Effects of Isometric Quadriceps Muscle Exercise with Visual and Auditory Feedback at 1 Year after Total Knee Arthroplasty.

OBJECTIVE: To examine the effect of isometric quadriceps exercises with visual and auditory feedback after total knee arthroplasty (TKA). METHODS: The sample included 41 patients from our previous study who could be followed up for 1 year after TKA. Patients in the intervention group performed isometric quadriceps exercises with visual and auditory feedback using the quadriceps training machine from the 2nd to the 14th day after TKA, whereas those in the control group underwent standard postoperative rehabilitation (without visual or auditory feedback during isometric quadriceps exercises) in the hospital. Patients were evaluated for pain intensity, timed up and go test (TUG) score, 10-m gait speed, 6-minute walking distance (6MWD), and the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) score 1 year after TKA. Additionally, exercise habits and responses to the International Physical Activity Questionnaire (IPAQ) were investigated. RESULTS: Pain intensity was significantly lower in the intervention group than in the control group. Greater improvements in the TUG test scores, 10-m gait speed, 6MWD, and WOMAC scores were observed in the intervention group. Walking activity, as recorded by the IPAQ, and the proportion of patients with exercise habits were significantly higher in the intervention group than in the control group. CONCLUSIONS: These results suggest that performing isometric quadriceps exercise with visual and auditory feedback using the quadriceps training machine has good effects, such as pain reduction, physical function improvement, exercise tolerance, and increased physical activity at 1 year after TKA.

Mechanical Stress Via Muscle Contractile Exercise Suppresses Atrophic Alterations of Bone-microstructure in Immobilized Rat Femurs.

OBJECTIVES: This study aimed to determine whether mechanical stress via muscle contractile exercise with belt electrode-skeletal muscle electrical stimulation (B-SES) device effectively prevents immobilization-induced bone atrophy. METHODS: Wistar rats were randomly divided into the control (CON) group, immobilization (IM) group (immobilized treatment only), HES and LES groups (immobilized treatment and high or low-intensity electrical muscular stimulation through B-SES device). Bilateral femurs were used for X-ray micro-CT and biomechanical tests. RESULTS: The maximum load value was significantly lower in the IM and HES groups than in the CON group and significantly higher in the LES group than in the IM group. The maximum crushing load was significantly lower in the IM, HES, and LES groups than in the CON group, and significantly higher in the HES and LES groups than that in the IM group. In micro-CT, the mechanical stress by B-SES device did not affect degenerative microstructural changes in the cortical bone, but prevented those changes in the cancellous bone. CONCLUSIONS: Applying mechanical stress via B-SES device suppressed the loss of cancellous bone density and degenerative microstructural changes caused by immobilization, which in turn suppressed the reduction of bone strength. From these findings, muscle contractile exercise may be effective in preventing immobilization-induced bone atrophy.

Low-intensity pulsed ultrasound phonophoresis with diclofenac alleviated inflammation and pain via downregulation of M1 macrophages in rats with carrageenan-induced knee joint arthritis.

Objective: This study aimed to investigate the effects of low-intensity pulsed ultrasound (LIPUS) phonophoresis with diclofenac on inflammation and pain in the acute phase of carrageenan-induced arthritis in rats. Design: 60 male Wistar rats were randomly divided into the arthritis, diclofenac, LIPUS, phonophoresis, and sham-arthritis control groups. LIPUS and transdermal diclofenac gel were applied to the lateral side of the inflamed knee for 7 days, initiated postinjection day 1. In the phonophoresis group, diclofenac gel was rubbed onto the skin, followed by LIPUS application over the medication. Knee joint transverse diameters, pressure pain thresholds (PPTs), and paw withdrawal thresholds (PWT) were evaluated. The number of CD68-, CD11c-, and CD206-positive cells, and IL-1ß and COX-2 mRNA expression were analyzed 8 days after injection. Results: In the phonophoresis group, the transverse diameter, PPT, PWT significantly recovered at the day 8 compared to those in the LIPUS and diclofenac groups. The number of CD68- and CD11c-positive cells in the phonophoresis group was significantly lower than that in the LIPUS and diclofenac groups, but no significant differences were observed among three groups in CD206-positive cells. IL-1ß and COX-2 mRNA levels were lower in the phonophoresis group than in the arthritis group, although there were no differences among the LIPUS, diclofenac, and phonophoresis groups. Conclusion: LIPUS phonophoresis with diclofenac is more effective to ameliorate inflammation and pain compared to diclofenac or LIPUS alone, and the mechanism involves the decrease of M1 macrophages.

Regular walking exercise prior to knee osteoarthritis reduces joint pain in an animal model.

We investigated the effect of regular walking exercise prior to knee osteoarthritis (OA) on pain and synovitis in a rat monoiodoacetic acid (MIA)-induced knee OA model. Seventy-one male Wistar rats were divided into three groups: (i) Sedentary + OA, (ii) Exercise + OA, and (iii) Sedentary + Sham groups. The Exercise + OA group underwent a regular treadmill walking exercise at 10 m/min (60 min/day, 5 days/week) for 6 weeks, followed by a 2-mg MIA injection in the right knee. The right knee joint was removed from rats in this group at the end of the 6-week exercise period and at 1 and 6 weeks after the MIA injection. After the 6 weeks of treadmill exercise but before MIA injection, there were no significant differences among the three groups in the pressure pain threshold, whereas at 1 week post-injection, the Exercise + OA group's pressure pain threshold was significantly higher than that in the Sedentary + OA group, and this difference persisted until the end of the experimental period. The histological changes in articular cartilage and subchondral bone revealed by toluidine blue staining showed no difference between the Sedentary + OA and EX + OA groups. The expression levels of interleukin (IL)-4 and IL-10 mRNA in the infrapatellar fat pad and synovium were significantly increased by the treadmill exercise. Significant reductions in the number of CD68-, CD11c-positive cells and IL-1ß mRNA expression and an increase in the number of CD206-positive cells were observed at 1 week after the MIA injection in the Exercise + OA group compared to the Sedentary + OA group. These results suggest that regular walking exercise prior to the development of OA could alleviate joint pain through increases in the expressions of anti-inflammatory cytokines in the rat infrapatellar fat pad and synovium.

A case of complete resection of prostate stromal sarcoma after neoadjuvant chemotherapy.

Introduction: Prostatic stromal sarcoma is an extremely rare malignancy of the prostate with a poor prognosis. Case presentation: A 65-year-old man presented with dyschezia, and computed tomography showed a large prostate mass. The diagnosis was prostate stromal sarcoma by transrectal needle biopsy. Magnetic resonance imaging suggested rectal infiltration. The patient underwent 4 courses of neoadjuvant chemotherapy with gemcitabine and docetaxel hydrate followed by total pelvic exenteration. Conclusion: No recurrence has occurred at 5 years after the surgery. This is the first report of complete resection in prostate stromal sarcoma after neoadjuvant chemotherapy with gemcitabine and docetaxel hydrate.

The Relationship Between Physical Activity and Limited Range of Motion in the Older Bedridden Patients.

Background: The purpose of this study is to examine the association between physical activity and contracture in older patients confined to bed in long-term care (LTC) facilities. Methods: Patients wore ActiGraph GT3X+ for 8 hours on their wrists, and vector magnitude (VM) counts were obtained as the amount of activity. The passive range of motion (ROM) of joints was measured. The severity of ROM restriction classified, as the tertile value of the reference ROM of each joint, was scored 1-3 points. Spearman's rank correlation coefficients (Rs) were used to measure the association between the VM counts per day and ROM restrictions. Results: The sample comprised 128 patients with a mean (SD) age of 84.8 (8.8) years. The mean (SD) of VM was 84574.6 (115195.2) per day. ROM restriction was observed in most joints and movement directions. ROMs in all joints and movement directions, except wrist flexion and hip abduction, were significantly correlated with VM. Furthermore, the VM and ROM severity scores showed a significant negative correlation (Rs = -0.582, p < .0001). Conclusions: A significant correlation between the physical activity and ROM restrictions indicates that a decrease in the amount of physical activity could be one of the causes of contracture.

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 effect 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. The 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 significant main effect 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 significantly better in the intervention group than in the control group (p = 0.011). A time-by-group interaction emerged for magnification 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 effective conservative treatment for older patients with acute VCFs.

Effects of low-level laser therapy on inflammatory symptoms in an arthritis rat model.

[Purpose] This study evaluated the effect of low-level laser therapy on inflammatory signs in an arthritis rat model as a foundation for elucidating the mechanism of the anti-inflammatory effect. [Materials and Methods] Eigteen Wistar rats were divided into three groups: group I (arthritis without low-level laser therapy), group II (arthritis with low-level laser therapy), and the control group (sham arthritis control). Arthritis was induced in the right knee by injecting a mixture of kaolin and carrageenan. Low-level laser therapy was continued for seven days after the onset of arthritis by 60 times of repeated irradiation for 10 seconds in the right knee joint area. The joint transverse diameter, pressure pain threshold in the affected knee joint, and mechanical paw withdrawal threshold at the distant site were evaluated the day before the injection and one, three, and seven days after the injection. Pathological changes were observed. [Results] Group II showed better improvement in swelling and pain in the affected knee joint and secondary hyperalgesia at the distance site when compared to group I. In group II, there was only mild infiltration of synovial cells, and the progression of arthritis was suppressed compared with that of group I. [Conclusion] Low-level laser therapy can mitigate swelling and inflammatory pain in the affected knee joint and prevent secondary hyperalgesia.

Progression of microstructural deterioration in load-bearing immobilization osteopenia.

PURPOSE: Immobilization osteopenia is a major healthcare problem in clinical and social medicine. However, the mechanisms underlying this bone pathology caused by immobilization under load-bearing conditions are not yet fully understood. This study aimed to evaluate sequential changes to the three-dimensional microstructure of bone in load-bearing immobilization osteopenia using a fixed-limb rat model. MATERIALS AND METHOD: Eight-week-old specific-pathogen-free male Wistar rats were divided into an immobilized group and a control group (n = 60 each). Hind limbs in the immobilized group were fixed using orthopedic casts with fixation periods of 1, 2, 4, 8, and 12 weeks. Feeding and weight-bearing were freely permitted. Length of the right femur was measured after each fixation period and bone microstructure was analyzed by micro-computed tomography. The architectural parameters of cortical and cancellous bone were analyzed statistically. RESULTS: Femoral length was significantly shorter in the immobilized group than in the control group after 2 weeks. Total area and marrow area were significantly lower in the immobilized group than in the control group from 1 to 12 weeks. Cortical bone area, cortical thickness, and polar moment of inertia decreased significantly after 2 weeks. Some cancellous bone parameters showed osteoporotic changes at 2 weeks after immobilization and the gap with the control group widened as the fixation period extended (P < 0.05). CONCLUSION: The present results indicate that load-bearing immobilization triggers early deterioration of microstructure in both cortical and cancellous bone after 2 weeks.

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).

Muscle contractile exercise through a belt electrode device prevents myofiber atrophy, muscle contracture, and muscular pain in immobilized rat gastrocnemius muscle.

PURPOSE: Immobilization of skeletal muscles causes muscle atrophy, muscle contracture, and muscle pain, the mechanisms of which are related to macrophage accumulation. However, muscle contractile exercise through a belt electrode device may mitigate macrophage accumulation. We hypothesized that such exercise would be effective in preventing myofiber atrophy, muscle contracture, and muscular pain. This study tested this hypothesis in immobilized rat gastrocnemius muscle. MATERIALS AND METHODS: A total of 32 rats were divided into the following control and experimental groups: immobilization (immobilized treatment only), low-frequency (LF; immobilized treatment and muscle contractile exercise with a 2 s (do) /6 s (rest) duty cycle), and high-frequency (HF; immobilized treatment and muscle contractile exercise with a 2 s (do)/2 s (rest) duty cycle). Electrical stimulation was performed at 50 Hz and 4.7 mA, and muscle contractile exercise was applied to the lower limb muscles for 15 or 20 min/session (once daily) for 2 weeks (6 times/week). After the behavioral tests, the bilateral gastrocnemius muscles were collected for analysis. RESULTS: The number of macrophages, the Atrogin-1 and MuRF-1 mRNA expression, and the hydroxyproline content in the HF group were lower than those in the immobilization and LF groups. The cross-sectional area (CSA) of type IIb myofibers in the superficial region, the PGC-1α mRNA expression, and the range of motion of dorsiflexion in the HF group were significantly higher than those in the immobilization and LF groups. The pressure pain thresholds in the LF and HF groups were significantly higher than that in the immobilization group, and the nerve growth factor (NGF) content in the LF and HF groups was significantly lower than that in the immobilization group. CONCLUSION: Muscle contractile exercise through the belt electrode device may be effective in preventing immobilization-induced myofiber atrophy, muscle contracture, and muscular pain in the immobilized rat gastrocnemius muscle.

Differential diagnosis and prognosis of small renal masses: association with collateral vessels detected using contrast-enhanced computed tomography.

BACKGROUND: Active surveillance (AS) is one of the treatment methods for patients with small renal masses (SRMs; < 4 cm), including renal cell carcinomas (RCCs). However, some small RCCs may exhibit aggressive neoplastic behaviors and metastasize. Little is known about imaging biomarkers capable of identifying potentially aggressive small RCCs. Contrast-enhanced computed tomography (CECT) often detects collateral vessels arising from neoplastic angiogenesis in RCCs. Therefore, this study aimed to evaluate the association between SRM differential diagnoses and prognoses, and the detection of collateral vessels using CECT. METHODS: A total of 130 consecutive patients with pathologically confirmed non-metastatic SRMs (fat-poor angiomyolipomas [fpAMLs; n = 7] and RCCs [n = 123]) were retrospectively enrolled. Between 2011 and 2019, SRM diagnoses in these patients were confirmed after biopsy or surgical resection. All RCCs were surgically resected. Regardless of diameter, a collateral vessel (CV) was defined as any blood vessel connecting the tumor from around the kidney using CECT. First, we analyzed the role of CV-detection in differentiating between fpAML and RCC. Then, we evaluated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of RCC diagnosis based on CV-detection using CECT. We also assessed the prognostic value of CV-detection using the Fisher exact test, and Kaplan-Meier method and the log-rank test. RESULTS: The sensitivity, specificity, PPV, NPV, and accuracy of CV-detection for the diagnosis of small RCCs was 48.5, 45.5, 100, 100, and 9.5% respectively. Five of 123 (4.1%) patients with RCC experienced recurrence. CV-detection using CECT was the only significant factor associated with recurrence (p = 0.0177). Recurrence-free survival (RFS) was significantly lower in patients with CV compared with in those without CV (5-year RFS 92.4% versus 100%, respectively; p = 0.005). In addition, critical review of the CT images revealed the CVs to be continuous with the venous vessels around the kidney. CONCLUSIONS: The detection of CVs using CECT is useful for differentiating between small fpAMLs and RCCs. CV-detection may also be applied as a predictive parameter for small RCCs prone to recurrence after surgical resection. Moreover, AS could be suitable for small RCCs without CVs.

Relationship Between Muscle Quality or Stiffness Measured by Ultrasonography and Range of Motion in Hospitalized Older Adults.

Older adults who require nursing care have joint contractures characterized by limited range of motion (ROM). The present study investigated age-related muscle changes using ultrasonography and the relationship between ROM and muscle changes in older adults. Twenty-two healthy young adults (mean age: 23.3 y) and 60 hospitalized older adults (mean age: 86.1 y) participated. ROM of hip abduction was measured using a goniometer. Echo intensity (EI), reflecting interstitial fibrous tissue or fat within adductor longus (ADDl) was measured using B-mode ultrasonography, and strain ratio (SR), reflecting ADDl stiffness, was measured by strain elastography. The Mann-Whitney U-test and Spearman's correlation test were used for analysis. The ROM and SR of older adults were significantly lower than those of young adults (both p values <0.001). The EI was significantly higher in older adults than in young adults (p < 0.001). In older adults, the SR was moderately correlated with ROM (ρ = 0.49, p < 0.001). In conclusion, limited ROM and increase in interstitial fibrous tissue or fat and stiffness occur with aging, and the SR measured by strain elastography is useful for investigating the effect of muscle stiffness on the ROM of hospitalized older adults.

Relationship among trunk control, activities of daily living, and upper extremity function during the first week after stroke in patients with acute cerebral infarction.

[Purpose] We aimed to identify the relationship among trunk control, activities of daily living, and upper extremity function during the first week after stroke in patients with acute cerebral infarction. [Participants and Methods] Ninety-five patients with first cerebral infarction were included. Trunk control was assessed using the Postural Assessment Scale for Stroke. Additionally, activities of daily living were evaluated using the Functional Independence Measure, and upper extremity function was assessed using the upper extremity component of the Fugl-Meyer Assessment. Correlation analysis was performed to examine the relationships among these three measures. Furthermore, stepwise multiple regression analysis was performed to investigate the factors affecting activities of daily living. [Results] The total score and two subcategories of the Postural Assessment Scale for Stroke were significantly correlated with the Functional Independence Measure motor values. Stepwise multiple regression analysis revealed age and the Postural Assessment Scale for Stroke as factors influencing the Functional Independence Measure. Moreover, the Postural Assessment Scale for Stroke and upper extremity component of Fugl-Meyer Assessment showed a high correlation. [Conclusion] The trunk control ability assessed using the Postural Assessment Scale for Stroke is strongly correlated with activities of daily living estimated using the Functional Independence Measure in the first week after stroke in patients with acute cerebral infarction. The upper extremity component of Fugl-Meyer Assessment was not identified as a factor affecting the Functional Independence Measure.

Depression, catastrophizing, and poor performance in women with persistent acute low back pain from vertebral compression fractures: A prospective study.

BACKGROUND: Research on the multi-faceted characteristics of persistent severe acute lower back pain (LBP) resulting from acute vertebral compression fractures (VCFs) is lacking. OBJECTIVE: To investigate the psychological and functional status of older patients with persistent severe acute LBP after conservative treatment of VCFs. METHODS: This prospective study included women aged 50 years and older who had acute VCFs and were admitted to the hospital. Pain intensity, depression, pain catastrophizing, activities of daily living (ADL), muscle strength, and vertebral deformity were assessed on admission. At 2 and 4 weeks post-admission, physical performance tests were performed along with the above measures. RESULTS: We divided 131 participants into severe (n= 64) and mild (n= 67) groups according to their pain intensity at 4 weeks. Compared to the mild group, the severe group showed significantly higher levels of depression and catastrophizing, with significantly poorer muscle strength and endurance. There were no significant differences in ADL and vertebral deformities between the two groups. CONCLUSIONS: Our results suggest that older patients with persistent severe acute LBP resulting from VCFs tend to be depressed and pain catastrophizing. Furthermore, persistent severe acute LBP negatively impacts endurance and muscle strength but not ADL.

Short-Term Effects of Isometric Quadriceps Muscle Exercise with Auditory and Visual Feedback on Pain, Physical Function, and Performance after Total Knee Arthroplasty: A Randomized Controlled Trial.

Severe acute pain after total knee arthroplasty (TKA) may cause delay in muscle strength and functional recovery, and it is a risk factor for chronic postoperative pain. Although pharmacological approaches are the typical firstline to treat acute pain; recently, nonpharmacological approaches such as exercise have been increasingly applied. The purpose of this investigation was to evaluate the effects of a rehabilitation program involving isometric quadriceps exercise with auditory and visual feedback to improve the short-term outcome after TKA. Sixty-two patients, planning a primary unilateral TKA, were randomly assigned to either an intervention group (n = 31) involving isometric quadriceps exercise with auditory and visual feedback in usual rehabilitation after TKA or a control group (n = 31) involving a standardized program for TKA. Patients in the intervention group performed the isometric quadriceps muscle exercise using the Quadriceps Training Machine from 2 to 14 days after TKA instead of the traditional quadriceps sets. Pain intensity, isometric knee extension strength, range of motion, timed up and go test (TUG), 10-m gait speed, 6-minute walking distance, the Western Ontario and McMaster University Osteoarthritis index (WOMAC), the hospital anxiety and depression scale, and the pain catastrophizing scale were assessed before TKA (baseline) and 1 to 3 weeks after TKA. Pain intensity significantly decreased in the intervention group than in the control group at 1 (p = 0.005), 2 (p = 0.002), and 3 (p = 0.010) weeks after TKA. Greater improvements in TUG (p = 0.036), 10-m gait speed (p = 0.047), WOMAC total score (p = 0.017), pain (p = 0.010), and function (p = 0.028) 3 weeks after TKA were observed in the intervention group. These results suggest that isometric quadriceps exercises with auditory and visual feedback provided early knee pain relief, possibly leading to better improvements in physical performance, and patient's perception of physical function in the early stages of postoperative TKA. Further studies should investigate whether this short-term effect is sustainable.

Myonuclear apoptosis via cleaved caspase-3 upregulation is related to macrophage accumulation underlying immobilization-induced muscle fibrosis.

INTRODUCTION/AIMS: Although macrophage accumulation plays a key role in the development of immobilization-induced muscle fibrosis, the underlying mechanisms remain unclear. Therefore, we focused on the alterations of myonuclear apoptosis via cleaved caspase-3, and investigated whether these changes may be related to macrophage accumulation. METHODS: Eight-week-old Wistar rats were divided into immobilization and control groups, and the soleus muscles were selected for analysis. RESULTS: The mRNA and protein expression of collagen and the number of CD11b-positive cells were significantly higher in the immobilized rats than in the control rats at 1 and 2 weeks. TdT-mediated dUTP nick end-labeling (TUNEL)-positive myonuclei counts in 1- and 2-week control rats were 0.2 ± 0.1 and 0.2 ± 0.5, whereas they were 1.0 ± 0.6 and 1.1 ± 0.5 in 1- and 2-week immobilized rats. The cleaved caspase-3 protein expressions in 1- and 2-week control rats were 0.2 ± 0.1 and 0.2 ± 0.1, whereas they were 0.5 ± 0.1 and 0.4 ± 0.2 in 1- and 2-week immobilized rats. TUNEL-positive myonuclei counts and cleaved caspase-3 protein expression were significantly higher in immobilized rats than in control rats at 1 and 2 weeks. The numbers of myonuclei in 1- and 2-week control rats were 2.8 ± 0.1 and 2.6 ± 0.4, whereas they were 2.2 ± 0.4 and 2.2 ± 0.2 in 1- and 2-week immobilized rats. The numbers of myonuclei were significantly lower in immobilized than in control rats at both time-points. DISCUSSION: Myonuclear apoptosis via the upregulation of cleaved caspase-3 might induce macrophage accumulation. These alterations are related to immobilization-induced muscle fibrosis.

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.

Effect of belt electrode-skeletal muscle electrical stimulation on immobilization-induced muscle fibrosis.

PURPOSE: Macrophage accumulation in response to decreasing myonuclei may be the major mechanism underlying immobilization-induced muscle fibrosis in muscle contracture, an intervention strategy suppressing these lesions is necessary. Therefore, this research investigated the effect of belt electrode-skeletal muscle electrical stimulation (B-SES), a new electrical stimulation device, to the macrophage accumulation via myonuclei decrease in immobilization-induced muscle fibrosis. MATERIALS AND METHODS: 18 Wistar male rats were divided into the control group, immobilization group (with plaster cast fixation to immobilize the soleus muscles in a shortened position for 2 weeks), and B-SES group (with muscle contractile exercise through B-SES during the immobilization period). B-SES stimulation was performed at a frequency of 50 Hz and an intensity of 4.7 mA, muscle contractile exercise by B-SES was applied to the lower limb muscles for 20 minutes/session (twice a day) for 2 weeks (6 times/week). The bilateral soleus muscles were used for histological, immunohistochemical, biochemical, and molecular biological analyses. RESULTS: The number of myonuclei was significantly higher in the B-SES group than in the immobilization group, and there was no significant difference between the B-SES and control groups. The cross-sectional area of type I and II myofibers in the immobilization and B-SES groups was significantly lower than that in the control group, and the cross-sectional area of type I myofibers in the B-SES group was higher than that in the immobilization group. However, Atrogin-1 and MuRF-1 mRNA expression in the immobilization and B-SES groups was significantly higher than those in the control group. Additionally, the number of macrophages, IL-1ß, TGF-ß1, and α-SMA mRNA expression, and hydroxyproline expression was significantly lower in the control and B-SES groups than those in the immobilization group. CONCLUSION: This research surmised that muscle contractile exercise through B-SES prevented immobilization-induced muscle fibrosis, and this alteration suppressed the development of muscle contracture.

Effects of Cryotherapy Applied at Different Temperatures on Inflammatory Pain During the Acute Phase of Arthritis in Rats.

OBJECTIVE: The biological mechanisms of cryotherapy for managing acute pain remain unclear. Additionally, it is unknown whether the effectiveness of cryotherapy depends on the applied temperature. This study aimed to clarify the biological effects of cryotherapy and to examine the therapeutic effects of cryotherapy applied at different temperatures in rats. METHODS: This was an experimental study using a rat knee joint arthritis model. Thirty-five Wistar rats were randomly divided into arthritis (AR), arthritis with 5°C cryotherapy (CR-5), arthritis with 10°C cryotherapy (CR-10), and sham-arthritis control (CON) groups. Arthritis was induced by injecting a mixture of kaolin/carrageenan into the right knee joint. Cryotherapy was applied for 7 days starting the day after injection by immersing the right knee joint in 5°C or 10°C water. Joint transverse diameter, pressure pain threshold, and pain-related behaviors were assessed for 7 days. The number of CD68-positive cells in the knee joint and the expression of calcitonin gene-related peptide in the spinal dorsal horn 8 days after injection were analyzed by immunohistochemical staining. RESULTS: Improvements in transverse diameter, pressure pain threshold, and pain-related behaviors were observed in the CR-5 and CR-10 groups on the 3rd day compared with the AR group. The number of CD68-positive cells and the expression of calcitonin gene-related peptide in the CR-5 and CR-10 groups were significantly decreased compared with the AR group. There were no significant differences in all results between the CR-5 and CR-10 groups. CONCLUSIONS: Cryotherapy can ameliorate inflammatory pain through reduction of synovium and central sensitization. Additionally, the effects of cryotherapy lower than 10°C are observed independent of applied temperature. IMPACT: Cryotherapy may be beneficial as a physical therapy modality for pain and swelling management in the acute phase of inflammation. Translational human study is needed to determine the effective cryotherapy temperature for the inflammatory pain.