Estimation of cognitive impairment in chronic pain patients and characteristics of estimated mild cognitive impairment.

Background: Patients with chronic pain suffer from psychological effects such as anxiety due to the pain itself. Pain can not only impair activities of daily living (ADL) and quality of life (QOL), but also impair cognitive function. Therefore, in this study, we aimed to estimate the cognitive function of chronic pain patients using a deep neural network (DNN) model that has already been implemented in society. We investigated the characteristics of patients presumed to have mild cognitive impairment (MCI) and, at the same time, verified the relationship with the questionnaire commonly used in chronic pain research, which is administered by 43 university affiliated hospitals and medical institutions participating in the chronic pain research group of the Ministry of Health, Labor and Welfare in Japan (assessment batteries). Method: The study included 114 outpatients from a multidisciplinary pain clinic, and we estimated their Mini-Mental State Examination (MMSE) scores based on age and basic blood test data (23 items). Furthermore, we classified the estimated MMSE scores of chronic pain patients into two groups based on a cutoff score of 27, which indicates MCI, and compared the blood data and assessment batteries. Additionally, we used a control group of 252 healthy adults aged 45 years or older who visited a dementia prevention outpatient clinic for comparison with the MMSE scores of chronic pain patients. Result: The MMSE scores in chronic pain patients were below the cutoff for MCI. When classified into two groups based on the estimated MMSE score of 27 points, WBC, RBC, Hb, Hct, PLT, UA, BUN, creatinine, Triglyceride, and γ-GT were significantly higher in the blood data. In the MCI group, PDAS values were significantly lower. Furthermore, only in the non-MCI group, a significant correlation was found between the estimated MMSE value and BPI, PDAS, and Locomo. The estimated MMSE scores were significantly lower in chronic pain patients than in healthy adults (p = 0.04). Conclusion: Patients with chronic pain may exhibit cognitive impairment due to systemic metabolic disturbances. This suggests that chronic pain affects activities of daily living, resulting in systemic metabolic disorders.

[Role of Pain Clinics in Chronic Pain Management].

A pain clinic is a medical care center that specializes in pain management and does not only provide nerve block therapy. Pain specialists diagnose the etiology of pain based on the biopsychosocial model of pain and develop individualized treatment goals for patients at the pain clinic. Appropriate treatment methods are selected and implemented to achieve these goals. The primary goal of treatment is not merely pain relief but improved activities of daily living/quality of life. Therefore, a multidisciplinary approach is important.

Preß1-high-density lipoprotein metabolism is delayed in patients with chronic kidney disease not on hemodialysis.

BACKGROUND: Preß1-high-density lipoprotein (HDL) is a lipid-poor cholesterol acceptor that is converted to lipid-rich HDL by lecithin-cholesterol acyltransferase (LCAT). In patients receiving hemodialysis, preß1-HDL metabolism is hampered even if HDL cholesterol is normal. Hemodialysis may affect preß1-HDL metabolism by releasing lipases from the vascular wall due to heparin. OBJECTIVES: We investigated whether preß1-HDL metabolism is delayed in patients with chronic kidney disease (CKD) who are not receiving hemodialysis. METHODS: We examined 44 patients with Stage 3 or higher CKD and 22 healthy volunteers (Control group). The patients with CKD were divided into those without renal replacement therapy (CKD group, n = 22) and those undergoing continuous ambulatory peritoneal dialysis (CAPD group, n = 22). Plasma preß1-HDL concentrations were determined by immunoassay. During incubation at 37°C, we used 5,5-dithio-bis (2-nitrobenzoic acid) (DTNB) to inhibit LCAT activity and defined the conversion halftime of preß1-HDL (CHTpreß1) as the time required for the difference in preß1-HDL concentration in the presence and absence of 5,5-DTNB to reach half the baseline concentration. RESULTS: The absolute and relative preß1-HDL concentrations were higher, and CHTpreß1 was longer in the CKD and CAPD groups than in the Control group. Preß1-HDL concentration was significantly correlated with CHTpreß1 but not with LCAT activity in patients with CKD and CAPD. CONCLUSION: Preß1-HDL metabolism is delayed in patients with CKD who are not on hemodialysis. This preß1-HDL metabolic delay may progress as renal function declines.

Pilot study of a basic individualized cognitive behavioral therapy program for chronic pain in Japan.

BACKGROUND: Chronic pain is a major health problem, and cognitive behavioral therapy (CBT) is its recommended treatment; however, efforts to develop CBT programs for chronic pain and assess their feasibility are remarkably delayed in Asia. Therefore, we conducted this pilot study to develop a basic individualized CBT for chronic pain (CBT-CP) and assessed its feasibility for use in Japan. METHODS: Our study was an open-labeled before-after trial without a control group conducted cooperatively in five Japanese tertiary care hospitals. Of 24 outpatients, 15, age 20-80, who experienced chronic pain for at least three months were eligible. They underwent an eight-session CBT-CP consisting of relaxation via a breathing method and progressive muscle relaxation, behavioral modification via activity pacing, and cognitive modification via cognitive reconstruction. The EuroQol five-dimensional questionnaire five level (EQ5D-5 L) assessment as the primary outcome and quality of life (QOL), pain severity, disability, catastrophizing, self-efficacy, and depressive symptoms as secondary outcomes were measured using self-administered questionnaires at baseline, post-treatment, and 3-month follow-up. Intention-to-treat analyses were conducted. RESULTS: Effect size for EQ5D-5 L score was medium from baseline to post-treatment (Hedge's g = - 0.72, 90% confidence interval = - 1.38 to - 0.05) and up to the 3-month follow-up (g = - 0.60, CI = - 1.22 to 0.02). Effect sizes for mental and role/social QOL, disability, catastrophizing, self-efficacy, and depressive symptoms were medium to large, although those for pain severity and physical QOL were small. The dropout rate was acceptably low at 14%. No severe adverse events occurred. CONCLUSION: The findings suggest that CBT-CP warrants a randomized controlled trial in Japan. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), UMIN000020880. Registered on 04 February 2016.

Preparation of Ordered Mesoporous Au using Double Gyroid Mesoporous Silica KIT-6 via a Seed-Mediated Growth Process.

Ordered mesoporous Au was prepared using double gyroid (cubic Ia-3d) mesoporous silica KIT-6 as a template. The Au frameworks were formed within the template via a seed-mediated growth process. Au nanoparticles were initially prepared as seeds within the mesopores, and subsequently, they were grown under mild and controlled reducing conditions. The transmission electron micrographs and scanning electron micrographs of mesoporous Au after the removal of the template revealed the formation of mesoporous Au replicas. The small-angle X-ray scattering pattern of mesoporous Au reveals that the obtained mesoporous Au has a cubic I41 32 mesostructure, which is different from that of the original template, implying that Au was deposited within only one mesochannel of the two interconnected ones. The seed-mediated growth process is a key factor in the successful formation of ordered mesoporous Au using a mesoporous silica template. Our preparative method can serve as a guide for further development of synthetic and materials chemistry of mesoporous Au.

The Effect of Guidance regarding Home Exercise and ADL on Adolescent Females Suffering from Adverse Effects after HPV Vaccination in Japanese Multidisciplinary Pain Centers.

Background. Two prophylactic papillomavirus (HPV) vaccines have been available for primary prevention of cervical cancer. Although serious adverse effects (AE) were rare, more than 230 women have been suffering from severe AEs such as persistent pain and headache in Japan. Our research group started to treat adolescent females suffering from the AEs. Objective. To survey the characteristics of and the effects of cognitive behavioral therapy on adolescent female suffering from the AEs in Japanese multidisciplinary pain centers. Methods. One hundred and forty-five patients suffering from the AEs were reviewed retrospectively and 105 patients of them were provided guidance on home exercise and activities of daily living based partially on a cognitive-behavioral approach. The intensity of pain was rated by the patients using a numerical rating scale (NRS). Furthermore, the Hospital Anxiety and Depression Scale (HADS) and the Pain Catastrophizing Scale (PCS) were used. Results. Eighty out of the 105 patients who received the guidance were followed up, 10 displayed a marked improvement, and 43 showed some improvement. Conclusions. Guidance on home exercise and activities of daily living based on a cognitive-behavioral approach alleviated the AEs that women suffered from after HPV vaccination in Japan.

A Single-Crystalline Mesoporous Quartz Superlattice.

There has been significant interest in the crystallization of nanostructured silica into α-quartz because of its physicochemical properties. We demonstrate a single-crystalline mesoporous quartz superlattice, a silica polymorph with unprecedentedly ordered hierarchical structures on both the several tens of nanometers scale and the atomic one. The mesoporous quartz superlattice consists of periodically arranged α-quartz nanospheres whose crystalline axes are mostly oriented in an assembly. The superlattice is prepared by thermal crystallization of amorphous silica nanospheres constituting a colloidal crystal. We found that the deposition of a strong flux of Li(+) only on the surface of silica nanospheres is effective for crystallization.

Usefulness of Mesoporous Silica as a Template for the Preparation of Bundles of Bi Nanowires with Precisely Controlled Diameter Below 10†nm.

The reduction of the diameter of Bi nanowires below 10 nm has been an important target because of the theoretical prediction with regard to significant enhancement in thermoelectric performance by size reduction. In this study, we have demonstrated the usefulness of mesoporous silica with tunable pore size as a template for the preparation of thin Bi nanowires with diameters below 10 nm. Bi was deposited within the templates through a liquid phase deposition using hexane and 1,1,3,3-tetramethyldisiloxane as a solvent and reducing agent, respectively. Bundles of thin Bi nanowires with non-crystalline frameworks were successfully obtained after the template removal. The diameter was precisely controlled between about 6 nm and 9 nm. The judicious choices of mesoporous silica and deposition conditions are critical for the successful preparation. The reliable formation of such thin Bi nanowires reported here opens up exciting new possibilities.

Preparation of Mesoporous Bimetallic Au-Pt with a Phase-Segregated Heterostructure Using Mesoporous Silica.

Mesoporous bimetallic Au-Pt with a phase-segregated heterostructure has been prepared by using mesoporous silica SBA-15 as a template. Au nanoparticles were prepared as a seed metal within the mesopores, and subsequently Pt was deposited, sandwiching the Au seeds. Energy-dispersive X-ray (EDX) spectral mapping showed that the framework of mesoporous bimetallic Au-Pt, prepared by removing the silica template with HF, was composed of Au nanoparticles joined with Pt nanowires. The Au/Pt ratio of the mesoporous bimetallic Au-Pt could be varied by controlling the number of Au deposition cycles. Pre-adsorbed CO (COad) stripping voltammetry of the mesoporous bimetallic Au-Pt showed that the surfaces of the joined bimetallic structure were electrochemically active. This could be attributed to the open framework structure having a high ratio of exposed bimetallic mesopore surfaces. The described preparative approach, involving a mesoporous silica template and stepwise deposition within the mesopores, enables control of the nanostructure of the bimetallic material, which is greatly promising for the further development of synthetic methodologies for bimetallic structures.

The Critical Effect of Niobium Doping on the Formation of Mesostructured TiO2 : Single-Crystalline Ordered Mesoporous Nb-TiO2 and Plate-like Nb-TiO2 with Ordered Mesoscale Dimples.

Highly ordered mesoporous niobium-doped TiO2 with a single-crystalline framework was prepared by using silica colloidal crystals with ca. 30 nm in diameter as templates. The preparation of colloidal crystals composed of uniform silica nanoparticles is a key to obtain highly ordered mesoporous Nb-doped TiO2 . The XPS measurements of Nb-doped TiO2 showed the presence of Nb(5+) and correspondingly Ti(3+) . With the increase in the amount of doped Nb, the crystalline phase of the product was converted from rutile into anatase, and the lattice spacings of both rutile and anatase phases increased. Surprisingly, the increase in the amount of Nb led to the formation of plate-like TiO2 with dimpled surfaces on one side, which was directly replicated from the surfaces of the colloidal silica crystals.

Preference for different anchor descriptors on visual analogue scales among Japanese patients with chronic pain.

CONTEXT: Although many previous studies have examined the preference of patients for different pain measurement scales, preference for anchor descriptors has not been thoroughly discussed. OBJECTIVES: To examine (1) the preferred end-phrases used in the VAS as anchor labels for Japanese patients with chronic pain, and (2) whether the preference differs according to factors such as age, sex, educational level, duration of pain, and pain intensity. METHODS: We performed an observational study in patients suffering from non-cancer chronic pain for more than 3 months at a pain center in Japan. The patients were asked to rate their pain intensity using four types of VAS that used the following different anchor descriptors: "worst pain" ("Worst"), "worst pain bearable" ("Bearable"), "worst pain imaginable" ("Imaginable"), and "worst pain you have ever experienced" ("Experienced"). They were also asked to rank the four scales according to ease of responding, and asked which descriptor best reflected their perceived pain. RESULTS: In total, 183 patients participated in the study. They consisted of 119 (65.0%) women and 64 (35.0%) men aged 18-84 years with the mean age of 56.9 years. "Experienced" was most preferred (69.8%), followed by "Bearable" (66.3%), "Worst" (48.8%), and "Imaginable" (16.9%). Factors such as age, sex, educational background, duration of pain, and pain intensity did not significantly affect the results. In 83.1% of patients, the preferred descriptor corresponded to the descriptor that best reflected patients' perceived pain. CONCLUSION: The frequently used expression "worst pain imaginable" is considered to be difficult to understand for most patients. Widely preferred descriptors, such as "worst pain you have ever experienced" and "worst pain bearable", should be used when evaluating perceived pain. The preference of anchor descriptors was not significantly affected by the factors such as age, sex, educational level, duration of pain, and pain intensity.

Survey on recognition of post-mastectomy pain syndrome by breast specialist physician and present status of treatment in Japan.

BACKGROUND: Post-mastectomy pain syndrome (PMPS) is chronic pain after breast cancer surgery and is reported to influence quality of life (QOL). Although the results of a survey in Japan showed high incidence, at 21-65 %, many of the patients had never been treated for PMPS. One reason for this low treatment rate may be poor understanding of PMPS by medical personnel. In this study, we conducted the survey by using questionnaire to assess current treatment and the recognitions of the medical personnel. METHODS: We mailed a questionnaire to 647 specialist members of the Breast Cancer Society. RESULTS: Of those, 34.7 % responsed. While PMPS was recognized by as much as 70.5 % of responding physicians, it was treated by as little as 47.7 % of the responders. In addition, while non-steroidal anti-inflammatory drugs (NSAIDs), which were ineffective in relieving PMPS, were used by 78.4 % of the responders, effective drugs were rarely used; therefore, treatment was considered ineffective by 69.5 %. This indicates that appropriate therapies are not widely used, and none of the current therapies are very effective. CONCLUSIONS: The results showed high recognition of PMPS pathology among physicians, but the treatment rate was as low as 47.7 %. NSAIDs were the main treatment, and the treatment effects were not satisfactory. It was revealed that currently appropriate treatment modalities have not been widely used. Education of physicians, distribution of treatment information and further studies are considered necessary for the spread of appropriate treatment modality.

Atherosclerosis induced by chronic inhibition of the synthesis of nitric oxide in moderately hypercholesterolaemic rabbits is suppressed by pitavastatin.

BACKGROUND AND PURPOSE: It is not clear if the new 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor pitavastatin prevents atherogenesis by a direct effect. Statins have a cholesterol-lowering effect, so an accessible animal model of atherosclerosis showing only moderate hypercholesterolaemia as in humans, is needed. The effects of pitavastatin were evaluated on atherosclerotic lesions accumulating foam cells derived from macrophages, produced in rabbits with moderate hypercholesterolaemia by chronic inhibition of nitric oxide synthase (NOS). EXPERIMENTAL APPROACH: White New Zealand rabbits were fed a 0.2% cholesterol diet with the NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) in the same diet. Pitavastatin (0.1 and 0.3 mg x kg(-1)) was given orally once a day for 8 weeks. The aortic arch and thoracic aorta were analysed by histochemistry and atherosclerotic lesions were quantified. The effect of pitavastatin on adhesion of THP-1 cells to endothelial cells, and cholesterol content in RAW264.7 cells incubated with oxidized or acetylated LDL were also investigated. KEY RESULTS: Atherosclerotic lesions containing foam cells were induced in a model of atherosclerosis in rabbits with moderate hypercholesterolaemia by chronic inhibition of NOS. The area of atherosclerotic lesions was diminished by pitavastatin administration. The adhesion of THP-1 cells and cholesteryl ester content in RAW macrophages were decreased by pitavastatin treatment. CONCLUSION: Atherosclerosis induced by chronic inhibition of NOS in moderately hypercholesterolaemic rabbits was suppressed by pitavastatin via inhibition of macrophage accumulation and macrophage foam cell formation.

[Effectiveness of oral tramadol hydrochloride for chronic non-malignant pain].

BACKGROUND: Tramadol hydrochloride is a centrally acting analgesic agent with two distinct mechanisms of action, a weak opioid agonist and an inhibitor of monoamine neurotransmitter reuptake, which produces significant analgesic effect synergistically. Though tramadol was approved in 1978 in Japan, it has rarely been used in clinical settings compared to foreign countries, e.g. Germany and USA. The aim of this study is to investigate effectiveness of oral tramadol for chronic non-malignant pain in Japan. METHODS: Tramadol was orally administered to patients with refractory non-malignant pain. Effects and adverse effects of tramadol were assessed about one month after the start of the administration. RESULTS: Out of 17 patients using tramadol daily, tramadol was found to be significantly effective in 4 patients (23.5%) and moderately effective in 8 patients (47.1%) from the viewpoint of pain relief as well as improvement of activities of daily livings. Side effects were reported by 7 patients (41.2%), which included nausea, constipation, and dizziness, but none of the side effects were serious. CONCLUSIONS: Tramadol is a useful option to treat non-malignant chronic pain, especially considering its very low abuse potential and a more acceptable side effect profile compared to non-steroidal anti-inflammatory drugs and opioids.

Local anesthetic cream prepared from lidocaine-tetracaine eutectic mixture.

Local anesthetic creams for the clinical treatment of conditions such as postherpetic neuralgia were prepared as an in-house formulation from the eutectic mixture of lidocaine-tetracaine (LT cream) using two eutectic mixtures of local anesthetic (EMLA) type bases. The LT formulation was compared with a lidocaine-prilocaine (LP cream) eutectic mixture formulated using the same base as EMLA. The chemical stability of lidocaine was examined in advance and was found to be stable for more than 3 months either in LT cream or in LP cream. The release rate of lidocaine from the formulated creams was examined using a cellulose ester membrane. The release rate of lidocaine from LT cream was similar to that from LP cream. The release rate of tetracaine was slightly slower than that of lidocaine in LT cream reflecting the larger molecular size of tetracaine. The penetration rate was examined in vitro using a Yucatan micropig skin. The penetration rate of lidocaine was similar between LT and LP creams. Infiltration anesthesia action examined in guinea pigs indicated that the difference between the two creams was statistically insignificant. The present study suggests the equivalence of the LT and LP creams as a local anesthetic and the potential of LT cream for clinical use either in the easy formulation or in the low-cost formulation.

[Effect of pitavastatin on macrophage cholesterol metabolism].

OBJECTIVES: Pitavastatin is the first totally synthetic HMG-Co A reductase inhibitor in Japan that significantly reduces LDL cholesterol while raising HDL cholesterol. Clinical trial showed that pitavastatin has potent effects for LDL cholesterol lowering and is expected effectively to prevent atherosclerosis. To clarify the mechanism of reduction of atherosclerosis by pitavastatin, we examined the effect of pitavastatin on foam cell formation of RAW264.7 macrophages. METHODS & RESULTS: Macrophages were cultured with pitavastatin for 24 h and exposed to oxidized LDL with pitavastatin for 3 days. Pitavastatin decreased the cellular cholesteryl ester content in a dose-dependent manner, and this effect was not via inhibition of HMG-CoA reductase because the 3-30 nM pitavastatin did not inhibit [14C]cholesterol synthesis from [14C]acetic acid and the effect was not influenced by addition of mevalonic acid. Pitavastatin increased neutral cholesterol esterase (NCEase) activity and did not affect ACAT activity, and decreased the expression of CD36 and ABCA1 mRNA. The mechanism of the increase of NCEase activity was that pitavastatin directly modified the substrate state, which was cholesterol oleate emulsified with lecithin. CONCLUSION: Clinical blood concentrations of pitavastatin prevent foam cell formation of RAW macrophages by oxidized LDL, and this was not via inhibition of HMG-CoA reductase, and modify substrate condition.

Influence of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on ubiquinone levels in rat skeletal muscle and heart: relationship to cytotoxicity and inhibitory activity for cholesterol synthesis in human skeletal muscle cells.

Although statins are prescribed as relatively safe and effective drugs for hypercholesterolemic patients, it has been reported that a significant side effect, myopathy, occurs infrequently during medication. Moreover, because statins decrease cardiac ubiquinone levels, the risk of cardiac dysfunction has been suggested. This study sought to evaluate and compare the cytotoxicity of statins (cerivastatin, pitavastatin, fluvastatin, simvastatin, atorvastatin and pravastatin) in cultured human skeletal muscle cells (HSkMCs) and the effects on ubiquinone levels in statin-treated rat skeletal muscle and heart. Cerivastatin, the most potent inhibitor of HMG-CoA reductase, showed the strongest cytotoxicity (over 10-fold) among the statins examined, while the effects of the others were in a similar range. In rat experiments, neither pitavastatin nor cerivastatin decreased ubiquinone levels in skeletal muscle, but both dose-dependently lowered ubiquinone levels in the heart. As the rates of reduction by pitavastatin (9.6% at 30 mg/kg) and cerivastatin (9.7% at 0.3 mg/kg) were almost equal, it was estimated that cerivastatin reduced ubiquinone levels in the rat heart approximately 100-fold more strongly than pitavastatin, based on the effective doses. We found that cerivastatin showed the most potent cytotoxicity in HSkMCs and strongly lowered ubiquinone levels in the rat heart.

Efficacy of interdisciplinary treatment for chronic nonmalignant pain patients in Japan.

OBJECTIVES: The implementation of interdisciplinary pain management is a relatively new concept in Japan. Although there are more than 4200 pain specialists in Japan at present, no multidisciplinary pain center has yet to be established. This prospective study is, to our knowledge, the first published evaluation of the effectiveness of multidisciplinary/interdisciplinary pain treatment in Japanese patients with chronic noncancer pain. METHODS: Ninety-nine patients with chronic noncancer pain were treated by an interdisciplinary approach in a Japanese outpatient pain clinic. Treatment was on the basis of the biopsychosocial model of pain and consisted of the following components: (1) education; (2) exercise and stretch; (3) long-term and short-term goal setting; (4) medication management; and (5) cognitive and behavioral techniques for problem solving and changing maladaptive behaviors. Each treatment session was 30 minutes and was held once every 1 to 3 weeks for 8 to 12 times according to the patients' progress and availability. The patients were assessed before and 2 to 4 weeks after the treatment. RESULTS: Results showed (1) 68.9% of patients reported a significant decrease in pain, (2) 92.0% stopped using inappropriate medication including nonsteroidal anti-inflammation drugs, benzodiazepines and muscle relaxants, (3) 51.4% underwent their usual daily activities without being disturbed by pain, and (4) 75.0% who had been unemployed because of pain returned to work. Overall, the treatment succeeded in 56.8% of the patients. CONCLUSIONS: Our results suggest that an interdisciplinary treatment based upon the biopsychosocial model of pain was associated with significant improvement in multiple outcomes in this sample of Japanese patients with chronic pain.