Voluntary Forelimbs Exercise Reduces Immobilization-Induced Mechanical Hyperalgesia in the Rat Hind Paw

Voluntary exercise is sufficient to protect against neuropathic pain. However, it is unclear whether voluntary exercise reduces immobilization-induced hyperalgesia. We examined the effect of voluntary forelimb exercise on immobilized-induced hyperalgesia in hind paws of rats. Wistar rats were randomly divided into the (1) both hind limbs immobilized group (IM group), (2) immobilization and exercise with nonimmobilized fore limbs group (EX group), and (3) control group. In the IM and EX groups, the bilateral ankle joints of each rat were immobilized in full plantar flexion with a plaster cast for eight weeks. In the EX group, voluntary exercise using nonimmobilized forelimbs in the running wheel was administered during the immobilization period, while hind limbs were kept immobilized (60 min/day, 5 days/week). Mechanical hyperalgesia in the hind paw was measured using a digital von Frey device every week. To investigate the abnormality of primary sensory neurons and central sensitization, the number of calcitonin gene-related peptide-positive cells in the dorsal root ganglion and the expression level of calcitonin gene-related peptide in the spinal dorsal horn were analyzed by immunohistochemical staining. Immobilization-induced mechanical hyperalgesia was inhibited in the EX group compared to the IM group at three weeks after immobilization. In the EX group, the number of calcitonin gene-related peptide-positive cells in the dorsal root ganglion and the expression level of calcitonin gene-related peptide were significantly decreased compared to those in the IM group. Our results therefore suggest that voluntary forelimb exercise during hind limb immobilization partially reduces immobilization-induced hyperalgesia by suppressing that the plastic changes of the primary sensory nerves that excessively transmit pain and increased responsiveness of nociceptive neurons in the spinal dorsal horn

Factors Affecting Persistent Postoperative Pain in Patients with Hip Fractures

Osteoporotic fractures are common among older people, and hip fractures (HF) can be devastating. Surgery is indicated for most cases of HF, and chronic persistent postoperative pain is likely to occur. This study investigated the multifaceted factors related to persistent pain occurring during the acute phase and subacute phase of recovery after HF surgery. We conducted a prospective 8-week study of older HF patients after surgery. We evaluated pain intensity, depression symptoms, the fear of falling, pain catastrophizing, cognition and attention, the ability to perform activities of daily living, and the physical performance at 2 weeks (acute phase) and at 4 weeks (subacute phase) after surgery. Patients were divided into the light group (Verbal Rating Scale (VRS) score ?1) and severe group (VRS score ?2) according to pain intensity at 8 weeks (recovery phase) after surgery. Factors affecting persistent postoperative pain during recovery were examined using logistic regression analysis. Seventy-two patients were analyzed: 50 in the light group and 22 in the severe group. In the severe group, pain with movement and Pain Catastrophizing Scale scores were higher than those of the light group at 2 weeks and at 4 weeks after surgery. The regression analysis showed that pain with movement at 2 weeks and at 4 weeks after surgery and pain catastrophizing at 4 weeks after surgery were related to persistent postoperative pain. HF patients may have persistent pain if they continue to experience pain and catastrophize their pain during the acute phase and subacute phase after surgery

Effects of a Rehabilitation Program Combined with Pain Management That Targets Pain Perception and Activity Avoidance in Older Patients with Acute Vertebral Compression Fracture: a Randomised Controlled Trial

This study aimed to investigate the efect of a rehabilitation program combined with pain management targeting pain perception and activity avoidance on multifaceted outcomes in older patients with acute vertebral compression fractures (VCFs). We randomised 65 older adults with acute VCFs to either an intervention group (n = 32), involving usual rehabilitation combined with pain management that targeted pain perception and activity avoidance, or a control group (n = 33), involving only usual rehabilitation. Te usual rehabilitation was initiated immediately after admission. All patients were treated conservatively. Pain management aimed to improve the patients’ daily behaviour by increasing their daily activities despite pain, rather than by focusing on eliminating the pain. Pain intensity and psychological statuses such as depression, pain catastrophising, and physical activity levels were assessed on admission. Two weeks postadmission and at discharge, physical performance measures were assessed along with the above-given measurements. A signifcant main efect of the group was observed for the intensity of lower back pain, favouring the intervention group (F = 5.135, p = 0.027). At discharge, it was signifcantly better in the intervention group than in the control group (p = 0.011). A time-by-group interaction emerged for magnifcation of the pain catastrophising scale (p = 0.012), physical activity levels (p < 0.001), and six-minute walking distance (p = 0.006), all favouring the intervention group. Rehabilitation programs combined with pain management targeting pain perception and activity avoidance could be an efective conservative treatment for older patients with acute VCFs

Effect of exercise and/or educational interventions on physical activity and pain in patients with hip/knee osteoarthritis: A systematic review with meta-analysis

Objective: To investigate the effectiveness of exercise and/or educational intervention on physical activity and pain in patients with hip/knee osteoarthritis (OA) using systematic review and meta-analysis.Methods: We searched randomized controlled trials that investigated physical activity and pain and compared exercise and/or educational intervention with usual care in patients with hip/knee OA in MEDLINE (PubMed), ProQuest, Scopus, and the Physiotherapy Evidence Database (PEDro), including all those published by April 30, 2022 and written in English. Studies that newly applied analgesics after onset of the intervention were excluded. The revised Cochrane risk-of-bias tool for randomized trials was used to assess the methodological qualities. The random-effects model was used for meta-analysis with standard mean differences using RevMan version 5.4. The body of evidence for each study was synthesized using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.Results: Twenty studies including 2,350 patients were included (7 exercise studies, 8 educational intervention studies and 5 combination studies). The meta-analysis demonstrated that there is very low evidence that combination therapy of exercise and educational intervention improve the physical activity level at the endpoint (4 articles; SMD 0.33, 95% CI 0.04 to 0.51, P = 0.03). Low evidence was observed for combination therapy reducing pain (4 articles; SMD -0.15, 95% CI -0.29 to -0.02, P = 0.03).Discussion: The current evidence indicated that combination therapy of exercise and educational intervention leads to improved physical activity and pain reduction in hip/knee OA patients, but the risk of bias in each study, especially in allocation concealment, downgraded the evidence level. These findings support the use of a combination therapy of exercise and educational intervention to promote physical activity levels in patients with hip/knee OA.Trail registration: There was no financial support for this research. The protocol was registered at the International Prospective Register of Systematic Reviews (registration code: CRD42020205804)

地震発生帯における深部掘削孔を用いた長期計測

Large earthquakes occur frequently in subduction zones. Most earthquakes are generated in the seismogenic zone, a fairly limited area confined to the shallower regions of the subduction plate boundary. To understand the processes of earthquake generation, it is essential to monitor the physical and mechanical properties of the seismogenic zone over long periods. At present, there are no deep borehole observations of the seismogenic zone more than 3km below seafloor, because it has, until now, been impossible to penetrate to such depths below the sea floor. The Integrated Ocean Drilling Program (IODP), scheduled to begin in 2003, plans to drill boreholes beneath the ocean floor using a multiple-drilling platform operation. The IODP riser-quipped drilling ship (Chikyu) enables the emplacement of boreholes up to 0km beneath the ocean floor, and will provide opportunities to conduct long-term deep borehole observations in the seismogenic zone. Long-term borehole observations in the seismogenic zone are expected to require the development of advanced sampling, monitoring, and recording technology. Here, we discuss the scientific objectives, engineering and technical challenges, and experimental design for a deep borehole, long-term deepborehole monitoring system aimed at understanding the processes of earthquake generation in the seismogenic zone of subduction plate boundaries. We focus specifically on the relationships between environmental conditions in the deep subsurface, details of monitoring and recording, and design and implementation of scientific tools and programs

Voluntary Forelimbs Exercise Reduces Immobilization-Induced Mechanical Hyperalgesia in the Rat Hind Paw

Voluntary exercise is sufficient to protect against neuropathic pain. However, it is unclear whether voluntary exercise reduces immobilization-induced hyperalgesia. We examined the effect of voluntary forelimb exercise on immobilized-induced hyperalgesia in hind paws of rats. Wistar rats were randomly divided into the (1) both hind limbs immobilized group (IM group), (2) immobilization and exercise with nonimmobilized fore limbs group (EX group), and (3) control group. In the IM and EX groups, the bilateral ankle joints of each rat were immobilized in full plantar flexion with a plaster cast for eight weeks. In the EX group, voluntary exercise using nonimmobilized forelimbs in the running wheel was administered during the immobilization period, while hind limbs were kept immobilized (60 min/day, 5 days/week). Mechanical hyperalgesia in the hind paw was measured using a digital von Frey device every week. To investigate the abnormality of primary sensory neurons and central sensitization, the number of calcitonin gene-related peptide-positive cells in the dorsal root ganglion and the expression level of calcitonin gene-related peptide in the spinal dorsal horn were analyzed by immunohistochemical staining. Immobilization-induced mechanical hyperalgesia was inhibited in the EX group compared to the IM group at three weeks after immobilization. In the EX group, the number of calcitonin gene-related peptide-positive cells in the dorsal root ganglion and the expression level of calcitonin gene-related peptide were significantly decreased compared to those in the IM group. Our results therefore suggest that voluntary forelimb exercise during hind limb immobilization partially reduces immobilization-induced hyperalgesia by suppressing that the plastic changes of the primary sensory nerves that excessively transmit pain and increased responsiveness of nociceptive neurons in the spinal dorsal horn

A major isoform of mitochondrial trans-2-enoyl-CoA reductase is dispensable for wax ester production in Euglena gracilis under anaerobic conditions.

Under anaerobic conditions, Euglena gracilis produces a large amount of wax ester through mitochondrial fatty acid synthesis from storage polysaccharides termed paramylon, to generate ATP. Trans-2-enoyl-CoA reductases (TERs) in mitochondria have been considered to play a key role in this process, because the enzymes catalyze the reduction of short chain length CoA-substrates (such as crotonyl-CoA). A TER enzyme (EgTER1) has been previously identified and enzymologically characterized; however, its physiological significance remained to be evaluated by genetic analysis. We herein generated EgTER1-knockdown Euglena cells, in which total crotonyl-CoA reductase activity was decreased to 10% of control value. Notably, the knockdown cells showed a severe bleaching phenotype with deficiencies in chlorophylls and glycolipids, but grew normally under heterotrophic conditions (with glucose supplementation). Moreover, the knockdown cells accumulated much greater quantities of wax ester than control cells before and after transfer to anaerobic conditions, which was accompanied by a large metabolomic change. Furthermore, we failed to find any contribution of other potential TER genes in wax ester production. Our findings propose a novel role of EgTER1 in the greening process and demonstrate that this enzyme is dispensable for wax ester production under anaerobic conditions

The Consumption of Bicarbonate-Rich Mineral Water Improves Glycemic Control

Hot spring water and natural mineral water have been therapeutically used to prevent or improve various diseases. Specifically, consumption of bicarbonate-rich mineral water (BMW) has been reported to prevent or improve type 2 diabetes (T2D) in humans. However, the molecular mechanisms of the beneficial effects behind mineral water consumption remain unclear. To elucidate the molecular level effects of BMW consumption on glycemic control, blood metabolome analysis and fecal microbiome analysis were applied to the BMW consumption test. During the study, 19 healthy volunteers drank 500 mL of commercially available tap water (TW) or BMW daily. TW consumption periods and BMW consumption periods lasted for a week each and this cycle was repeated twice. Biochemical tests indicated that serum glycoalbumin levels, one of the indexes of glycemic controls, decreased significantly after BMW consumption. Metabolome analysis of blood samples revealed that 19 metabolites including glycolysis-related metabolites and 3 amino acids were significantly different between TW and BMW consumption periods. Additionally, microbiome analysis demonstrated that composition of lean-inducible bacteria was increased after BMW consumption. Our results suggested that consumption of BMW has the possible potential to prevent and/or improve T2D through the alterations of host metabolism and gut microbiota composition