[365 Days in Newly Opened Cancer Treatment Center in Core Hospital of Mountainous Area].

The declining birthrate and aging population is one of the social issues in mountainous area in Japan. One regional core hospital at Aizu area in Fukushima prefecture opened cancer treatment center in these area in July, 2022. A high-performance radiation therapy system was newly installed and operated with the staff of Fukushima Medical University, and several supportive therapy for cancer chemotherapy including appearance care became possible in the center. The patients living in Aizu area can receive advanced treatments including radiation therapy without moving to long-distant bigger cities now. We report multiple preparations and several trials that we have made during one year since the opening of the center.

A Nationwide Epidemiological Survey of Adolescent Patients With Diverse Symptoms Similar to Those Following Human Papillomavirus Vaccination: Background Prevalence and Incidence for Considering Vaccine Safety in Japan.

BACKGROUND: Since June 2013, Japan has suspended proactive recommendation of human papillomavirus (HPV) vaccination due to self-reported diverse symptoms, including pain and motor dysfunction, as possible serious adverse events following immunization. Although these symptoms may be seen in adolescents without HPV vaccination, their frequency, taking into account disease severity, has not been examined. METHODS: A two-stage, descriptive, nationwide epidemiological survey was conducted in 2016, with a 6-month target period from July 1 to December 31, 2015, to estimate the prevalence and incidence of diverse symptoms among Japanese adolescents without HPV vaccination. Participants were 11,037 medical departments in hospitals selected nationwide by stratified random sampling. Eligible patients had to satisfy four criteria: (1) aged 12-18 years upon visiting hospital; (2) having at least one of four symptoms/disorders (pain or sensory dysfunction, motor dysfunction, autonomic dysfunction, or cognitive impairment); (3) symptoms/disorders persisting for at least 3 months; and (4) both criteria (2) and (3) influence attendance at school or work. We then extracted data of patients with diverse symptoms similar to those after HPV vaccination while considering opinions of doctors in charge. RESULTS: Estimated 6-month period prevalence of diverse symptoms among girls aged 12-18 years without HPV vaccination was 20.2 per 100,000. Annual incidence was estimated to be 7.3 per 100,000. CONCLUSION: Adolescent Japanese girls without HPV vaccination also visited hospitals with diverse symptoms similar to those following HPV vaccination. Our findings predict the medical demands for coincident diverse symptoms, which are temporally associated with but not caused by HPV vaccination of Japanese adolescents.

Validation of the Japanese version of the Bath CRPS Body Perception Disturbance Scale for CRPS.

PURPOSE: Body perception disturbance is a common symptom and may be one of the key targets of treatment intervention in complex regional pain syndrome (CRPS). As a comprehensive assessment tool of body perception in patients with CRPS, the Bath Body Perception Disturbance Scale (BPDS) was developed, and its adequate reliability and validity have been reported. However, there is no available Japanese version. Therefore, this study aimed to develop a Japanese version of BPDS (BPDS-J) and to investigate the validity of this scale in Japanese patients with CRPS. METHODS: We developed BPDS-J using a forward-backward method. We then assessed 22 patients with CRPS type 1 of the upper limb using BPDS-J, Brief Pain Inventory (BPI), Tampa Scale for Kinesiophobia (TSK), and a two-point discrimination threshold (TPD) on the middle finger. We investigated the internal consistency of BPDS-J and the correlation between BPDS-J and clinical outcomes as a concurrent validity measure. RESULTS: BPDS-J had good internal consistency (Cronbach's α = 0.73) and was significantly correlated with the TPD ratio (r = 0.65, adjusted p = 0.01) and TSK (r = 0.51, adjusted p = 0.04). CONCLUSIONS: BPDS-J has good internal consistency and concurrent validity for assessing body perception disturbance in Japanese patients with CRPS. Disturbed body perception may be worth evaluating when managing patients with CRPS using BPDS.

Resting-state Amplitude of Low-frequency Fluctuation is a Potentially Useful Prognostic Functional Biomarker in Cervical Myelopathy.

BACKGROUND: Cervical MRI is the standard diagnostic imaging technique for patients with cervical myelopathy. However, the utility of conventional cervical MRI as a predictive biomarker for surgical recovery remains unclear, partly because of the limited information obtained from this anatomically small area. Brain resting-state functional MRI (rs-fMRI) may help identify candidate predictive biomarkers. Two analytical methods that assess local spontaneous brain activity are widely used for rs-fMRI: functional connectivity between two brain regions and amplitude of low-frequency fluctuation (ALFF). In our previous analysis of functional connectivity, we discovered that brain functional connectivity may be a predictive biomarker for neurologic recovery in patients with cervical myelopathy; however, the functional connectivity analysis identified a correlation with only one clinical outcome (the 10-second test). To establish a comprehensive prediction measure, we need to explore other brain biomarkers that can predict recovery of other clinical outcomes in patients with cervical myelopathy. QUESTIONS/PURPOSES: We aimed to (1) elucidate preoperative ALFF alterations in patients with cervical myelopathy and how ALFF changes after surgery, with a focus on postoperative normalization and (2) establish a predictive model using preoperative ALFF by investigating the correlation between preoperative ALFF and postoperative clinical recovery in patients with cervical myelopathy. METHODS: Between August 2015 and June 2017, we treated 40 patients with cervical myelopathy. Thirty patients met our prespecified inclusion criteria, all were invited to participate, and 28 patients opted to do so (93%; 14 men and 14 women; mean age: 67 years). The 28 patients and 28 age- and sex-matched controls underwent rs-fMRI (twice for patients with cervical myelopathy: before and 6 months after cervical decompression surgery). We analyzed the same study population that was used in our earlier study investigating functional connectivity. Controls had none of the following abnormalities: neck or arm pain, visual or auditory disorders, cognitive disorder, structural brain disorder, a history of brain surgery, mental and neurologic disorders, and medications for the central nervous system. We performed ALFF comparisons between preoperative patients with cervical myelopathy and controls, analyzed postoperative ALFF changes in patients with cervical myelopathy, and performed a correlation analysis between preoperative ALFF and clinical recovery in these patients. Clinical outcomes in the cervical myelopathy group were assessed using the 10-second test, the Japanese Orthopaedic Association upper-extremity motor (JOA-UEM) score, JOA upper-extremity sensory score (JOA-UES), and Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire for upper-extremity function (JOACMEQ-UEF) score before and 6 months after surgery, which is when we believe these scores generally reach a plateau. A total of 93% of those enrolled (26 of 28 patients) were analyzed both preoperatively and postoperatively; the other two were lost to follow-up. RESULTS: The cervical myelopathy group had an increase in ALFF in the bilateral primary sensorimotor cortices (right, cluster size = 850 voxels, t-value = 6.10; left, cluster size = 370 voxels, t-value = 4.84) and left visual cortex (cluster size = 556 voxels, t-value = 4.21) compared with the control group. The cervical myelopathy group had a decrease in ALFF in the bilateral posterior supramarginal gyrus (right, cluster size = 222 voxels, t-value = 5.09; left, cluster size = 436 voxels, t-value = 5.28). After surgery, the bilateral sensorimotor cortices (right, cluster size = 468 voxels, t-value = 6.74; left, cluster size = 167 voxels, t-value = 5.40) and left visual cortex (cluster size = 3748 voxels, t-value = 6.66) showed decreased ALFF compared with preoperative ALFF, indicating postoperative normalization of spontaneous brain activities in these regions. However, the bilateral posterior supramarginal gyrus did not show an increase in ALFF postoperatively, although ALFF in this region decreased preoperatively. Greater levels of ALFF at the left and right frontal pole and left pars opercularis of the inferior frontal gyrus before surgery in the cervical myelopathy group were correlated with larger improvements in the JOACMEQ-UEF score 6 months after surgery (r = 0.784; p < 0.001, r = 0.734; p < 0.001 and r = 0.770, respectively; p < 0.001). The prediction formula, based on preoperative ALFF values in the left frontal pole, was as follows: the predicted postoperative improvement in the JOACMEQ-UEF score = 34.6 × preoperative ALFF value - 7.0 (r = 0.614; p < 0.001). CONCLUSIONS: Our findings suggest that preoperative ALFF may be a biomarker for postoperative recovery in that it predicted postoperative JOACMEQ-UEF scores. To establish a comprehensive prediction measure for neurologic recovery in patients with cervical myelopathy, a multicenter study is underway. LEVEL OF EVIDENCE: Level II, diagnostic study.

Smoking is associated with greater pain intensity and pain-related occupational disability in Japanese workers.

PURPOSE: Pain symptom, such as that caused by musculoskeletal disorders, is a major cause of occupational disability. As nicotine intake from smoking increases pain sensitivity, smokers may experience stronger pain and be more likely to experience pain-related disability than non-smokers. The study aim was to examine whether smoking was associated with pain-related occupational disability via pain intensity. METHODS: Participants were 1189 workers with pain aged 20-74 years in Japan. Participants completed a self-report questionnaire, which included a question to measure pain-related occupational disability with ordinal-option: (1) without pain-related disability, (2) pain-related presenteeism, and (3) pain-related absenteeism. An ordinal logistic regression model was used to calculate multivariable-adjusted proportional odds ratios (OR) with 95% confidence intervals (CI) for the prevalence of pain-related occupational disability according to smoking status. A multiple mediation analysis was also conducted to assess whether pain sensitivity mediated the association between smoking and pain-related occupational disability. Adjusted variables were demographic variables, socioeconomic status, work-related psychosocial factors, general psychological factors, and pain duration. RESULTS: Current smoking and pain were associated with pain-related occupational disability compared with non-smoking and pain (multivariable OR 1.78; 95% CI 1.26-2.52). Greater pain intensity partially mediated the association of current smoking and pain with pain-related occupational disability. The mediation rate (indirect/total effect) was 25%. CONCLUSION: Smoking and pain were associated with pain-related occupational disability, partially through greater pain intensity, among Japanese workers.

Evaluating the psychometric properties of two-item and four-item short forms of the Japanese Pain Self-Efficacy Questionnaire: a cross-sectional study.

PURPOSE: The Pain Self-Efficacy Questionnaire is a valid measure assessing self-efficacy in individuals with chronic pain. Short-form versions of the measure have been developed to decrease the assessment burden. However, few studies have evaluated the psychometric properties of the short forms in languages other than English. The aim of this study was to evaluate two 2-item short forms and one 4-item short form of the Japanese Pain Self-Efficacy Questionnaire in terms of internal consistency, criterion validity, structural validity, and construct validity. METHODS: This was a cross-sectional study. Data from 150 individuals with mixed chronic pain at a pain management center in a university hospital were extracted from clinical records and analyzed. The data included the information of the original version and short forms of the Japanese Pain Self-Efficacy Questionnaire, and other pain-related measures assessing pain intensity, pain interference, anxiety, depression and pain catastrophizing. RESULTS: Item statistics supported the item selection for each of the three short forms. All the short forms demonstrated adequate internal consistency and criterion validity. With respect to construct validity, one of the 2-item short forms failed to meet the criterion regarding the change in the magnitude of correlation with a depression scale. The 4-item short form met all the criteria including structural validity. CONCLUSION: The study findings provide evidence for the reliability and validity of 2- and 4-item versions of the Japanese Pain Self-Efficacy Questionnaire for use in clinical and research settings.

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.

Prognostic impact of elevated preoperative C-reactive protein on patients with differentiated thyroid carcinoma.

BACKGROUND: C-reactive protein (CRP) has been reported to be associated with poorer prognosis in various malignancies. However, the relationship between CRP and differentiated thyroid carcinoma (DTC) remains to be elucidated. METHODS: A total of 45 patients, including 32 patients with preoperative DTC and 13 DTC patients with metastatic disease, were included in the study. The relationships between CRP levels and clinicopathological features were retrospectively analyzed. RESULTS: Analysis using a receiver operating characteristic curve revealed a preoperative CRP cutoff value of 0.155 mg/dL. Patients with preoperative CRP ≥ 0.155 mg/dL, those with T3 + T4, those with extrathyroidal invasion, or those with stage II, showed a statistically shorter recurrent-free survival than those with preoperative CRP < 0.155 mg/dL, those with T1 + T2, those without extrathyroidal invasion, or those with stage I (P = 0.001, P = 0.004, P = 0.024, and P = 0.025, respectively). Preoperative CRP ≥ 0.155 mg/dL was an independent prognostic factor for recurrent-free survival in the DTC patients (hazard ratio = 6.334, 95% confidence interval: 1.023-39.234, P = 0.037). The proportion of patients aged ≥55 y, and those with T3 + T4, was statistically higher in those with preoperative CRP ≥ 0.155 mg/dL than in those with preoperative CRP < 0.155 mg/dL (P = 0.037 and P = 0.038, respectively). CONCLUSIONS: Higher preoperative CRP levels have a robust prognostic impact on recurrence-free survival in DTC patients. In addition, higher preoperative CRP levels were associated with age ≥ 55 y and T3 + T4.

Serum transthyretin level is associated with prognosis of patients with gastric cancer.

BACKGROUND: The goal of the present study was to determine whether serum transthyretin level can be used as a novel prognostic biomarker for patients with gastric cancer. PATIENTS AND METHODS: Serum levels of transthyretin were examined before treatment in 42 patients with gastric cancer, 30 of whom underwent curative operation and had their prognostic factors analyzed. RESULTS: In an analysis using a receiver operating characteristic curve, transthyretin was evaluated as a useful biomarker to predict the overall survival of the patients (P = 0.033), and a level of 22.8 mg/dL was determined as the cut off value. The transthyretin levels exhibited statistically significant correlations with total protein (r = 0.598, P < 0.001), albumin (r = 0.626, P < 0.001), and retinol binding protein (r = 0.753, P < 0.001). On the other hand, the transthyretin levels showed statistically significant inverse correlations with tumor size (r = -0.753, P < 0.001) and the numbers of involved lymph nodes (r = -0.453, P = 0.012). The patients with serum transthyretin levels of <22.8 mg/dL showed poorer prognosis than those with levels of ≥22.8 mg/dL (P = 0.033); therefore, serum transthyretin level was an independent prognostic factor for the gastric cancer patients (hazard ratio: 0.420, 95% confidence interval: 0.180-0.985, P = 0.042). CONCLUSIONS: Anthropometric measurement of serum transthyretin can be useful for predicting the prognosis of patients with gastric cancer.

Validation of the Japanese version of the life satisfaction checklist (LiSat-11) in patients with low back pain: A cross-sectional study.

BACKGROUND: Previous studies suggest that life satisfaction assessment using the Life Satisfaction checklist (LiSat-11) is a meaningful outcome measure and may play an important role in setting rehabilitation goals in patients with chronic pain. Until now, there was no Japanese version of this questionnaire, and the psychometric properties of the original version of the LiSat-11 have only been investigated using classical test theory approaches. The objective of the present study was to evaluate the psychometric properties of the LiSat-11-J using Rasch analysis in a sample of Japanese people with low back pain (LBP). METHODS: One hundred and two participants with LBP completed the LiSat-11-J. Concurrent Validity of the LiSat-11-J was investigated by examining the relationships between the LiSat-11-J and clinical valuable. Rasch analysis was used to assess targeting, category ordering, unidimensionality, person fit, internal consistency, and differential item functioning. RESULTS: The LiSat-11-J was significantly correlated with disability, pain-related catastrophizing, fear of movement, anxiety, and depression. The LiSat-11-J targeted the participants with low life satisfaction and had unidimensionality, good internal consistency, and good test-retest reliability. Responses to category 1 ("very dissatisfying") and 2 ("dissatisfying") were disordered. After collapsing these two categories into a single new category, targeting function and category order showed a little improvement. CONCLUSION: The LiSat-11-J has unidimensionality, acceptable internal consistency, good test-retest reliability, and concurrent validity to the assessment of pain-related disability and psychological factors. However, targeting function and category order were not well. These two components showed improvement by rescoring category, but not sufficient. These results suggest that the LiSat-11-J is not well adequate to apply as an assessment tool of life satisfaction to the patients with LBP.

[A Case of Recurrent Colon Cancer with Peritoneal Dissemination Treated with Aflibercept Showing Partial Response for One Year].

We report a case of recurrent colon cancer that achieved partial response with chemotherapy of combined 5-fluorouracil (5-FU), irinotecan, Leucovorin(FOLFIRI), and aflibercept. A 65-year-old man was diagnosed with colon cancer with lymph node metastasis. He underwent surgery, but after 1 year, he had a recurrence of peritoneal dissemination, nodal enlargement, and liver metastases. He received chemotherapy(mFOLFOX plus bevacizumab), but suffered progressive disease. Thereafter, FOLFIRI plus aflibercept was administered, and CT revealed a decrease in peritoneal dissemination after 2 cycles of chemotherapy. After 23 cycles, a PET-CT showed no evidence of the disease. We also examined 9 recent cases treated with aflibercept in terms of Grade 3 and 4 adverse effects, leukopenia, neutropenia, thrombocytopenia, hypertension, and sweating. Placentalderived growth factor(PIGF)has been reported to stimulate macrophages and induce production of IL-6, and thus it promotes inflammation and growth of extant cancer. Among the responses to chemotherapy based on the RECIST criteria, a partial response was significantly higher in patients with a low neutrophil-to-lymphocyte ratio(NLR)(p≤0.05)compared to those with high NLR. As regards the relationship between NLR and OS in patients treated with FOLFIRI plus aflibercept, OS was significantly worse in patients with high NLR than those with low NLR(p≤0.05). NLR may be a useful marker in conjunction with aflibercept treatment.

[A Case of Rectal Colon Cancer with Paraneoplastic Cerebellar Degeneration].

A case complicated with colorectal and prostate cancers in paraneoplastic(subacute)cerebellar degeneration(PCD)is extremely rare. We report a retrospective case of rectal carcinoma with paraneoplastic cerebellar degeneration. A 79-year-old man with Parkinson's disease was unable to walk because of paralysis. Brain MRI showed cerebellar atrophy. He was admitted to our hospital for anal bleeding and was diagnosed with colon cancer. An associated diagnosis of PCD was made. After resection, his paralysis and dysarthria were resolved to the extent of beingable to walk and speak fluently. Brain MP-RAGE showed no findings suggestive of metastasis or atrophy. He was treated surgically, which resulted in a transient improvement in PCD symptoms. Per blood testing, cytokines IL-6 and IL-10 were lower postoperatively. Immunosuppressive levels of myeloid- derived suppressor cells(MDSCs)were lower compared with the preoperative values. Thus, innate immunocompetence and resolution of paralysis followed the surgical intervention.

Current status of cancer immunotherapy for esophageal squamous cell carcinoma.

BACKGROUND: Immunotherapy has become a promising treatment strategy for cancer. Immune checkpoint blockade with anti-CTLA4 mAb and anti-PD-1 mAb has demonstrated clear evidence of objective responses including improved overall survival and tumor shrinkage, driving renewed enthusiasm for cancer immunotherapy in multiple cancer types including esophageal squamous cell carcinoma (ESCC). There are several clinical trials using anti-PD1 mAb for ESCC in early phases and the results are currently promising. RESULTS AND CONCLUSIONS: In this review, recent advances in cancer immunotherapy for ESCC are discussed with particular focus on immune checkpoint inhibitors and cancer vaccine.

Fear-avoidance beliefs are independently associated with the prevalence of chronic pain in Japanese workers.

PURPOSE: Pain is a global public health problem with implications for both personal and social heath. Fear-avoidance beliefs (FABs) have been demonstrated to negatively impact and prolong pain in many Western countries, but little is known about the association between FABs and chronic pain (CP) in Asian countries, including Japan. We examined the relationship between FABs and CP in Japanese white-collar workers, a growing population with a high prevalence of CP. METHODS: Questionnaires and company records were used to gather data from 433 Japanese white-collar workers. Data were related to experience of pain, participant sociodemographic/health/lifestyle characteristics, fear-avoidance beliefs [Tampa Scale for Kinesiophobia (TSK)], work-related psychosocial factors (Brief Job Stress Questionnaire), and depressive illness [Psychological Distress Scale (K6)]. Analysis of covariance and multilevel logistic regression modeling were used to analyze associations between the data while controlling for factors known to influence CP prevalence. RESULTS: Prevalence rate of CP was 11.1% (48 of 433 persons). Adjusted odds ratios for participants with CP significantly increased in participants with high TSK scores, even after adjusting for factors known to influence CP prevalence. CONCLUSION: We found a significant association between high TSK scores and CP in Japanese white-collar workers when controlling for other known factors that influence CP such as work-related psychosocial characteristics and depressive conditions. This finding suggests that FABs are independently associated with prevalence of CP.

[Two Cases of Unresectable Advanced Rectal Cancer with a Long-Term Survival for Which Pathological Complete Response Was Achieved through Neoadjuvant Effective Chemotherapy].

We report 2 unusual cases of Stage IV rectal cancer for which pathological complete response was achieved with neoadjuvant chemotherapy(NAC)consisting of a combination of 5-fluorouracil(5-FU), oxaliplatin, Leucovorin(mFOLFOX6)or irinotecan(FOLFIRI), and bevacizumab, without radiotherapy. Case 1: A 65-year-old man was diagnosed as having rectal cancer with an invasive carcinoma of the prostate and lymph node metastasis. He refused to undergo surgery and received NAC instead. After NAC with mFOLFOX6 and FOLFIRI was performed, CT scan and colonoscopy revealed no evidence of disease. The subsequent result was compatible with a complete pathological response. The patient is currently alive 4 years after the first chemotherapy, without evidence of recurrence and adjuvant chemotherapy. Case 2: A 75-year-old man was diagnosed as having rectal cancer with an invasive carcinoma of the bladder and lymph node metastasis. After providing neoadjuvant bevacizumab-containing chemotherapy, low anterior resection of the rectum was performed. Operative findings showed that the tumor was only ulcer and the lymph nodes were not enlarged. The subsequent results indicated that pathological findings revealed no cancer and a complete pathological response. In conclusion, the survival benefits from NAC are still unclear for patients with an initially unresectable rectal cancer. We report 2 rare cases of rectal cancer with long survival and a complete pathological response after neoadjuvant chemotherapy.

[Three Cases of High-Grade Malignant Cancer of Unknown Primary with a Long-Term Survival].

We report 3unusual cases of cancer of unknown primary(CUP)with a long-term survival after chemotherapy. A 56-yearold man was diagnosed as having CUP with invasion of an enlarged carcinoma 20 cm in size to the pancreas and peritoneal dissemination. He received chemotherapy with paclitaxel, carboplatin, and gemcitabine. After the chemotherapy, CT scan and PET-CT revealed no evidence of disease, so tumor resection was performed. The subsequent pathological findings revealed no cancer and a complete pathological response. The patient is currently alive 4 years after the first surgery, without evidence of recurrence and adjuvant chemotherapy. A 60-year-old man was diagnosed as having CUP with an undifferentiated carcinoma and lymph node metastasis. He received chemotherapy with paclitaxel, carboplatin, and gemcitabine. However, unanticipated adverse events(finger ulcer)occurred. Thus, the chemotherapy was changed to paclitaxel, carboplatin, and etoposide. The patient is currently alive 4.2 years after the first chemotherapy, without evidence of recurrence. A 59-year-old man was diagnosed as having CUP with neuroendocrine carcinoma(NEC)and lymph node metastasis. He received chemotherapy with irinotecan and cisplatin. The lymph node metastases disappeared, but bone metastasis was found. The chemotherapy was changed to paclitaxel, carboplatin, and etoposide. The patient is currently alive 3.5 years after the first chemotherapy, without evidence of recurrence. We report 3rare cases of high-grade malignant CUP with complete pathological response, partial response, stable disease, and long-term survival after chemotherapy.

Go-sha-jinki-Gan (GJG) ameliorates allodynia in chronic constriction injury-model mice via suppression of TNF-α expression in the spinal cord.

BACKGROUND: Alternative medicine is noted for its clinical effect and minimal invasiveness in the treatment of neuropathic pain. Go-sha-jinki-Gan, a traditional Japanese herbal medicine, has been used for meralgia and numbness in elderly patients. However, the exact mechanism of GJG is unclear. This study aimed to investigate the molecular mechanism of the analgesic effect of GJG in a chronic constriction injury model. RESULTS: GJG significantly reduced allodynia and hyperalgesia from the early phase (von Frey test, p<0.0001; cold-plate test, p<0.0001; hot-plate test p»0.011; two-way repeated measures ANOVA). Immunohistochemistry and Western blot analysis revealed that GJG decreased the expression of Iba1 and tumor necrosis factor-a in the spinal cord. Double staining immunohistochemistry showed that most of the tumor necrosis factor-a was co-expressed in Iba1-positive cells at day 3 post-operation. GJG decreased the phosphorylation of p38 in the ipsilateral dorsal horn. Moreover, intrathecal injection of tumor necrosis factor-a opposed the anti-allodynic effect of GJG in the cold-plate test. CONCLUSIONS: Our data suggest that GJG ameliorates allodynia in chronic constriction injury model mice via suppression of tumor necrosis factor-a expression derived from activated microglia. GJG is a promising drug for the treatment of neuropathic pain induced by neuro-inflammation.

Arthropathy-related pain in a patient with congenital impairment of pain sensation due to hereditary sensory and autonomic neuropathy type II with a rare mutation in the WNK1/HSN2 gene: a case report.

BACKGROUND: Hereditary sensory and autonomic neuropathy (HSAN) type II with WNK1/HSN2 gene mutation is a rare disease characterized by early-onset demyelination sensory loss and skin ulceration. To the best of our knowledge, no cases of an autonomic disorder have been reported clearly in a patient with WNK/HSN2 gene mutation and only one case of a Japanese patient with the WNK/HSN2 gene mutation of HSAN type II was previously reported. CASE PRESENTATION: Here we describe a 54-year-old woman who had an early childhood onset of insensitivity to pain; superficial, vibration, and proprioception sensation disturbances; and several symptoms of autonomic failure (e.g., orthostatic hypotension, fluctuation in body temperature, and lack of urge to defecate). Genetic analyses revealed compound homozygous mutations in the WNK1/HSN2 gene (c.3237_3238insT; p.Asp1080fsX1). The patient demonstrated sensory loss in the "stocking and glove distribution" but could perceive visceral pain, such as menstrual or gastroenteritis pain. She experienced frequent fainting episodes. She had undergone exenteration of the left metatarsal because of metatarsal osteomyelitis at 18 years. Sural nerve biopsy revealed a severe loss of myelinated and unmyelinated nerves. She complained of severe pain in multiple joints, even on having pain impairment. Although non-steroidal anti-inflammatory drugs are generally more effective than acetaminophen for arthritis, in our case, they were ineffective and acetaminophen (2400 mg/day) adequately controlled her pain and improved quality of life. Over 3 months, the numerical rating scale, pain interference scale of the Brief Pain Inventory, and the Pain Catastrophizing Scale decreased from 6/10 to 3/10, from 52/70 to 20/70, and from 22/52 to 3/52 points, respectively. CONCLUSIONS: This is the second reported case of a Japanese patient with WNK/HSN2 gene mutation of HSAN type II and the first reported case of an autonomic disorder in a patient with the WNK/HSN2 gene mutation. Acetaminophen adequately controlled arthropathy related pain in a patient with congenital impairment of pain sensation.

Socioeconomic value of intervention for chronic pain.

PURPOSE: The purpose of this study was to examine the cost-effectiveness of pain treatments in two pain centers in Japan. METHODS: The study population comprised 91 patients receiving various treatments for chronic pain, which were divided into three categories: (1) medication, (2) medication + nerve block, and (3) other modalities (exercise and/or pain education). Pain was assessed using the Pain Disability Assessment Scale (PDAS) score, Hospital Anxiety and Depression Scale (HADS) score, Pain Catastrophizing Scale (PCS) score, and EQ-5D score. First, the reliability of the EQ-5D score first assessed by evaluating the correlation this score with those of the other pain-related evaluation instruments, and then the cost effectiveness of the pain treatments was evaluated. Evaluation of medical costs was based on data provided from the Management Services of the hospital, which in turn were based on national health scheme medical treatment fees. The quality-adjusted life year (QALY) value was calculated from the EQ-5D score, converted to 12 months, and then used for cost-benefit analysis along with medical treatment fees. RESULTS: According to the recent IASP classification, more patients had chronic neuropathic pain (41) than chronic primary pain (37 patients) or chronic musculoskeletal pain (27 patients). There was a significant correlation between the EQ-5D score and the PDAS, HADS, and PCS scores, which demonstrated the reliability of the EQ-5D score. Significant improvement in the HADS, PCS, and EQ-5D scores was noted after 3 months of pain treatment. Calculation of the cost-effectiveness based on the estimated annual medical treatment cost and QALY revealed a mean value of US $45,879 ± 103,155 per QALY (median US $16,903), indicating adequate socioeconomic utility. CONCLUSION: Based on our results, the EQ-5D is reliable for evaluating chronic pain in patients. The medico-economic balance was appropriate for all treatments provided in two comprehensive pain centers in Japan.

Pain-Related Brain Activity Evoked by Active and Dynamic Arm Movement: Delayed-Onset Muscle Soreness as a Promising Model for Studying Movement-Related Pain in Humans.

OBJECTIVE: To demonstrate delayed-onset muscle soreness (DOMS) is a suitable model for the study of movement-evoked pain, we attempted to identify brain regions specifically involved in pain evoked by active and dynamic movement under DOMS condition. SUBJECT: Twelve healthy volunteers METHODS: DOMS was induced in the left upper-arm flexor muscles by an eccentric elbow contraction exercise. Movement-evoked pain in the affected muscles was evaluated just before (day 0) and after (days 1-7 and 30) the exercise using a visual analog scale. Subjects underwent functional magnetic resonance imaging scans while performing repeated elbow flexion on day 2 (DOMS condition) and day 30 (painless condition). We compared brain activity between the DOMS and painless conditions. RESULTS: Movement-evoked pain reached peak intensity on day 2 and disappeared by day 30 in all subjects. No subject felt pain at rest on either of these days. Contralateral primary motor cortex (M1), parietal operculum and bilateral presupplementary motor area (pre-SMA) showed greater activity during active and dynamic arm movement with DOMS than during the same movement without pain. There was no difference in activation of brain regions known collectively as the "pain matrix," except for the parietal operculum, between the two conditions. CONCLUSION: Active and dynamic movement with pain selectively evoked activation of M1, pre-SMA, and parietal operculum, as assessed using DOMS. Our results demonstrate that DOMS is a promising experimental model for the study of movement-evoked pain in humans.