Clinical correlates of painful diabetic neuropathy and relationship of neuropathic pain with sensorimotor and autonomic nerve function

Background: This study investigated the clinical correlates of painful diabetic polyneuropathy (PDPN) and the relationship of neuropathic pain with sensorimotor and autonomic nerve function. Methods: Seventy‐eight diabetic patients with PDPN (PDPN⁺), 57 with non‐painful diabetic polyneuropathy (DPN⁺), and 56 without diabetic polyneuropathy (DPN^?) were prospectively studied. Autonomic neuropathy, neuropathic symptoms and signs, vibration perception threshold, and neuropathic pain were assessed using 4 cardiovascular tests, scoring systems for symptoms and signs (Michigan Diabetic Neuropathy Score, MDNS), Biothesiometer, and a numerical rating scale. Results: Compared to DPN⁺, PDPN⁺ patients displayed higher BMI (P =0.0043), waist circumference (P =0.0057), neuropathy symptom score (P <0.0001), MDNS (P <0.0001), and lower Valsalva ratio (P =0.037). In a multiple logistic regression analysis including PDPN as the dependent variable and age, sex, body mass index (BMI), abdominal obesity, diabetes type, diabetes duration, HbA1c, blood pressure, triglycerides, smoking, peripheral arterial disease, Valsalva ratio and MDNS as the independent variables, BMI (OR 1.22, P =0.0012) and MDNS (OR 1.27, P =0.0005) were significantly and independently associated with PDPN. In a multivariate regression analysis including as independent variables also sex, age, diabetes type, diabetes duration and Valsalva ratio, 24‐h pain score was significantly related to neuropathy symptom score (P =0.0011), MDNS (P =0.0158), and 10 g monofilament (P =0.018). Discussion: BMI and sensorimotor deficits were the main determinants of PDPN and, as a novel finding, neuropathic pain intensity was related to the degree of neuropathy deficits. Thus, some peculiarity exists in metabolic correlates of diabetic neuropathic pain compared to insensate neuropathy but painfulness can still coexist with insensitivity.     

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.     

Prevalence of neuropathic pain among patients with chronic low-back pain in the Arabian Gulf Region assessed using the leeds assessment of neuropathic symptoms and signs pain scale

This prospective, multicentre, epidemiological study was designed to assess the prevalence of neuropathic pain among adults with chronic low-back pain (LBP) in the Arabian Gulf region. A total of 1134 patients recruited from the outpatient medical setting were assessed using the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) Pain Scale. A LANSS Pain Scale score ≥ 12 was used to differentiate between patients with a neuropathic contribution to their pain and those with nociceptive pain only. Using this criterion, 628 patients (55%) were classified as having neuropathic pain. Factors associated with neuropathic pain included advanced age, female gender and diabetes with or without hypertension. It was concluded that neuropathic pain is a major contributor to chronic LBP in the Gulf region, and that the LANSS Pain Scale is a practical and rapidly administered screening test for distinguishing the relative contributions of neuropathic and nociceptive pain in patients with chronic LBP that resulted in the use of a more appropriate treatment.     

The Histamine-Induced Axon-Reflex Response in People With Type 1 Diabetes With and Without Peripheral Neuropathy and Pain: A Clinical,Observational Study

Small nerve fibres are important when studying diabetic peripheral neuropathy (DPN) as they could be first affected. However, assessing their integrity and function adequately remains a major challenge. The aim of this study was to investigate the association between different degrees of DPN, the presence of neuropathic pain, and the intensity of the axon-reflex flare response provoked by epidermal histamine. Eighty adults were included and divided into 4 groups of 20 with type 1 diabetes and: painful DPN (T1DM+PDPN), non-painful DPN (T1DM+DPN), no DPN and no pain (T1DM-DPN), and 20 persons without diabetes or pain (HC). The vasomotor responses were captured by a Full-field Laser Speckle Perfusion Imager. The response was lowest in T1DM+DPN, followed by T1DM+PDPN, T1DM-DPN and HC. The response was significantly reduced in DPN (T1DM+DPN, T1DM+PDPN) compared with people without (T1DM-DPN, HC) (P < .001). The response was also attenuated in diabetes irrespective of the degree of DPN (T1DM+PDPN, T1DM+DPN, T1DM-DPN) (P < .001). There were no differences in the response between painful neuropathy (T1DM+PDPN) and painless DPN (T1DM+DPN) (P = .189). The method can distinguish between groups with and without diabetes and with and without DPN but cannot distinguish between groups with and without painful DPN.PerspectiveThis study describes how diabetes attenuates the axon-reflex response, and how it is affected by neuropathy and pain clarifying previous findings. Furthermore, the study is the first to utilize histamine when evoking the response, thus providing a new and fast alternative for future studies into the pathophysiology of neuropathic pain.     

Translation and Linguistic Validation of the Self‐Completed Leeds Assessment of Neuropathic Symptoms and Signs (S‐LANSS) Scale for Use in a Libyan Population

Background: The Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale is used to identify pain of neuropathic origin and has been validated as a self‐completed tool (S‐LANSS). We translated the S‐LANSS into Arabic and evaluated its reliability and linguistic validity for use by Libyan people. Methods: Thirteen of 45 Libyan nationals living in the UK were identified as having chronic pain and completed an English and Arabic S‐LANSS 1 week apart. In addition, 23 of 104 respondents to a telephone interview in Derna City, Libya, were identified as having chronic pain and completed the Arabic S‐LANSS. Seven of these 23 completed the S‐LANSS again 1 week later. Results: Cronbach’s alpha was 0.72 (P < 0.001) for the Arabic S‐LANSS and 0.71 (P < 0.001) for the English S‐LANSS. There was good measurement of agreement of individual items in Arabic and English S‐LANSS tools with kappa coefficients ranging from 0.69 to 1.00. Twelve of the 23 (52.2%) individuals with chronic pain scored 12 or more on the Arabic S‐LANSS and were classified as possibly having neuropathic pain. There was good measurement of agreement of individual items in Arabic S‐LANSS tools with kappa coefficients ranging from 0.462 to 1.00. There were strong intraclass correlations in both versions for test‐retest reliability of total score. Conclusion: The Arabic S‐LANSS is reliable and linguistically valid to use in Libya. Perspective: Our translation of the S‐LANSS into Arabic was shown to be linguistically valid and reliable for use in a Libyan population.     

3种神经病理性疼痛筛查量表在中轴型脊柱关节炎患者中的评价

目的 比较3种神经病理性疼痛筛查量表在中轴型脊柱关节炎患者中的信度、效度和适用性。方法 采用painDETECT问卷、神经病理性疼痛4问卷和利兹神经病理性症状和体征评估疼痛量表对186例中轴型脊柱关节炎患者进行调查,评价量表的信度和效度。结果 painDETECT问卷、神经病理性疼痛4问卷和利兹神经病理性症状和体征评估疼痛量表的Cronbach α系数分别为0.807,0.697和0.623, Guttman分半系数分别为0.846、0.691和0.701。painDETECT问卷共提取2个公因子,累计方差贡献率55.171%。神经病理性疼痛4问卷共提取4个公因子,累计方差贡献率66.627%。利兹神经病理性症状和体征评估疼痛量表共提取2个公因子,累计方差贡献率50.836%。3种量表评估结果一致性Kappa值和相关性r值均大于0.500。患者对3种量表首选率分别为71.5%、3.2%和14.0%。结论 painDETECT问卷信度和效度良好,首选率最高。其余2种量表信度尚可,效度良好。3种量表一致性与相关性较强。     

A Comparison of the DN4 and LANSS Questionnaires in the Assessment of Neuropathic Pain: Validity and Reliability of the Turkish Version of DN4

A screening tool that quickly and correctly differentiates neuropathic pain from non-neuropathic pain is essential. Although there are many screening tools in the assessment of neuropathic pain, many physicians still have the problem of not being able to identify their neuropathic pain patients easily. In this study, we assessed the test-retest reliability, internal consistency, and validity of the Turkish version of DN4 questionnaire. Within the same group of patients, we also compared the DN4 with the LANSS questionnaire. A total of 180 patients (n = 121 with neuropathic pain and n = 59 with non-neuropathic pain characteristics) were enrolled. In our study population, peripheral origin of neuropathic pain, mainly radiculopathies and polyneuropathies, dominated. The reliability and validity of Turkish version of DN4 were found to be high. The sensitivities of the DN4 and the LANSS were 95% and 70.2%, respectively. The specificity of both tests was 96.6%. The strengths and weaknesses of these questionnaires are discussed.     

Capsaicin 8% Dermal Patch for Neuropathic Pain in a Pain Unit

AimsPain units manage approximately 20% of the patients with neuropathic pain, usually presenting with severe uncontrolled pain associated with substantial impairment of quality-of-life and disability. We aimed to analyze the experience with the capsaicin 8% dermal patch for managing patients with neuropathic pain in a pain unit.DesignThis was a post-authorization observational and retrospective study conducted at a single pain unit on patients with peripheral neuropathic pain under routine clinical care.MethodsDiagnosis of neuropathic pain was based on the Douleur Neuropathique 4 (DN4) questionnaire. Evaluations included pain intensity according to a visual analog scale and the quality-of-life as evaluated with the European Quality of Life-5 Dimensions (EQ-5D).ResultsWe included 66 patients with neuropathic pain lasting for a median of 24 months. The most frequent diagnosis was iatrogenic neuropathic pain (47%) and two thirds of patients exhibited extreme pain or discomfort. Pain intensity was reduced significantly from a mean (standard deviation [SD]) of 7.20 (1.95) at baseline to 6.02 (2.77) at month 3, leading to a mean change from baseline of 1.19 (95% confidence interval [CI], 0.59 to 1.78; p < .001; Cohen's d 0.49). The extent of the pain area was also significantly reduced from a median (interquartile range [IQR]) of 169.5 cm² (69.3-299.9) at baseline to 121.2 cm² (35.4-183.9) at month 3 (p < .001). There was an improvement in most dimensions of quality-of-life, especially regarding “usual activities,” “pain/discomfort,” and “anxiety/depression.” Tolerability was consistent with the known profile.ConclusionsOur results suggest that the capsaicin 8% dermal patch is a useful and well-tolerated treatment option for managing peripheral neuropathic pain in pain units.     

Classifying post‐stroke shoulder pain: Can the DN4 be helpful?

The etiology of post‐stroke shoulder pain (PSSP) is largely unclear and may involve both nociceptive and neuropathic mechanisms. No gold standard is present for PSSP diagnosis. The neuropathic pain diagnostic questionnaire (DN4), was originally developed to identify neuropathic pain in the clinical context. In this study we used the DN4 to categorize PSSP patients and compared symptoms and signs suggestive of either nociceptive or neuropathic pain. Pain complaints and sensory functions were compared between patients with chronic PSSP scoring at least four (DN4+, n=9) or less than four (DN4⁻, n=10) on the DN4. Pain was assessed using a numeric rating scale and the McGill pain questionnaire. Sensory functions were assessed using clinical examination and quantitative sensory testing combined with a cold pressor test. Patients classified as DN4+ reported constant pain, higher pain intensity, a higher impact of pain on daily living, more frequent loss of cold sensation, reduced QST thresholds at the unaffected side and increased QST thresholds at the affected side. Notably, several symptoms and signs suggestive of either neuropathic or nociceptive pain corresponded to the subgroups DN4+ and DN4⁻ respectively. However, since the pathophysiological mechanisms remain unclear and none of the sensory signs could be exclusively related to either DN4+ or DN4⁻, PSSP prognosis and treatment should not be solely based on the DN4. Nonetheless, a thorough assessment of neuropathic and nociceptive pain complaints and somatosensory functions should be included in the diagnostic work‐up of PSSP.     

Translation to Portuguese and Validation of the Douleur Neuropathique 4 Questionnaire

The Douleur Neuropathique 4 (DN4) questionnaire was developed by the French Neuropathic Pain Group and is a simple and objective tool, with the ability to distinguish nociceptive from neuropathic pain. The purpose of this work was to validate the DN4 questionnaire in the Portuguese language in order to allow its use in clinical and research settings. A double-blind, accuracy study was conducted, consisting of translation, back-translation, literal evaluation, semantic equivalence, and communication with the target population. The Portuguese version of the questionnaire was applied in a sample of 101 patients with neuropathic (N = 42) or nociceptive pain (N = 59), ranked according to medical diagnosis. The reproducibility, reliability and validity of the instrument were analyzed, and showed a high diagnostic power for this version of the DN4 questionnaire. The Portuguese version of the DN4 questionnaire presented good validity and reliability, allowing it to identify neuropathic pain and neuropathic characteristics of mixed pain syndromes.PerspectiveThis article presents the first validated neuropathic pain questionnaire in the Portuguese language and represents a useful tool in the assessment of neuropathic pain both in the clinical setting and in population-based studies. The sensible and quick format of this instrument are key factors that will contribute to its widespread use, permitting a true recognition of patients with neuropathic pain.     

Gait stability of diabetic patients is altered with the rigid rocker shoes

BackgroundRigid-rocker shoes may induce gait instability in diabetics, however, this is not clearly investigated. The present study investigates if rigid-rocker shoes influence diabetic gait stability.MethodsFourteen non-neuropathic and nine neuropathic diabetics, plus eleven healthy young-adults were recruited. Full-body kinematic data was captured during walking. Experimental conditions included barefoot and three rocker-shoe designs according to the rocker angle, apex angle and apex position (R10: 10°, 80°, 60%; R15: 15°, 95°, 52%; R20: 20°, 95°, 60%). Sagittal and frontal stability margin, plus fear of fall were main outcome measures.Findings.Sagittal stability margin was not affected by health, however, was increased with R10 and R15 in non-neuropathic diabetics and healthy individuals (R² = 0.16). Variability of sagittal stability margin was not altered in neuropathic diabetics, but was increased with R15 and R20 in healthy participants, with R15 in non-neuropathic diabetics (R² = 0.12). Frontal stability margin (R² = 0.46) and its variability (R² = 0.39) were significantly increased in neuropathic and non-neuropathic diabetics compared to healthy individuals. Frontal stability margin was significantly higher with R15 in neuropathic diabetics, and with R20 in both non-neuropathic and healthy participants. Sagittal and frontal stability margin were strongly correlated with fear of fall in neuropathic diabetics.Interpretations.R15 and R20 might challenge gait stability of diabetics cause them restrict centre of mass motion thereby imposing a tighter control over walking. However, neuropathic diabetics generally walk very cautious due to neuropathy and increased fear of fall. Frontal stability margin, highly affected by health and experimental condition, is a more sensitive indicator of gait stability.     

Can the LANSS scale be used to classify pain in chronic cancer pain trials?

Purpose

The Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scale was developed to differentiate pain of predominantly neuropathic or nociceptive origin. The aim of this study was to determine whether the LANSS scale was an appropriate tool to classify pain in a trial of patients with advanced cancer and chronic refractory pain.

Methods

Clinician assessment of pain type (neuropathic or nociceptive) was used to determine the sensitivity and specificity of LANSS scores in 112 trial participants. Those classified as "mixed" or of uncertain aetiology were excluded. We undertook several analyses in an attempt to improve the LANSS scale and better diagnose pain type for our specific dataset.

Results

There was strong association between the LANSS score and a diagnosis of neuropathic versus nociceptive pain, p?<?0.001. When the clinical assessment was compared with the LANSS scale, the overall accuracy was 94 % (79/84). The 5 false negatives and no false positives resulted in a sensitivity of 0.86 (0.70, 0.95), specificity of 1 (0.93, 1), positive predictive value of 1 (0.88, 1) and negative predictive value of 0.91 (0.80, 0.97). The negative likelihood ratio was 0.14 (0, 0.32). The scale had good discriminant and construct validity. Reliability was assessed via internal consistency with Cronbach's α?=?0.76, similar to that of the original validation study (α?=?0.74). None of the new scales developed was better at differentiating pain type.

Conclusions

The LANSS scale predicted well for pain type in a cancer population and is a useful tool for classifying pain in cancer pain trials.     

The specific disease burden of neuropathic pain: results of a French nationwide survey

We report the first nationwide survey of the impact of neuropathic pain, as opposed to nonneuropathic pain, on quality of life and health care utilization in the French general population. A postal questionnaire was sent to a representative sample of 4554 respondents from an initial nationwide survey of 30,155 subjects with or without chronic pain. It included pain characteristics (Neuropathic Pain Symptom Inventory, DN4), quality of life (Medical Outcomes Short Form 12, SF-12), sleep, anxiety/depressive symptoms (Hospital Anxiety and Depression Scale) and health care utilization. In total, 3899 (85.6%) questionnaires were returned, 3816 (97.9%) could be assessed and 3165 subjects (82.9%) confirmed their pain status. Subjects reporting pain and neuropathic characteristics based on the DN4 displayed a higher degree of impairment of all dimensions relating to quality of life and sleep and had higher anxiety/depression scores than those reporting pain without neuropathic characteristics and those without pain (P < .01). They also made greater use of health care facilities, particularly as concerned neurological treatments and visits to neurologists (21% vs 9%; P < .01). Multivariate analyses showed that the neuropathic characteristics of pain made an independent contribution to quality-of-life impairment (P < .0001 and P = .0005 for the physical and mental scores of the SF-12 respectively). Our study indicates that the disease burden of chronic pain depends on the nature of the pain, independently of its intensity and duration.     

An evaluation of quality of life,physical activity level and symptoms in patients with early stages of chronic venous disease

BackgroundChronic venous disease (CVD) is a common, long-term disease that has a variety of symptoms, signs and decreases the patients’ quality of life (QoL) of the patients. The aim of this study was to evaluate QoL, symptoms, and physical activity level of CVD patients with early stages (C₁ and C₂ classes).MethodsThe sample of this study composed of 40 patients diagnosed with CVD. The data were collected by face-to-face interview method in the cardiovascular surgery outpatient clinic. Participants were diagnosed with duplex ultrasound (DUS). A personal information form, venous insufficiency epidemiological and economic study-quality of life/symptoms (VEINS-QOL/Sym), and international physical activity questionnaire were used to assess the participants.ResultsAccording to DUS results, 23 participants had unilateral CVD, 17 participants had bilateral CVD. Thirty-six of these limbs were stage C₂ according to CEAP, twenty one were stage C_3. The patients with CVD had low QoL and physical activity level, also moderate pain intensity. Pain, swelling, restless leg, heavy legs, night cramps, and itching were more common symptoms. There was no statistical difference between unilateral/bilateral CVD patients in QoL scores, physical activity level, and pain intensity (p˃0.05).ConclusionThere was no difference between the extent and severity of the disease and QoL, physical activity level, variety of symptoms. To increase the physical activity level and to evaluate the quality of life may be important for the management of the disease from the early stages of the disease (C₁ and C₂ classes).     

Validation of a New Arabic Version of the Neuropathic Pain Diagnostic Questionnaire (DN4)

The “Douleur Neuropathique 4 (DN4) questionnaire” was developed for screening neuropathic pain. The purpose of this work was to validate the DN4 questionnaire in the standard Arabic language. First, the questionnaire was translated and semantically adapted to Arabic according to the international guidelines for cross‐cultural adaptation. Second, a prospective observational study was performed to validate this questionnaire. A total of 195 patients with chronic pain (n = 99 with neuropathic pain and n = 96 without neuropathic pain) were enrolled in the study. The internal consistency Kuder–Richardson's Formula 20 for the whole DN4 questionnaire was 0.86 (P < 0.001) and the intraclass correlation coefficient 0.99 (95% CI: 0.99 to 1.00). The test–retest reliability kappa coefficient for each item ranged from 0.92 to 1.00. Using a receiver‐operating characteristic (ROC) curve analysis, the areas under the curve were 0.94 and 0.97 for the 7‐item DN4 and 10‐item DN4, respectively. A cut‐off score of 3 resulted in a sensitivity of 97.0% and a specificity of 82.3% for the 7‐item DN4, while a cut‐off score of 5 for the 10‐item DN4 resulted in a sensitivity of 93.0% and a specificity of 95.8%. Tingling, numbness, and hypoesthesia to touch and to pricking were the most discriminating pain items. The sensitivity and specificity of the 7‐item DN4 and 10‐item DN4 were not influenced by either pain severity or educational level. In conclusion, this new Arabic version DN4 questionnaire is a simple, reliable, and valid tool for discriminating between neuropathic and non‐neuropathic pain. It represents a useful tool in clinical setting and population‐based studies.