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.     

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.     

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.     

Identifying neuropathic back and leg pain: a cross-sectional study

Low back pain is a widespread debilitating problem with a lifetime prevalence of 80%, with the underlying pain mechanism unknown in approximately 90% of cases. We used the painDETECT neuropathic pain screening questionnaire to identify likely pain mechanisms in 343 patients with low back pain with or without leg pain in southeastern England referred for physiotherapy. We related the identified possible pain mechanisms nociceptive, unclear, and neuropathic to standardised measures of pain severity (Numeric Rating Scale), disability (Roland Morris Low Back Pain Disability Questionnaire), anxiety and depression (Hospital Anxiety and Depression Scale), and quality of life (Short Form 36 Health Survey Questionnaire Version 2). In addition, we investigated any relationship between these possible pain mechanisms and leg pain, passive straight leg raise, and magnetic resonance imaging evidence confirming or eliminating nerve root compression. A total of 59% of participants (n = 204) reported likely nociceptive pain, 25% (n = 85) unclear, and 16% (n = 54) possible neuropathic pain. The possible neuropathic pain group reported significantly higher pain, disability, anxiety, and depression, reduced quality of life and passive straight leg raise compared to the other pain groups (P < .05). A total of 96% of participants with possible neuropathic pain reported pain radiating to the leg (76% below the knee); however, leg pain was still more common in patients with nociceptive pain, suggesting that leg pain is sensitive to, but not specific to, possible neuropathic pain. No relationship was demonstrated between possible neuropathic pain and evidence for or absence of nerve root compression on magnetic resonance imaging scans. These findings suggest possible neuropathic pain is less common in low back pain patients referred through primary care and clarifies the usefulness of clinical tests for identifying possible neuropathic pain.     

A prospective study of neuropathic pain induced by thoracotomy: incidence, clinical description, and diagnosis

This study evaluated prospectively the incidence of neuropathic pain after thoracotomy, described its clinical characteristics, and delineated landmarks for its diagnosis in daily practice. We evaluated clinically painful symptoms and sensory deficits in 54 patients after lateral/posterolateral thoracotomy for broncho-pulmonary carcinoma with standardized surgical and analgesic procedures. At 2 months, 49 patients suffered from non malignant thoracic pain, and at 6 months 38 patients (loss to follow-up for 7) reported persisting pain. In 35 patients, painful symptoms and sensory deficits could be evaluated using a standardized clinical bedside procedure. According to the grading system proposed by Treede et al. [41], neuropathic pain was considered probable in 21 patients, while use of the DN4 questionnaire concluded that neuropathic pain was probable in 17 patients. The two diagnostic procedures provided similar conclusions in 16 patients. Morphine consumption during the early post-operative period (mean 111.3 ± 30.8 mg/day) and pain intensity (VAS: mean 5.71 ± 2.1) were significantly higher in patients suffering from neuropathic pain than in other patients with pain (mean 80 ± 21.4 mg/day; VAS: mean 3.9 ± 2.4). The clinical picture in most patients with neuropathic pain included electric shocks and severe multimodal hypoesthesia in the sensory area of 5th/6th intercostal nerves. Thus, our results indicate a minimal incidence of chronic post-thoracotomy pain at 70% and that of neuropathic pain at 29%, this latter being clinically suggested by a combination of certain symptoms and reinforced by the DN4 questionnaire when sensory deficit at scar is present.     

Pregabalin for peripheral neuropathic pain: results of a multicenter, non-comparative, open-label study in Indian patients

The aim of this study was to evaluate the tolerability, safety and efficacy of pregabalin in Indian patients with peripheral neuropathic pain. In this prospective, multicenter, non-comparative, open-label study, patients with peripheral neuropathic pain (n = 111) received pregabalin in doses ranging from 75 to 300 mg twice daily for 3 weeks. Primary efficacy measures included weekly pain score and the Visual Analogue Scale (VAS) score of the Short-Form McGill Pain Questionnaire (SF-MPQ). Despite a short study duration, a significant reduction was seen in weekly pain score (p < 0.0001), as well as VAS score of SF-MPQ (p < 0.0001). Significant improvements were also seen in other pain-related endpoints, weekly sleep interference score, quality of life measures, and patient and clinician ratings of global improvement. Pregabalin was well tolerated, and the most common adverse events were dizziness and somnolence. The short study duration precluded the assessment of longer term safety issues such as weight gain. This study has demonstrated the safety, tolerability and efficacy of pregabalin for peripheral neuropathic pain in Indian patients.     

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。     

Dysynchiria is not a common feature of neuropathic pain

Patients with chronic neuropathic pain (non‐CRPS) and brush‐evoked allodynia watched a reflected image of their corresponding but opposite skin region being brushed in a mirror. Unlike complex regional pain syndrome Type 1, this process did not evoke any sensation at the affected area (‘dysynchiria’). We conclude that central nociceptive sensitisation alone is not sufficient to cause dysynchiria in neuropathic pain. The results imply a difference in cortical pain processing between complex regional pain syndrome and other chronic neuropathic pain.     

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。     

Risk factors predictive of chronic postsurgical neuropathic pain: the value of the iliac crest bone harvest model

Nerve lesions and secondary hyperalgesia may both be present after surgery, and their relative contributions to chronic postsurgical neuropathic pain (CPSNP) remain unclear. This prospective study explored the roles of these factors in the development of CPSNP after iliac crest bone harvest. CPSNP was defined as pain in the area of hypoesthesia, with a positive Douleur neuropathique 4 questionnaire (DN4) score 3 months after iliac crest bone harvest. The location, intensity, and neuropathic characteristics of pain were evaluated in 82 patients who were followed for 6 months. Neuropathic characteristics were assessed by clinical examination and DN4 questionnaire. The area of secondary hyperalgesia was evaluated 48 h and 1 month after surgery. The area of mechanical hypoesthesia, detection, and mechanical pain threshold were evaluated at 48 h and at 1 and 3 months. Nineteen patients (23%) had CPSNP at 3 months. The patients who developed CPSNP had a larger area of secondary hyperalgesia at 48 h (88 cm(2) vs 33 cm(2); P=.001), higher pain intensity (numerical rating scale 6.7 vs 4.7; P=.02), and higher neuropathic characteristics score on the DN4 questionnaire (4.3 vs 2.3; P=.001). However, neither the area nor the severity of hypoesthesia differed significantly between patients with and without CPSNP. Two independent, additive predictors of CPSNP were identified: area of secondary hyperalgesia (odds ratio 1.02; P=.004) and DN4 score (odds ratio 1.94; P=.001). These findings suggest that both nerve lesions and central sensitization are involved in CPSNP development and could be seen as early warning signs.     

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.     

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。     

趋化因子CXCL10作为神经病理性疼痛生物标记物的研究

目的:目前临床上缺乏神经病理性疼痛诊断和预后判断的客观指标,本研究旨在检测神经病理性疼痛小鼠和人的脑脊液(cerebrospinal fluid,CSF)和血清中趋化因子CXCL10的表达情况。方法:结扎ICR小鼠L5脊神经(spinal nerve ligation,SNL)构建神经病理性疼痛(neuropathic pain,NP)模型,足底注射福尔马林或完全弗氏佐剂(complete Freund's adjuvant,CFA)建立炎症性疼痛模型;收集捐献者的脑脊液和血液,采用Real-time PCR、半定量PCR、Western Blot、免疫荧光和ELISA方法,分别检测CXCL10和CXCR3的mRNA和蛋白表达、CSF和血清中CXCL10的表达。结果:①Cxcl10在正常ICR小鼠的脾脏、淋巴结、背根神经节(dorsal root ganglion,DRG)、脊髓和脑中有不同程度的基础表达;②Cxcr3在正常ICR小鼠的脾脏、淋巴结、DRG、脊髓和脑中也有不同程度的基础表达;③与假手术组相比,SNL模型小鼠CSF与血清中CXCL10含量显著增加(P<0.05,P<0.01);急性炎症性疼痛小鼠CSF和血清中CXCL10与对照组相比无显著变化;慢性炎症性疼痛小鼠CSF中CXCL10与对照组相比无显著变化;血清中CXCL10显著增加(P<0.05);④健康人类受试者的脊髓、DRG和淋巴结中有CXCL10和CXCR3表达;⑤疱疹后神经痛病人CSF与血清中CXCL10与对照组相比显著增加(P<0.05),骨性关节炎病人CSF和血清中CXCL10无显著增加。结论:神经病理性小鼠CSF和血清以及疱疹后神经痛病人CSF和血清中CXCL10表达显著增加,CXCL10可能作为神经病理性疼痛的生物标志物。     

What is new in neuropathic pain?

Introduction Neuropathic pain occurs in 1% of the population and is difficult to manage. Responses to single drugs are limited in benefit. Thirty percent will fail to respond altogether. This is a review of newer drugs and treatment paradigms. Methods A literature review was performed pertinent to new drugs and treatment algorithms in the management of neuropathic pain. Results New information on opioids (tramadol and buprenorphine) suggests benefits in the management of neuropathic pain and has increased interest in their use earlier in the course of illness. Newer antidepressants, selective noradrenaline, and serotonin reuptake inhibitors (SNRIs) have evidence for benefit and reduced toxicity without an economic disadvantage compared to tricyclic antidepressants (TCAs). Pregabalin and gabapentin are effective in diabetic neuropathy and postherpetic neuralgia. Treatment paradigms are shifting from sequential single drug trials to multiple drug therapies. Evidence is needed to justify this change in treatment approach. Conclusion Drug choices are now based not only on efficacy but also toxicity and drug interactions. For this reason, SNRIs and gabapentin/pregabalin have become popular though efficacy is not better than TCAs. Multiple drug therapies becoming an emergent treatment paradigm research in multiple drug therapy are needed.     

Comparison of psychological and physical function in neuropathic pain and nociceptive pain: Implications for cognitive behavioral pain management programs

Research has increased our understanding of the psychological and physical functioning associated with persistent pain and has facilitated the development of cognitive behavioral pain management programs to help improve people’s physical function and decrease their distress in the presence of persistent pain. The majority of this research has focused on nociceptive pain or pain of mixed etiology. There has been less focus on these aspects of neuropathic pain. It is possible that differences exist in the function and difficulties associated with nociceptive and neuropathic pain. These differences may be associated with our clinical observation that some people with neuropathic pain have difficulty applying some aspects of the theory and practice of cognitive behavioral pain management. The purpose of this study was to compare a single neuropathic pain condition (post-herpetic neuralgia) with a persistent pain of nociceptive origin (low back pain) and determine whether differences exist in: (1) physical and psychological function; (2) factors that increase difficulties; (3) responses to pain; (4) beliefs about pain and (5) problems experienced. The results suggest that the differences between the two groups were not on the major variables of pain, mood, cognition and physical function. The main differences were in factors that increase pain, people’s responses to pain, their beliefs about diagnosis and the cause of pain and the problems they reported as a result of experiencing pain. The implications of our findings for the development of cognitive behavioral pain management programs for people with neuropathic pain are discussed.     

Identification of neuropathic pain in patients with neck/upper limb pain: Application of a grading system and screening tools

The Neuropathic Pain Special Interest Group (NeuPSIG) of the International Association for the Study of Pain has proposed a grading system for the presence of neuropathic pain (NeP) using the following categories: no NeP, possible, probable, or definite NeP. To further evaluate this system, we investigated patients with neck/upper limb pain with a suspected nerve lesion, to explore: (i) the clinical application of this grading system; (ii) the suitability of 2 NeP questionnaires (Leeds Assessment of Neuropathic Symptoms and Signs pain scale [LANSS] and the painDETECT questionnaire [PD-Q]) in identifying NeP in this patient cohort; and (iii) the level of agreement in identifying NeP between the NeuPSIG classification system and 2 NeP questionnaires. Patients (n = 152; age 52 ± 12 years; 53% male) completed the PD-Q and LANSS questionnaire and underwent a comprehensive clinical examination. The NeuPSIG grading system proved feasible for application in this patient cohort, although it required considerable time and expertise. Both questionnaires failed to identify a large number of patients with clinically classified definite NeP (LANSS sensitivity 22%, specificity 88%; PD-Q sensitivity 64%, specificity 62%). These lowered sensitivity scores contrast with those from the original PD-Q and LANSS validation studies and may reflect differences in the clinical characteristics of the study populations. The diagnostic accuracy of LANSS and PD-Q for the identification of NeP in patients with neck/upper limb pain appears limited.