Nepalese version of Douleur Neuropathique 4 (DN4) questionnaire for detection of neuropathic pain signs and symptoms: Translation and psychometric properties.

OBJECTIVE: This study aimed to translate the DN4 questionnaire into Nepalese version and assess its psychometric properties: diagnostic accuracy, internal consistency, and test-retest reliability. METHODS: An observational study was conducted in a tertiary level teaching hospital of Kathmandu, Nepal. We included 166 patients with chronic pain visiting a pain clinic over a period of one year. The Nepalese version of the DN4 questionnaire was used for detecting signs and symptoms of neuropathic pain. The English version of the questionnaire was translated into Nepali in accordance with the standard guideline with the help of linguistic experts. The patients who met the inclusion criteria were examined and interviewed twice in an interval of two weeks. The association between the index test and the reference test was analyzed using Chi-square test. Diagnostic accuracy was assessed using sensitivity, specificity, Youden's index, and positive and negative predictive values. We calculated internal consistency using Cronbach's alpha (∝), and test-retest reliability using Cohen's kappa and Intra-class correlation coefficient (ICC). RESULTS: The study showed a significant association between the result of DN4 questionnaire and the gold standard (physician's diagnosis) (p<0.001). The sensitivity and specificity values for the DN4 questionnaire were 75% and 95.3% respectively. Similarly, positive and negative predictive values were 93.8% and 80.4% respectively. Our study showed adequate internal consistency (∝ = 0.710) and a good test-retest reliability (kappa = 0.872, ICC = 0.877). CONCLUSIONS: The Nepalese version of DN4 questionnaire is a valid and reliable tool for the identification of signs and symptoms of neuropathic pain. This can be used for screening neuropathic pain signs and symptoms in clinical as well as research settings.

Cell migration towards CXCL12 in leukemic cells compared to breast cancer cells.

Chemotaxis or directed cell migration is mediated by signalling events initiated by binding of chemokines to their cognate receptors and the activation of a complex signalling cascade. The molecular signalling pathways involved in cell migration are important to understand cancer cell metastasis. Therefore, we investigated the molecular mechanisms of CXCL12 induced cell migration and the importance of different signalling cascades that become activated by CXCR4 in leukemic cells versus breast cancer cells. We identified Src kinase as being essential for cell migration in both cancer types, with strong involvement of the Raf/MEK/ERK1/2 pathway. We did not detect any involvement of Ras or JAK2/STAT3 in CXCL12 induced migration in Jurkat cells. Preventing PKC activation with inhibitors does not affect migration in Jurkat cells at all, unlike in the adherent breast cancer cell line MCF-7 cells. However, in both cell lines, knock down of PKCα prevents migration towards CXCL12, whereas the expression of PKCζ is less crucial for migration. PI3K activation is essential in both cell types, however LY294002 usage in MCF-7 cells does not block migration significantly. These results highlight the importance of verifying specific signalling pathways in different cell settings and with different approaches.