Association between neuropathic pain characteristics and DNA methylation of transient receptor potential ankyrin 1 in human peripheral blood.

Elucidation of epigenetic mechanisms correlating with neuropathic pain in humans is crucial for the prevention and treatment of this treatment-resistant pain state. In the present study, associations between neuropathic pain characteristics and DNA methylation of the transient receptor potential ankyrin 1 (TRPA1) gene were evaluated in chronic pain patients and preoperative patients. Pain and psychological states were prospectively assessed in patients who suffered chronic pain or were scheduled for thoracic surgery. Neuropathic characteristics were assessed using the Douleur Neuropathique 4 (DN4) questionnaire. DNA methylation levels of the CpG islands in the TRPA1 gene were examined using whole blood. Forty-eight adult patients were enrolled in this study. Increases in DNA methylation rates at CpG -51 showed positive correlations with increases in the DN4 score both in preoperative and chronic pain patients. Combined methylation rates at CpG -51 in these patients also significantly increased together with increase in DN4 scores. Neuropathic pain characteristics are likely associated with methylation rates at the promoter region of the TRPA1 gene in human peripheral blood.

Neuropathic Characteristics In Patients With Persistent Idiopathic Facial Pain.

BACKGROUND: Persistent idiopathic facial pain (PIFP) is a subtype of painful cranial neuropathies and other facial pains. The involvement of neuropathic mechanisms in PIFP, however, remains controversial. Using the Douleur Neuropathique 4 (DN4) questionnaire, the present study examined neuropathic characteristics in patients with PIFP. METHODS: The multi-institutional retrospective study collected the following clinical data from 205 consecutive patients with adult chronic pain: gender, age, BMI, diseases causing chronic pain, disease duration, visual analogue scale score of pain strength, and DN4 score. To compare neuropathic characteristics between PIFP and postherpetic neuralgia (PHN), we selected patients with PIFP (n=19) and patients with PHN (n=33), and performing a case-control study in which each patient with PHN or PIFP was matched by age and gender (n=16 in each group). RESULTS: DN4 score was significantly lower in the PIFP group than in the PHN group before and after matching. The incidence when DN4 was ≥4 was 10.5% before matching and 12.5% after matching in the PIFP group, both of which were significantly lower than those in the PHN group before and after matching (66.7% and 75.0%). CONCLUSION: Ten percent of the PIFP patients likely show neuropathic pain characteristics.

A Cross-Cultural Validation of the Multidimensional Pain Readiness to Change Questionnaire 2 for Japanese Individuals With Chronic Pain.

OBJECTIVES: The Multidimensional Pain Readiness to Change Questionnaire 2 (MPRCQ2) is a reliable and valid measure that assesses readiness to adopt a variety of discrete pain self-management responses. We sought to translate and evaluate psychometric properties of the Japanese version of the MPRCQ2 (MPRCQ2-J) in individuals with chronic pain. METHODS: One hundred seventy-three individuals with chronic pain were asked to complete the MPRCQ2-J, as well as measures assessing pain intensity, pain interference, self-efficacy, and general readiness to adopt a self-management approach for pain. Forty-eight of these participants provided additional MPRCQ2-J data to assess test-retest reliability. RESULTS: The findings supported a 2-factor structure of the MPRCQ2-J when error covariances between the some of the nine primary scales were allowed. Adequate internal consistencies of the MPRCQ2-J scales (Cronbach's α ranged 0.71 to 0.86), except for the total score (α = 0.68), were observed. However, adequate test-retest reliabilities (intraclass correlation coefficients ≥ 0.60) were found for only 59% of the MPRCQ2-J scales. The MPRCQ2-J evidenced its construct validity via confirmation of the predicted patterns of associations with validity criterion measures and the anticipated effects of participation in an exercise treatment. DISCUSSION: The findings support the internal consistency (except for the total score) and construct validity for MPRCQ2-J scales. However, potential limitations with respect to test-retest reliability of some of the scales were also suggested. The MPRCQ2-J can be used to examine the role that specific readiness domains of pain self-management responses may play in an adjustment process in Japanese individuals with chronic pain.

The Relationships Between Pain-Catastrophizing Subcomponents and Multiple Pain-Related Outcomes in Japanese Outpatients with Chronic Pain: A Cross-Sectional Study.

OBJECTIVES: The present study sought to examine associations between the pain-catastrophizing subcomponents and multiple pain-related outcomes in Japanese individuals with chronic pain. METHODS: A cross-sectional study design was employed with 213 chronic pain outpatients. The participants were recruited from 3 units at a university hospital and from a pain clinic at a municipal hospital. Study measures were used to assess pain catastrophizing, anxiety, depression, pain interference, and pain severity. RESULTS: Path analysis with multiple pain-related outcomes while controlling for age and gender revealed that the Helplessness subcomponent was associated with anxiety, depression, pain interference, and pain severity. The Magnification subcomponent was related to anxiety and depression, and the Rumination subcomponent accounted for the variance of pain interference. DISCUSSION: The present results suggested the important role of helplessness across cultural backgrounds. It also provides guidance on the application of cognitive behavioral techniques for chronic pain management in Japan.

Reliability and validity of the Japanese translation of the DN4 Diagnostic Questionnaire in patients with neuropathic pain.

BACKGROUND: The Douleur Neuropathique 4 questionnaire (DN4) is a simple and objective tool developed by the French Neuropathic Pain Group to screen for neuropathic pain. METHODS: This prospective observational study was undertaken in three hospitals to assess the validity of a Japanese translation of the DN4. We first translated the DN4 into Japanese using a forward-backward method. Pain specialists then examined patients independently and diagnosed them with neuropathic or non-neuropathic pain, according to the International Association for the Study of Pain definitions. The Japanese version of the DN4 questionnaire was then given to each patient. RESULTS: Of 187 patients that met our inclusion criteria, 100 and 87 were diagnosed with neuropathic and non-neuropathic pain, respectively. The test-retest intra-class correlation coefficient (95% confidence interval) was 0.827 (0.769-0.870). Among patients with identical diagnoses of neuropathic or non-neuropathic pain, receiver-operating characteristic curve analysis revealed an area under the curve of 0.89. A cut-off point of equal or greater than 4 resulted in a sensitivity of 71% and specificity of 92%. CONCLUSION: The Japanese version of the DN4 was found to be a helpful tool for discriminating between neuropathic and non-neuropathic pain.

Validity, reliability, and assessment sensitivity of the Japanese version of the short-form McGill pain questionnaire 2 in Japanese patients with neuropathic and non-neuropathic pain.

OBJECTIVE: The objective of this study was to define the validity, reliability, and assessment sensitivity of the Japanese version of the Short-Form McGill Pain Questionnaire 2 (SF-MPQ-2-J). DESIGN: This is a cross-sectional study. PATIENTS AND METHODS: The original SF-MPQ-2 was translated into Japanese to create the SF-MPQ-2-J, and the cross-cultural equivalence of assessment tool for Japanese patients was validated. The reliability of the SF-MPQ-2-J was assessed using internal consistency, reliability coefficients (Cronbach's α), and reproducibility coefficients (intraclass correlation coefficient) obtained using 234 patients with chronic pain. SF-MPQ-2-J validity was assessed based on associations identified between total and subscale scores compared with other assessment methods. A confirmatory factor analysis (CFA) was also performed to test the theoretical structure of the SF-MPQ-2-J. RESULTS: The internal consistencies calculated included continuous pain, α=0.893; intermittent pain, α=0.875; predominantly neuropathic pain, α=0.917; affective descriptors, α=0.857; and total score, α=0.907. The reproducibility coefficients calculated included continuous pain, ρ=0.81; intermittent pain, ρ=0.78; predominantly neuropathic pain, ρ=0.85; affective descriptors, ρ=0.75; and total score, ρ=0.83. The CFA showed that the model fit of the readily interpretable subscales was acceptable, and the goodness of fit index value was 0.917. In addition, the mean predominantly neuropathic pain subscale score was found to be significantly higher for patients with neuropathic pain vs non-neuropathic pain. CONCLUSION: These findings suggest that the reliability and validity of the SF-MPQ-2-J are excellent, and the SF-MPQ-2-J represents a cross-cultural equivalent to SF-MPQ-2. Consequently, the latter is suitable for research and clinical use, and for discriminating neuropathic pain from non-neuropathic pain.

Validation of the Japanese version of the pain self-efficacy questionnaire in Japanese patients with chronic pain.

OBJECTIVES: The present study aimed to develop the Japanese version of the Pain Self-Efficacy Questionnaire (PSEQ-J) and to evaluate its psychometric properties. DESIGN: Cross-sectional design. SETTING: A pain clinic, a neurosurgery unit, and an orthopedic surgery unit in one university hospital and a pain clinic in a municipal hospital. METHODS: One hundred and seventy-six participants completed study measures, which included 1) the PSEQ-J, 2) the Hospital Anxiety and Depression Scale, 3) the Pain Catastrophizing Scale, 4) the Medical Outcome Study Short-Form 36, 5) the Pain Disability Assessment Scale, and 6) the Short-Form McGill Pain Questionnaire. RESULTS: The PSEQ-J demonstrated adequate reliability and validity. Hierarchical multiple regression analyses showed that pain self-efficacy as measured with the PSEQ-J accounted for a significant proportion of the variance on the measures administered in the present study. The PSEQ-J was most strongly associated with social activity. CONCLUSIONS: The results demonstrated that the PSEQ-J has adequate psychometric properties, supporting its use in clinical and research settings and suggest that the PSEQ-J may be particularly strongly associated with more social and less physical activity.

Human brain activity associated with painful mechanical stimulation to muscle and bone.

PURPOSE: The purpose of this study was to elucidate the central processing of painful mechanical stimulation to muscle and bone by measuring blood oxygen level-dependent signal changes using functional magnetic resonance imaging (fMRI). METHODS: Twelve healthy volunteers were enrolled. Mechanical pressure on muscle and bone were applied at the right lower leg by an algometer. Intensities were adjusted to cause weak and strong pain sensation at either target site in preliminary testing. Brain activation in response to mechanical nociceptive stimulation targeting muscle and bone were measured by fMRI and analyzed. RESULTS: Painful mechanical stimulation targeting muscle and bone activated the common areas including bilateral insula, anterior cingulate cortex, posterior cingulate cortex, secondary somatosensory cortex (S2), inferior parietal lobe, and basal ganglia. The contralateral S2 was more activated by strong stimulation than by weak stimulation. Some areas in the basal ganglia (bilateral putamen and caudate nucleus) were more activated by muscle stimulation than by bone stimulation. CONCLUSIONS: The putamen and caudate nucleus may have a more significant role in brain processing of muscle pain compared with bone pain.