Evaluation Of Neuropathic Pain Assessment Tools In Patients With Painful Diabetic Peripheral Neuropathy

BackgroundDiabetes is the most common chronic disease, with diabetic peripheral neuropathy (DPN) one of the common complications. Symptoms of DPN may include numbness, burning, pins and needles, sometimes with allodynia. Painful diabetic peripheral neuropathy (PDPN) is caused by abnormalities of the peripheral nervous system in patients with diabetes. Prevalence of PDPN varies, from 14.4% to 65.3%. PDPN seriously affects the quality of life of patients, with pain severity associated with anxiety and depression. Patients with PDPN have significantly greater healthcare resource utilization and costs than patients with diabetes only, with the highest burden associated with severe PDPN. Early detection of the presence of PDPN contributes to the treatment outcome. Effective pain assessment tools are helpful for the diagnosis of PDPN.However, the diagnosis of PDPN is difficult, no clear diagnostic criteria exist for PDPN in clinical practice. There are many neuropathic pain assessment tools, including the most widely used Leeds Assessment of Neuropathic Symptoms and Signs (LANSS), Douleur Neuropathique 4 questionnaire (DN4), Brief Pain Inventory for Diabetic Peripheral Neuropathy (BPI-DPN), Neuropathic Pain Questionnaire (NPQ), Neuropathic Pain Scale (NPS), and Short-form McGill Pain Questionnaire-2 (SF-MPQ-2). The LANSS was developed by Bennett in 2001 and has been translated into Portuguese, Spanish, Turkish and other languages. The Chinese version of the LANSS was translated and validated by Li et al. in 2011 and proved to have good reliability and validity. The DN4 was designed by a French pain expert group in 2005 and has been translated into Arabic, Dutch, Greek and several other languages, except there has been no report on a Chinese version. The LANSS and the DN4 have been used to distinguish neuropathic pain from nonneuropathic pain, but not for patients with PDPN specifically. The Brief Pain Inventory (BPI) was developed by Cleeland & Ryan in 1994 and the Chinese version of the BPI has been widely used to assess acute pain, chronic pain and cancer pain. The BPI-DPN was revised by Zelman et al. in 2005, to assess Chinese PDPN patients, but no reports were noted in China.ObjectivesThe objectives of this study were to evaluate the reliability and validity of the LANSS, the DN4 and the BPI-DPN in Chinese patients with PDPN, and to compare the diagnositic sensitivity of the LANSS and the DN4, to provide effective assessment tools for Chinese patients with PDPN.Methods1. SubjectsA convenience sample was recruited at inpatient and outpatient departments of endocrinology, inpatient department of pain, and outpatient department of orthopedics from five Level Three general hospitals in Guangzhou from May 2014 to January 2015. Inclusion criteria were age≥18; complaint of pain; had one of the following diagnosis:neuropathic pain (PDPN), or nonneuropathic pain (low back pain, myofascial pain syndrome, ankylosing spondylitis, shoulder arthritis, headache, osteoporosis, carpal tunnel syndrome, rib cartilage inflammation, or osteoarthritis, etc.), and willing and able to complete the questionnaire. Exclusion criteria were patients with neuropathic pain due to other causes or with mixed pain; with a history of foot ulcers or severe comorbidities, or lower limb amputation; inability to communicate and complete questionnaire. Instruments2. Instruments2.1 Leeds Assessment of Neuropathic Symptoms and Signs (LANSS)The LANSS was developed to distinguish neuropathic pain from nociceptive pain. It consists of pain questionnaire and sensory testing with seven items with overall score of 24. Pain questionnaire includes sensations like pricking, tingling, pins and needles, skin discoloration, light touch pain, sensations like electric shocks, jumping and bursting, and feeling of altered skin temperature like hot and burning. Sensory testing includes allodynia and altered pin-prick threshold. If the pain symptom is consistent with the description, subjects answer’yes’, scoring items 5,5, 3,2,1,5 and 3, respectively, and inconsistent answer is "no",0 point. If the overall score> 12, neuropathic mechanisms are likely to be contribution to the patient’s pain. The Chinese version of the LANSS translated by Li et al. was used in this study.2.2 Douleur Neuropathique 4 questionnaire (DN4)The DN4 consists of four questionnaires in two parts, i.e., interview of the patients and examination of the patient, with a total of 10 items. The items are burning, painful cold, electric shocks, tingling, pins and needles, numbness, itching, hypoesthesia to touch, hypoesthesia to prick, and brushing. Each item is scored "yes" and "no". Each "yes" item is scored 1 and "no" 0, with a total score possible of 10. The total score≥ 4 indicates neuropathic pain. The Chinese version of the DN4 was translated by two nursing master candidates and back-translated by a pain care specialist.2.3 Brief Pain Inventory for Diabetic Peripheral Neuropathy (BPI-DPN)The Brief Pain Inventory (BPI) includes pain intensity and pain interference on a 0-10 numeric rating scale. The pain intensity includes worst pain, least pain, average pain in the last 24 hours, and current pain. The pain interference includes general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life during the past 24 hours. The BPI-DPN is a revision of the BPI, to phrase all items with "due to diabetes". It is used to assess the pain intensity and pain interference of patients with PDPN in this study.3. Study ProceduresHuman subject ethic review was approved by the institutional review board and informed consent to participate was obtained before data collection. Two master students and one registered nurse were trained as investigators to conduct the assessments. Same person do all the data collection and all the tools were completed at one time in the same order (LANSS, DN4, BPI-DPN).Demographic characteristics (gender, age and education), diagnosis (diabetes, pain related diseases and other chronic diseases), life styles and self management (smoking and drinking), and physical examination results including height, weight and blood pressure were collected. For patients with PDPN, duration of diabetes, family history of diabetes, history of hypertension, the most recent laboratory test results (blood glucose and blood lipids) and clinical treatment regimen were also collected.4. Statistical AnalysesAnalyses were performed using SPSS 13.0. Quantitative variables were described using mean ± SD, and percentage for categorical variables. Comparisons between quantitative data used independent samples t test and categorical data was carried out using Chi-square test. Reliability was evaluated by internal consistency of Cronbach’s a coefficient and Guttman split-half. Construct validity was analyzed by factor analysis and Spearman correlation coefficients. Receiver operating characteristic curve (ROC) area under the curve (AUC), sensitivity and specificity were also analyzed.Results1. Demographic and clinical characteristicsA total of one hundred and seventy patients were recruited in the study. Seventy patients were male (41.2%) and 100 female (58.8%), age ranged from 23 to 90 years with mean age 59.67 ±12.77 years. The number of patients with PDPN were 100 (58.8%), and 70 (41.2%) had nonneuropathic pain. In nonneuropathic pain patients, the painful diagnoses included osteoarthritis 36 (51.4%), low back pain 16 (22.9%), shoulder arthritis 5 (7.1%), myofascial pain syndrome 5 (7.1%), rib cartilage inflammation 2 (2.9%), carpal syndrome 2 (2.9%), headache 2 (2.9%), ankylosing spondylitis 1 (1.4%), and osteoporosis 1 (1.4%).2. ReliabilityIn PDPN patients, the Cronbach’s a coefficient of the LANSS was 0.735, Guttman split-half coefficient 0.660. The Cronbach’s a coefficient of the DN4 was 0.750, Guttman split-half coefficient 0.726. The Cronbach’s a coefficient of the BPI-DPN was 0.898, Guttman split-half coefficient 0.849.3. ValidityThe principal component analysis of the LANSS showed that the factor/ principal component of eigenvalue greater than one was two and variance contribution rate was 42.956% and 18.989%, respectively, and the total cumulative variance contribution rate was 61.945%. Using orthogonal rotation transformation and original items corresponding to the maximum load factor, the original variable was divided into two dimensions, consistent with the original scale structure. The correlation coefficient between each item score and total score were higher than 0.400, except the item correlation coefficient between skin temperature and total score was 0.383. Sensitivity and specificity were 58.0%,97.1%, respectively. The AUC was 0.976.The principal component analysis of the DN4 scale conveyed that the factor/ principal component of eigenvalue greater than one was three and variance contribution rate was 32.618%,12.605%and 11.787%, respectively, and the total cumulative variance contribution rate was 57.010%. Using rotation transformation, the original variable was divided into four dimensions, consistent with the original scale structure. The correlation coefficient between each item score and total score were higher than 0.300, except for the item painful cold. Sensitivity and specificity were 82.7%,97.1%, respectively. The AUC was 0.971.The principal component analysis of the BPI-DPN conveyed that the factor/ principal component of eigenvalue greater than one was two and variance contribution rate was 50.646% and 15.411%, respectively, and the total cumulative variance contribution rate was 66.056%. Using rotation transformation, the original variable was divided into two dimensions, consistent with the original scale structure, high discriminant validity.4. Pain severity and pain interference in patients with PDPNFor pain intensity, the mean score of worst pain was 7.18 ± 1.70, least pain 4.05 ±2.34, average pain 5.70 ±1.76, and current pain 5.06 ± 2.35. For pain interference, the mean score for general activity was 6.57±2.67, mood 6.05 ±2.53, walking ability 6.62±2.79, normal work 6.88±3.05, relations with other people 5.03±2.54, sleep 7.29±2.15, and enjoyment of life 6.40±2.78. The majority level of worst pain, least pain, average pain in the past 24 hours and current pain were above the medium level, and the pain interference for patients increased with pain intensity.ConclusionsThe LANSS, the DN4 and the BPI-DPN have good reliability and validity when used to assess pain in Chinese patients with PDPN. Compared to the LANSS, the DN4 has higher diagnostic sensitivity. These three tools could be clinically used for pain assessment of Chinese patients with PDPN. Besides, pain in patients with PDPN was poorly managed and pain relief needs to be improved.