected side. Participants included 30 poststroke patients, 16 with and 14 without HSP, and 15 healthy controls. The thresholds of warmth, cold, heat-pain, touch, and graphesthesia were measured in the intact and affected shoulder and in the affected lower leg. They were also assessed for the presence of allodynia and hyperpathia, and computed tomography/magnetic resonance imaging scans of the brain were reviewed. In addition, chronic pain was characterized. Participants with HSP exhibited higher rates of parietal lobe damage (P < 0.05) compared to those without HSP. Both poststroke groups exhibited higher sensory thresholds than healthy controls. Those with HSP had higher heat-pain thresholds in both the affected shoulder (P < 0.001) and leg (P < 0.01), exhibited higher rates of hyperpathia in both these regions (each P < 0.001), and more often reported chronic pain throughout the affected side (P < 0.001) than those without HSP. The more prominent sensory alterations in the shoulder region suggest that neuropathic factors play a role in HSP. The clinical evidence of damage to the spinothalamic-thalamocortical system in the affected shoulder and leg, the presence of chronic pain throughout the affected side, and the more frequent involvement of the parietal cortex all suggest that the neuropathic component is of central origin.     

Prevalence of chronic pain with neuropathic characteristics in the general population

We conducted a large nationwide postal survey to estimate the prevalence of chronic pain with or without neuropathic characteristics in the French general population. A questionnaire aimed at identifying chronic pain (defined as daily pain for at least 3 months), evaluating its intensity, duration and body locations, was sent to a representative sample of 30,155 subjects. The DN4 questionnaire was used to identify neuropathic characteristics. Of the questionnaires, 24,497 (81.2%) were returned and 23,712 (96.8%) could be assessed. Seven thousand five hundred and twenty-two respondents reported chronic pain (prevalence=31.7%; [95%CI: 31.1-32.3]) and 4709 said the pain intensity was moderate to severe (prevalence=19.9%; [95%CI: 19.5-20.4]). Neuropathic characteristics were reported by 1631 respondents with chronic pain (prevalence=6.9%; [95%CI: 6.6-7.2]), which was moderate to severe in 1209 (prevalence=5.1% [95%CI: 4.8-5.4]). A higher prevalence of chronic pain with neuropathic characteristics was associated with middle age (50-64 years), manual professions and those living in rural areas. It was more frequently located in the lower limbs and its intensity and duration were higher in comparison with chronic pain without neuropathic characteristics. This large national population-based study indicates that a significant proportion of chronic pain patients report neuropathic characteristics. We identified distinctive socio-demographic profile and clinical features indicating that chronic pain with neuropathic characteristics is a specific health problem.     

不同频率的高频重复经颅磁刺激对大鼠神经病理性疼痛的影响

目的观察高频重复经颅磁刺激(rTMS)对神经病理性疼痛模型大鼠的影响,并比较3种不同频率的rTMS对神经病理性疼痛的治疗效果,探索最佳治疗频率。方法选取健康成年雄性SD大鼠100只,随机分为假手术组、模型组、rTMS组、假刺激组,rTMS组又分为5 Hz组、10 Hz组、20 Hz组。于造模成功后第3天开始进行为期5 d或10 d的rTMS治疗。分别于术前、术后不同时间点对各组大鼠进行疼痛行为学评分,包括热痛敏缩足潜伏时(PWTL)、机械痛敏缩足阈值(PWMT)。结果治疗后各rTMS组的PWTL和PWMT值均较模型组不同程度增加,且10 Hz组、20 Hz组的PWTL、PWMT值增加较5 Hz组更明显,10 Hz和20 Hz组间的PWTL和PWMT值比较,差异无统计学意义(P>0.05)。结论不同频率rTMS治疗神经病理性疼痛的疗效不同,10 Hz和20 Hz的疗效优于5 Hz。     

Efficacy of spinal cord stimulation for neuropathic pain: assessment by abstinence

Assessment of the efficacy of spinal cord stimulation (SCS) against neuropathic pain remains problematic. Some patients may underestimate this, as revealed by their reaction to stimulator malfunction. This study investigated whether abstinence from SCS would provide an indication of its effectiveness. Patients were invited to complete two brief questionnaires each day for 50 days including two periods of 14 days without stimulation. Pain level, sleep quality, activity level and drug intake were recorded. Of 75 patients thought to be using their stimulators, 12 did not respond to the invitation, eight had unresolved technical problems and one no longer needed SCS. Of the 54 remaining, 10 did not wish to be without SCS and 15 declined without giving a reason. Thus 29 agreed to take part but three then dropped out through illness and questionnaires were not received from 10. Ten returned completed questionnaires but failed to follow the protocol; five of these were unable to leave their stimulators off. Only six took part correctly. Twenty of the 29 had received a preliminary explanatory home visit and for nine this was done by telephone. The former produced a considerably higher yield. All six who completed the study correctly had statistically significantly lower pain scores during stimulation. Four had improved sleep but only one reduced his medication and none of the six increased their activity levels. Correlation with previous clinical assessments is discussed. It is concluded that the abstinence principle might provide a useful tool but its power is very methodology-dependent.     

Depression,anxiety, health-related quality of life and pain in patients with chronic fibromyalgia and neuropathic pain

Chronic pain is often associated with comorbidities such as anxiety and depression, resulting in a low health-related quality of life. The mechanisms underlying this association are not clear, but a disturbance in the pain control systems from the brain stem has been suggested. Thirty neuropathic pain (NP) patients, 28 patients with fibromyalgia (FM), and 26 pain-free age- and gender-matched controls were included and examined with respect to mental distress (self-rated Symptom Checklist-92), depression (doctor-rated Hamilton Depression Scale and self-rated Major Depression Inventory), and anxiety (doctor-rated Hamilton Anxiety Scale and self-rated Anxiety Inventory). In addition, patients assessed their health-related quality of life (SF-36). Chronic pain patients with FM and NP had significantly more mental distress including depression and anxiety than healthy controls both by self-rating and by a professional rating. However, these scores are low compared to other studies on mental distress in chronic pain patients. Only few chronic pain patients meet the diagnostic criteria for depression (NP 3.3%, FM 7.1%), and associations between pain and mental symptoms were only found in the FM group despite similar pain intensities. The findings suggest that different mechanisms are responsible for the development of mood disorders in the two patient groups.