Junya Sakamoto

Effects of Therapeutic Ultrasound on Joint Mobility and Collagen Fibril Arrangement in the Endomysium of Immobilized Rat Soleus Muscle

This study examined effects of therapeutic ultrasound on joint mobility and collagen fibril arrangement in the endomysium of immobilized rat soleus muscle. Twenty-two male Wistar rats were divided randomly into control (n = 5) and experimental groups (n = 17). In the experimental group, bilateral ankle joints of each rat were fixed in full plantar flexion with a plaster cast over a 4-wk period. Five animals in the experimental group were immobilized throughout the 4-wk (immobilization group) period, whereas the remaining rats in the experimental group were randomly divided into the ultrasound (US, n = 6) and sham (n = 6) treatment groups. Under anesthesia, continuous ultrasonic energy (frequency, 1 MHz; intensity, 1.0 W/cm(2)) was delivered to the triceps surae muscle of the US group for 15 min per d, 6 d per wk over the 4-wk immobilization period. Ultrasonic energy was not delivered to the triceps surae muscle in sham animals; only the transducer head was moved. Ankle joint mobility on dorsiflexion in the immobilization, sham and US groups was significantly smaller than that of the control group, whereas in the US group, this parameter was significantly greater than in the immobilization and sham groups. Collagen fibril arrangement in the endomysium of the control and US groups was longitudinal to the axis of the muscle fibers; in contrast, it was circumferential in the immobilization and sham groups. Our findings revealed that joint immobilization induces decreased joint mobility and collagen fibril movement in the endomysium; furthermore, ultrasound treatment can prevent these changes. We hypothesized that therapeutic ultrasound during the immobilization process may inhibit deterioration of muscle contracture.

Immobilization-Induced Cartilage Degeneration Mediated Through Expression of Hypoxia-Inducible Factor-1α, Vascular Endothelial Growth Factor, and Chondromodulin-I

Immobilization results in thinning of the articular cartilage and cartilage degeneration, although the exact mechanisms are not clear yet. Hypoxia is thought to contribute to the degeneration of articular cartilage. We investigated the roles of hypoxia inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF), and the newly cloned antiangiogenic factor, chondromodulin-I (ChM-1), in cartilage degeneration in immobilized joints. Male Wistar rats (n = 30, 12-week-old) were divided randomly into the control group (n = 10), immobilization group (n = 10), and continuous passive motion (CPM) group (n = 10). In the immobilization group, the ankle joints were fixed in full plantar flexion with plaster casts for 4 weeks. In the CPM group, the ankle casts were removed during the immobilization period and the ankle joints were subjected to CPM. Significant thinning of the articular cartilage was noted in the immobilization group but not in the control or CPM group. In the immobilized group, vascular channels were found in the area between the calcified cartilage zone and the subchondral bone. The densities of HIF-1α—and VEGF-immunostained cells were higher in the immobilized group than the other two groups. In contrast, low expression of ChM-1 was detected in the articular cartilage of the immobilized group compared with the control and CPM group. Our results showed that immobilization induces thinning of the articular cartilage and appearance of vascular channel, in areas with balanced expression of HIF-1α/VEGF and ChM-1.

Investigation and Macroscopic Anatomical Study of Referred Pain in Patients with Hip Disease

[Purpose] The aim of this study was to examine the incidence and patterns of referred pain in patients with hip disease, as well as the nerve distribution in the hip and knee joints of 2 cadavers. [Subjects and Methods] A total of 113 patients with hip joint disease were included in the investigation. The incidence of regional pain and referred pain patterns were evaluated before and after arthroplasty. Two cadavers were macroscopically observed to verify the nerve innervation of the hip and knee joints. [Results] Anterior knee pain was observed preoperatively in 13.3% (in resting) and 33.6% (in motion) of the patients, which was comparable with the incidence of greater trochanter pain. In addition, the preoperative incidence rates of knee pain in resting and motion markedly decreased postoperatively. Of note is the remarkable incidence of pain radiating to the ventral lower limb. An anteromedial innervation was determined in the cadavers by the articular branches of the obturator and femoral nerve, which supply small branches to the knee joints. [Conclusion] Our results suggest that the distribution of the incidence of pain among the patients with hip disease is diverse owing to the sensory distribution of the femoral and obturator nerves.

Hyperalgesia in an immobilized rat hindlimb: Effect of treadmill exercise using non-immobilized limbs

Cast immobilization of limbs causes hyperalgesia, which is a decline of the threshold of mechanical and thermal mechanical stimuli. The immobilization-induced hyperalgesia (IIH) can disturb rehabilitation and activities of daily living in patients with orthopedic disorders. However, it is unclear what therapeutic and preventive approaches can be used to alleviate IIH. Exercise that activates the descending pain modulatory system may be effective for IIH. The purpose of this study was to investigate the effects of treadmill exercise during the immobilization period, using the non-immobilized limbs, on IIH. Thirty-six 8-week-old Wistar rats were randomly divided into (1) control, (2) immobilization (Im), and (3) immobilization and treadmill exercise (Im+Ex) groups. In the Im and Im+Ex groups, the right ankle joints of each rat were immobilized in full plantar flexion with a plaster cast for an 8-week period. In the Im+Ex group, treadmill exercise (15 m/min, 30 min/day, 5 days/week) was administered during the immobilization period while the right hindlimb was kept immobilized. Mechanical hyperalgesia was measured using von Frey filaments every week. To investigate possible activation of the descending pain modulatory system, beta-endorphin expression levels in hypothalamus and midbrain periaqueductal gray were analyzed. Although IIH clearly occurred in the Im group, the hyperalgesia was partially but significantly reduced in the Im+Ex group. Beta-endorphin, which is one of the endogenous opioids, was selectively increased in the hypothalamus and midbrain periaqueductal gray of the Im+Ex group. Our data suggest that treadmill running using the non-immobilized limbs reduces the amount of hyperalgesia induced in the immobilized limb even if it is not freed. This ameliorating effect might be due to the descending pain modulatory system being activated by upregulation of beta-endorphin in the brain.

Upregulation of interleukin-1β/transforming growth factor-β1 and hypoxia relate to molecular mechanisms underlying immobilization-induced muscle contracture.

Introduction: In this study we investigated the molecular mechanism underlying muscle contracture in rats. Methods: The rats were divided into immobilization and control groups, and soleus muscles of the right and left sides were selected for analyses. Results: The levels of CD11b and α‐SMA protein, IL‐1β, and TGF‐β1 mRNA, and type I and III collagen protein and mRNA were significantly greater in the immobilization group than in the control group at all time‐points. HIF‐1α mRNA levels were significantly higher in the immobilization group at 4 weeks. Moreover, HIF‐1α, α‐SMA, and type I collagen levels were significantly higher at 4 weeks than at 1 and 2 weeks in the immobilization group. Conclusions: In the early stages of immobilization, upregulation of IL‐1β/TGF‐β1 via macrophages may promote fibroblast differentiation that could affect muscle contracture. The soleus muscle became hypoxic in the later stages of immobilization, suggesting that hypoxia influences the progression of muscle contracture. Muscle Nerve 52:419–427, 2015

Sensory hyperinnervation and increase in NGF, TRPV1 and P2X3 expression in the epidermis following cast immobilization in rats

Cast immobilization is known to induce pain in humans and experimental animal models; however, the detailed mechanisms underlying this pain have yet to be elucidated. Recently, several lines of evidence have indicated that morphological changes in sensory innervation and changes in the expression of pain‐related molecules in the epidermis are related to certain painful conditions. The aim of the present study was to temporally investigate the histological changes in the glabrous skin of the rat hind paw after 1, 2 and 4 weeks of ankle joint immobilization by casting.

Effects of joint immobilization on changes in myofibroblasts and collagen in the rat knee contracture model

The purpose of this study was to examine the time‐dependent changes in the development of joint capsule fibrosis and in the number of myofibroblasts in the joint capsule after immobilization, using a rat knee contracture model. Both knee joints were fixed in full flexion for 1, 2, and 4 weeks (immobilization group). Untreated rats were bred for each immobilization period (control group). Histological analysis was performed to evaluate changes in the amount and density of collagen in the joint capsule. The changes in type I and III collagen mRNA were examined by in situ hybridization. The number of myofibroblasts in the joint capsule was assessed by immunohistochemical methods. In the immobilization group, the amount of collagen increased within 1 week and the density of collagen increased within 2 weeks, as compared with that in the control group. Type I collagen mRNA‐positive cell numbers in the immobilization group increased at all time points. However, type III collagen mRNA‐positive cell numbers did not increase. Myofibroblasts in the immobilization group significantly increased compared with those in the control group at all time points, and they increased significantly with the period of immobilization. These results suggest that joint capsule fibrosis with overexpression of type I collagen occurs and progresses within 1 week after immobilization, and an increase in myofibroblasts is related to the mechanism of joint capsule fibrosis. The findings suggest the need for a treatment targeting accumulation of type I collagen associated with an increase in myofibroblasts.

Factors associated with chronic musculoskeletal pain in Japanese community-dwelling older adults: A cross-sectional study

Abstract Identifying older adults with chronic musculoskeletal pain (CMP) earlier is urgent because CMP is reportedly associated with deterioration in physical function, poor psychological status, and low physical activity level. The objective of this study was to identify factors that were most strongly associated with CMP in Japanese community-dwelling older adults. Using a cross-sectional design, we assessed 263 older adults (mean age = 79.1 ± 5.9 years, 85.9% women) who participated in community exercise classes. Participants’ physical function, psychological status, and activity levels were evaluated as outcome measures using a variety of tests and instruments. These assessments were conducted prior to beginning the exercise intervention program and compared participants with and without CMP. Additionally, relevant participant characteristics were collected and analyzed. In this study, CMP was defined as the presence of related symptoms within the past month that continued for at least 6 months and corresponded to a numerical rating scale of at least 5 or more at the site of maximum pain. A total of 143 (54.4%) participants met the criteria for CMP, and a high number of them had chronic lower back pain (64.3%). Outcome measures for the CMP group were significantly worse than for the non-CMP group (P < .05). Logistic regression analysis revealed that the Pain Catastrophizing Scale helplessness domain scores (odds ratio: 1.20, 95% confidence interval: 1.09–1.32) with an estimated value of 10 points was the factor most significantly associated with the presence of CMP. These findings suggest that assessment of the helplessness associated with pain-related catastrophizing is important for identification and the creation of interventions for older adults with CMP.

Effects of Vibration Therapy on Immobilization-Induced Hypersensitivity in Rats

Background Cast immobilization induces mechanical hypersensitivity, which disturbs rehabilitation. Although vibration therapy can reduce various types of pain, whether vibration reduces immobilization-induced hypersensitivity remains unclear. Objective The purpose of this study was to investigate the preventive and therapeutic effects of vibration therapy on immobilization-induced hypersensitivity. Design The experimental design of the study involved conducting behavioral, histological, and immunohistochemical studies in model rats. Methods Thirty-five Wistar rats (8 weeks old, all male) were used. The right ankle joints of 30 rats were immobilized by plaster cast for 8 weeks, and 5 rats were used as controls. The immobilized rats were divided randomly into the following 3 groups: (1) immobilization-only group (Im, n=10); (2) vibration therapy group 1, for which vibration therapy was initiated immediately after the onset of immobilization (Im+Vib1, n=10); and (3) vibration therapy group 2, for which vibration therapy was initiated 4 weeks after the onset of immobilization (Im+Vib2, n=10). Vibration was applied to the hind paw. The mechanical hypersensitivity and epidermal thickness of the hind paw skin were measured. To investigate central sensitization, calcitonin gene-related peptide (CGRP) expression in the spinal cord and dorsal root ganglion (DRG) was analyzed. Results Immobilization-induced hypersensitivity was inhibited in the Im+Vib1 group but not in the Im+Vib2 group. Central sensitization, which was indicated by increases in CGRP expression in the spinal cord and the size of the area of CGRP-positive neurons in the DRG, was inhibited in only the Im+Vib1 group. Epidermal thickness was not affected by vibration stimulation. Limitations A limitation of this study is that the results were limited to an animal model and cannot be generalized to humans. Conclusions The data suggest that initiation of vibration therapy in the early phase of immobilization may inhibit the development of immobilization-induced hypersensitivity.

Effects of Exercise Training Combined with Increased Physical Activity to Prevent Chronic Pain in Community-Dwelling Older Adults: A Preliminary Randomized Controlled Trial

Objective With the aim of developing a chronic pain prevention program, this randomized controlled trial examined whether exercise training combined with increased physical activity more effectively improves pain and physical activity than exercise training alone in community-dwelling older adults without chronic pain. Methods We randomized 76 older adults without chronic pain into an intervention group (n=38) involving exercise training combined with increased physical activity and a control group (n=38) involving exercise training alone. The exercise training comprised weekly 60-min sessions for 12 weeks. The program to increase physical activity required participants to record their daily step counts using pedometers. Pain intensity, total number of pain sites, and physical activity were assessed before and 12 weeks after the intervention. Results A time-by-group interaction was found for physical activity, with the intervention group showing significant improvement (p < 0.05). The intervention group also showed greater improvement in pain intensity and total number of pain sites at 12 weeks after intervention than the control group (p < 0.05). Conclusions In older adults without chronic pain, exercise training combind with increased physical activity improves key outcome indicators more effectively than exercise training alone. “This trial is registered with UMIN000018503.”