清水 啓介

Co-administration of mirogabalin besylate and nonsteroidal anti-inflammatory drugs is effective for neuropathic pain; however, mechanism of its action remains unknown. We aimed to evaluate the mechanism of this synergistic effect of the concomitant administration for neuropathic pain using chronic constriction injury model rats. Fifty male Wister rats of 7-week-old were used. Right sciatic nerve ligation was performed in 40 rats and they were sub-divided into four groups: vehicle, mirogabalin, diclofenac sodium and co-administration of them. Ten rats underwent sham surgery. Fluorogold was attached to sciatic nerve during surgery. Von Frey filament and weight bearing tests were performed on postoperative Day 6 as behavioral assessments and drug was administrated intraperitoneally. Half rats in each group underwent behavioral assessment and perfusion fixation using 4% paraformaldehyde on postoperative Day 7 and remaining on postoperative Day 14. Subsequently, dorsal root ganglion at L4 to L6 was collected and examined immunohistochemistry for calcitonin gene-related peptide, and their immunoreactivity in fluorogold-labeled neurons was measured. Spinal cord at lumbar swelling was resected, immunostained for ionized-calcium-binding adapter molecule-1 and glial fibrillary acidic protein, and immunoreactive neurons in dorsal horn of spinal cords were calculated as the occupancy of them. Mirogabalin suppresses the neuropeptide-release from presynaptic afferent neuron directly and it resulted in suppressing glia cells activation. Diclofenac sodium inhibits cyclooxygenase-2 and prostaglandin production, related to allodynia. These effects of mirogabalin and diclofenac sodium, respectively, inhibited glia cells strongly, which is presumed to be one of the mechanisms for the effectiveness of their co-administration for neuropathic pain.

Abstract The lifetime prevalence of low back pain is 83%. Since there is a lack of evidence for therapeutic effect by cognitive behavioral therapy (CBT) or physical therapy (PT), it is necessary to develop objective physiological indexes and effective treatments. We conducted a prospective longitudinal study to evaluate the treatment effects of CBT, PT, and neurofeedback training (NFT) during alpha wave NFT. The early-chronic cases within 1 year and late-chronic cases over 1 year after the diagnosis of chronic low back pain were classified into six groups: Controls, CBTs, PTs, NFTs, CBT-NFTs, PT-NFTs. We evaluated the difference in EEG, psychosocial factors, scores of low back pain before/after the intervention. Therapeutic effect was clearly more effective in the early-chronic cases. We found that the intensity of alpha waves increased significantly after therapeutic intervention in the NFT groups, but did not have the main effect of reducing low back pain; the interaction between CBT and NFT reduced low back pain. Factors that enhance therapeutic effect are early intervention, increased alpha waves, and self-efficacy due to parallel implementation of CBT/PT and NFT. A treatment protocol in which alpha wave neurofeedback training is subsidiarily used with CBT or PT should be developed in the future.

Abstract This study examined the factors that inhibit the therapeutic effects of cognitive behavioral therapy (CBT) and clarify the adaptation judgment criteria of CBT. We included patients with chronic low back pain and allocated them to the adaptation (with visual analog scale [VAS] improvement) or non-adaptation group (without VAS improvement). The patients were analyzed using various psychological tests. CBT improved depressive symptoms and catastrophic thinking; however, they were not correlated with the VAS and did not directly affect low back pain improvement. The non-adaptation group showed an unexplainable/vague sense of anxiety; an excessive focus on searching for pain; a strong intimacy desire; a strong tendency of medical dependency; and fantasy or distortion of the actual experience, especially self-image. Moreover, the patients showed a low ability to objectively express or attribute meaning to pain due to poor language skills, attention-deficit hyperactivity disorder, and emotional value judgment. Individuals with the aforementioned characteristics of pre-CBT psychological tests should select a different treatment approach given the high poor-adaption possibility. Even patients with depressive or anxious symptoms are not necessarily adaptable for CBT. Therefore, pre-CBT tests for treatment suitability are necessary. Future studies should establish a protocol for psychotherapy suitable for the non-adaptation group.

Objective: In recent years, there has been an increase in research on the therapeutic effects of exergaming, but there have been few studies on these types of interventions for chronic low back pain. In this study, we hypothesized that the Nintendo Ring Fit Adventure (RFA) exergame would be effective for patients with chronic low back pain, and we conducted a randomized prospective longitudinal study.Materials and Methods: Patients with chronic low back pain were included in this study. Twenty randomly selected patients (9 males and 11 females, mean age 49.3 years) were included in the RFA group, and RFA exergaming was performed once a week for 40 minutes for 8 weeks. Twenty patients (12 males and 8 females, mean age 55.60 years) served as the control group and received oral treatment for 8 weeks. Pain and psychological scores (pain self-efficacy, pain catastrophizing, and kinesiophobia) were measured and analyzed before and after 8 weeks of treatment in both groups.Results: In the RFA group, low back pain, buttock pain, and pain self-efficacy were significantly improved after 8 weeks of RFA exergaming, but there was no significant improvement in lower limb numbness, pain catastrophizing, or kinesiophobia. In the control group, no significant improvement was observed after 8 weeks of oral treatment.Conclusion: RFA exergaming increased pain self-efficacy and reduced pain in patients with chronic low back pain. Future treatment protocols should be developed to improve pain self-efficacy.

Background: Indications for subthalamic nucleus deep brain stimulation (STN-DBS) surgery are determined basically by preoperative motor function; however, postoperative quality of life (QOL) is not necessarily associated with improvements in motor symptoms, suggesting that neuropsychiatric symptoms might be related to QOL after surgery in patients with Parkinson's disease. Objectives: We aimed to examine temporal changes in neuropsychiatric symptoms and their associations with QOL after STN-DBS. Materials and Methods: We prospectively enrolled a total of 61 patients with Parkinson's disease (mean age = 65.3 ± 0.9 years, mean disease duration = 11.9 ± 0.4 years). Motor function, cognitive function, and neuropsychiatric symptoms were evaluated before and after DBS surgery. Postoperative evaluation was performed at 3 months, 1 year, and 3 years after surgery. Results: Of the 61 participants, 54 completed postoperative clinical evaluation after 3 months, 47 after 1 year, and 23 after 3 years. Frontal lobe functions, depression, and verbal fluency significantly worsened 3 years after STN-DBS. Non-motor symptoms such as impulsivity and the Unified PD Rating Scale (UPDRS) part I score were associated with QOL after STN-DBS. Conclusions: Frontal lobe functions, depression, and verbal fluency significantly worsened 3 years after STN-DBS. The UPDRS part I score and higher impulsivity might be associated with QOL after STN-DBS.

<b><i>Introduction:</i></b> This study aimed to use a novel MRI contrast, the standardized T1-weighted/T2-weighted (sT1w/T2w) ratio, to assess damage of the white matter and gray matter in multiple system atrophy (MSA). Furthermore, this study investigated whether the sT1w/T2w ratio was associated with cognitive impairment in MSA. <b><i>Methods:</i></b> The white matter and gray matter sT1w/T2w ratio of 37 MSA patients and 19 healthy controls were measured. Correlation analyses were used to evaluate the relationship between sT1w/T2w ratio values and clinical variables, and a multivariate analysis was used to identify independent factors associated with cognitive impairment in MSA. <b><i>Results:</i></b> MSA patients showed a higher white matter sT1w/T2w ratio value than controls (<i>p</i> < 0.001), and the white matter sT1w/T2w ratio value was significantly correlated with the International Cooperative Ataxia Rating Scale score (<i>r</i> = 0.377, <i>p</i> = 0.021) and the Addenbrooke’s cognitive examination III score (<i>r</i> = −0.438, <i>p</i> = 0.007). Cognitively impaired MSA patients had a significantly higher white matter sT1w/T2w ratio value than cognitively preserved MSA patients (<i>p</i> = 0.010), and the multiple logistic regression analysis revealed that the median white matter sT1w/T2w ratio value was independently associated with cognitive impairment in MSA. <b><i>Conclusion:</i></b> The sT1w/T2w ratio is sensitive to degenerative changes in the white matter that is associated with cognitive ability in MSA patients.

<b><i>Introduction:</i></b> Early-onset dementia (EOD), defined as dementia onset before the age of 65 years, is relatively rare, but its social impacts are significant. This study aimed to characterize the diagnosis and clinical and social status of EOD subjects in the 11 dementia centers in Chiba Prefecture, Japan. <b><i>Methods:</i></b> A retrospective 1-year survey was conducted. Collected data included clinical diagnosis, age at onset, age at survey, neuropsychological test, family history, employment, and living status. <b><i>Results:</i></b> We identified 208 EOD subjects, including 123 (59.4%), 24 (11.6%), 21 (10.1%), 17 (8.2%), and 10 (4.8%) with Alzheimer’s disease (AD), vascular dementia, frontotemporal lobar degeneration (FTLD), dementia with Lewy bodies/Parkinson’s disease dementia, and alcohol-related dementia, respectively. The Mini-Mental State Examination (MMSE) score <24 was observed in 50–75% of patients and was not correlated with disease duration. Twenty-four (16.4%) subjects had positive family history of EOD. EOD subjects were at risk of early retirement, and 133 subjects lived with their family, in whom 64 (30.8%) lived with their child. <b><i>Conclusion:</i></b> In dementia centers, AD, FTLD, and Lewy body dementia had relatively large proportion. Employment, economy, and social supports are urgently needed for EOD subjects and their family.