Introduction: Patients with peripheral artery disease (PAD) often complain of reduced physical activity (PA) despite improvements in intermittent claudication after successful endovascular treatment (EVT). Sarcopenia resulting from chronic ischemia can affect post-EVT PA levels. Objective: This study aims to assess the association between sarcopenia and post-EVT PA levels. Methods: One hundred five patients with PAD were consecutively enrolled in this study. PA was assessed using the post-EVT step count and the pre-EVT International Physical Activity Questionnaire. Sarcopenia was diagnosed based on the Asia Working Group for Sarcopenia and defined as low muscle mass and strength, and/or slow walking speed. The patients were categorized into three groups: 1) patients with sarcopenia (Sarcopenia Group); 2) patients with only low muscle mass or strength, and/or slow walking speed (Suspected-Sarcopenia Group); and 3) patients who did not fulfill all the sarcopenia criteria (No-Sarcopenia Group). Results: Proportions of patients in the Sarcopenia, Suspected-Sarcopenia, and No-Sarcopenia Groups were 31.4, 38.1, and 30.5%, respectively. After controlling for potential confounders, the Sarcopenia Group demonstrated significantly lower step counts than the Suspected-Sarcopenia Group (p = .016) and No-Sarcopenia Group (p = .009). Conclusions: Our findings indicate that patients with PAD and sarcopenia require rehabilitation strategies to enhance physical performance.

Delayed onset muscle soreness (DOMS) develops after performing unaccustomed eccentric exercises. Animal studies have shown that DOMS is mechanical hyperalgesia through nociceptor sensitization induced by nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) upregulated by cyclooxygenase-2 (COX-2). However, no previous study has investigated these in relation to DOMS in humans. This study compared the first and second bouts of one-leg eccentric cycling (ECC) for changes in NGF, GDNF, and COX-2 mRNA in the vastus lateralis (VL). Seven healthy adults (18-40 years) performed two bouts of ECC (10 sets of 50 contractions) with 80% maximal voluntary concentric peak torque separated by 2 weeks (ECC1, ECC2). Muscle soreness that was assessed by a visual analog scale and maximal voluntary isometric contraction (MVC) torque of the knee extensors were measured before, immediately after (MVC only), 24 and 48 h post-exercise. Muscle biopsy was taken from the VL before the first bout from nonexercised leg (control) and 24 h after each bout from the exercised leg, and analyzed for NGF, GDNF, and COX-2 mRNA. Peak DOMS was more than two times greater and MVC torque at 48 h post-exercise was approximately 20% smaller after ECC1 than ECC2 (p < 0.05), suggesting the repeated bout effect. NGF mRNA level was higher (p < 0.05) post-ECC1 (0.79 +/- 0.68 arbitrary unit) than control (0.06 +/- 0.07) and post-ECC2 (0.08 +/- 0.10). GDNF and COX-2 mRNA did not show significant differences between control, post-ECC1, and post-ECC2. These results suggest that an increase in NGF is associated with the development of DOMS in humans.

Background This nonrandomized pilot study explored how whole-body eccentric resistance exercise training (ECC-RT) would change physical fitness and health parameters of older adults with metabolic syndrome symptoms. We hypothesized that ECC-RT would effectively improve neuromuscular and cardio-metabolic parameters. Methods Six men and 11 women aged between 62 and 79 (70.0 ± 5.0) years with body mass index >25 kg · m−2, dyslipidemia, and some indications of metabolic syndrome participated in this study. All performed 8 ECC-RT exercises of the major muscle groups twice a week for 8 weeks with a gradual increase in intensity from 10% to 100% of their maximal concentric strength assessed by 1-repetition maximum (1-RM) for each exercise. Before and after the training intervention, 1-RM strength of all exercises, physical function tests, sensory organization test (SOT) for balance, body composition, and some cardio-metabolic blood markers were measured. Results All participants completed 16 training sessions without any injuries or adverse effects. The concentric 1-RM strength increased (P < 0.05) for all exercises from baseline by 34.1% ± 13.8% (lateral pulldown) to 115.8% ± 108.7% (calf raise). Significant (P < 0.05) improvement of 400-m walk (12.8% ± 6.7%), repeated chair rise (18.6% ± 16.4%), timed up and go (13.6% ± 6.0%), and vestibular (26.1% ± 37.9%) and total score (6.5% ± 8.3%) in SOT were evident, although large variations in responses were observed among participants. However, no significant changes in body composition and blood markers were found. Conclusion The ECC-RT was tolerable for all participants and was effective for improving muscle strength and some physical function tests, but did not affect the metabolic syndrome parameters, possibly because of the short intervention period and small sample size.

Cast immobilization causes sensory hypersensitivity, which is also a symptom of neuropathic pain and chronic pain. However, the mechanisms underlying immobilization-induced hypersensitivity remain unclear. The present study investigated the role of dopamine neurotransmission in the nucleus accumbens shell (NAcSh) of rats with cast immobilization-induced mechanical hypersensitivity using in vivo microdialysis. Cast immobilization of the hind limb decreased the paw withdrawal threshold (PWT). Mechanical stimulation of the cast-immobilized hind limb induced a decrease in dopamine in the NAcSh, and this decrease was associated with the upregulation of presynaptic D2-like receptors. A D2-like receptor antagonist infused into the NAcSh reversed the decrease in PWT in rats with cast immobilization, whereas a D2-like receptor agonist infused into the NAcSh induced a decrease in PWT in control rats. In addition, the expression of the D2 receptor (Drd2) mRNA in the NAcSh was increased by cast immobilization. Importantly, systemic administration of the D2-like receptor antagonist reversed the decrease in PWT in rats with cast immobilization. As dopamine levels regulated by presynaptic D2-like receptors did not correlate with the PWT, it is presumed that the D2-like receptor antagonist or agonist acts on postsynaptic D2-like receptors. These results suggest that immobilization-induced mechanical hypersensitivity is attributable to the upregulation of postsynaptic D2-like receptors in the NAc. Blockade of D2-like receptors in the NAcSh is a potential therapeutic strategy for immobilization-induced hypersensitivity.

We examined changes in plasma creatine kinase (CK) activity, hydroxyproline and cell-free DNA (cfDNA) concentrations in relation to changes in maximum voluntary isometric contraction (MVIC) torque and delayed-onset muscle soreness (DOMS) following a session of volume-matched higher- (HI) versus lower-intensity (LI) eccentric cycling exercise. Healthy young men performed either 5 × 1-min HI at 20% of peak power output (n = 11) or 5 × 4-min LI eccentric cycling at 5% of peak power output (n = 9). Changes in knee extensor MVIC torque, DOMS, plasma CK activity, and hydroxyproline and cfDNA concentrations before, immediately after, and 24–72 h post-exercise were compared between groups. Plasma CK activity increased post-exercise (141 ± 73.5%) and MVIC torque decreased from immediately (13.3 ± 7.8%) to 48 h (6.7 ± 13.5%) post-exercise (P < 0.05), without significant differences between groups. DOMS was greater after HI (peak: 4.5 ± 3.0 on a 10-point scale) than LI (1.2 ± 1.0). Hydroxyproline concentration increased 40–53% at 24–72 h after both LI and HI (P < 0.05). cfDNA concentration increased immediately after HI only (2.3 ± 0.9-fold, P < 0.001), with a significant difference between groups (P = 0.002). Lack of detectable methylated HOXD4 indicated that the cfDNA was not derived from skeletal muscle. No significant correlations were evident between the magnitude of change in the measures, but the cfDNA increase immediately post-exercise was correlated with the maximal change in heart rate during exercise (r = 0.513, P = 0.025). Changes in plasma hydroxyproline and cfDNA concentrations were not associated with muscle fiber damage, but the increased hydroxyproline in both groups suggests increased collagen turnover. cfDNA may be a useful metabolic-intensity exercise marker.

Abstract Background The benefits of resistance training for patients with type 2 diabetes (T2D) are well documented; however, the effects of exercise with different muscle contraction types such as eccentric versus concentric contractions on physiological outcomes for this population are not clear. This study compared eccentric-only (ECC) and concentric-only resistance training (CON) to test the hypothesis that ECC would be superior to CON to improve insulin sensitivity, lipid profile, body composition, muscle strength and physical function of patients with T2D. Methods Adults with T2D (50–79 years) were allocated to the ECC (n = 9) or CON group (n = 9). Resistance exercises (chest press, lateral pulldown, bicep curl, triceps extension, leg extension, leg curl, calf raise, abdominal crunch) consisting of 2–3 sets of 10 eccentric-only (5 s) or concentric-only contractions (1–2 s) was performed twice a week for 12 weeks. Changes in blood biomarkers, body composition, muscle strength and physical function from pre- to post-intervention were compared between groups. Results Overall rating of perceived exertion (RPE, 1–10 Borg scale) was lower (p < 0.05) for ECC (2.9 ± 1.2) than CON (5.4 ± 1.1). No significant changes in blood biomarkers were found for both groups. Lean mass increased [effect size (ES) = 0.148, ECC 3.2 ± 6.9%; CON 3.6 ± 2.3%], and fat mass decreased (ES = 0.545, ECC − 6.1 ± 12.4%; CON − 7.1 ± 16.4%) (p < 0.05) similarly. One-repetition maximal strength of each exercise increased (p < 0.05) for both ECC (12–37%) and CON (27–68%). Both groups improved (p < 0.05) 6-min walk distance (ES = 0.083, ECC 12.2 ± 2.3%; CON 12.5 ± 15.3%) and chair rise time (ES = 0.463, ECC − 13.4 ± 25.4%; CON − 20.0 ± 53.3%) but only ECC improved (p < 0.05) the timed up-and-go test (− 11.3 ± 13.6%, ES 0.014). No significant changes in balance tests were found for both groups. Conclusion These results did not fully support the hypothesis but showed that ECC was as effective as CON to improve body composition, muscle strength, and physical function with lesser RPE. Future studies should investigate whether larger differences between ECC and CON are evident when increasing the exercise frequency and matching the intensities of the two-exercise protocols. Trial registration ACTRN12621001026819 (retrospectively registered on 5th Aug 2021).

目的：血管内治療（EVT）を受ける末梢動脈疾患（PAD）患者の身体機能の実態およびEVT術前の身体活動との関連について明らかにする．

We compared high- and low-intensity eccentric cycling (ECC) with the same mechanical work for changes in muscle function and muscle soreness, and examined the changes after subsequent high-intensity ECC. Twenty men performed either high-intensity ECC (1 min × 5 at 20% of peak power output: PPO) for two bouts separated by 2 weeks (H–H, n = 11), or low-intensity (4 min × 5 at 5% PPO) for the first and high-intensity ECC for the second bout (L–H, n = 9). Changes in indirect muscle damage markers were compared between groups and bouts. At 24 h after the first bout, both groups showed similar decreases in maximal isometric (70° knee angle,  − 10.6 ± 11.8%) and isokinetic ( − 11.0 ± 8.2%) contraction torque of the knee extensors (KE), squat ( − 7.7 ± 10.4%) and counter-movement jump ( − 5.9 ± 8.4%) heights (p < 0.05). Changes in KE torque and jump height were smaller after the second than the first bout for both the groups (p < 0.05). Increases in plasma creatine kinase activity were small, and no significant changes in vastus lateralis or intermedius thickness nor ultrasound echo-intensity were observed. KE soreness with palpation was greater (p < 0.01) in H–H (peak: 4.2 ± 1.0) than L–H (1.4 ± 0.6) after the first bout, but greater in L–H (3.6 ± 0.9) than H–H (1.5 ± 0.5) after the second bout. This was also found for muscle soreness with squat, KE stretch and gluteal palpation. The high- and low-intensity ECC with matched mechanical work induced similar decreases in muscle function, but DOMS was greater after high-intensity ECC, which may be due to greater extracellular matrix damage and inflammation.

We focused on the analgesic effect of hot packs for mechanical hyperalgesia in physically inactive rats. Male Wistar rats were randomly divided into four groups: control, physical inactivity (PI), PI + sham treatment (PI + sham), and PI + hot pack treatment (PI + hot pack) groups. Physical inactivity rats wore casts on both hind limbs in full plantar flexed position for 4 weeks. Hot pack treatment was performed for 20 min a day, 5 days a week. Although mechanical hyperalgesia and the up-regulation of NGF in the plantar skin and gastrocnemius muscle were observed in the PI and the PI + sham groups, these changes were significantly suppressed in the PI + hot pack group. The present results clearly demonstrated that hot pack treatment was effective in reducing physical inactivity-induced mechanical hyperalgesia and up-regulation of NGF in plantar skin and gastrocnemius muscle.

Changed vascular functions have been reported in several pathological conditions, such as chronic regional pain syndrome, obstructive vascular disease, and inflammation. Our previous experiments also showed that electrical stimulation of the lumbar sympathetic trunk (sympathetic stimulation: SS), which normally induces a decrease in blood flow (BF), caused a BF increase in about half of the measured sites in rats persistently inflamed with complete Freund's Adjuvant (AI rats). We also showed that the BF-increase response was only partially suppressed by the alpha1 antagonist at a higher dosage, suggesting the involvement of nonadrenergic mechanisms. We hypothesize that nonadrenergic mechanisms mediating vasodilatation might involve a vasodilating neuropeptide such as substance P (SP) that is released from sympathetic nerve terminals. In this experiment, we conducted an examination using an NK-1 receptor antagonist to determine whether SP plays any role in changed response to SS in AI rats, and also an immunohistochemical examination of whether SP is expressed in the lumbar sympathetic nerve ganglia (SG) of AI rats. The administration of an NK-1 receptor antagonist, CP-96,345, significantly reduced the BF-increase response to SS in AI rats, but its inactive enantiomer, CP-96,344, had no effect. Immunohistochemistry for SP revealed that SP-ir positive SG neurons (mean 13 neurons/rat) were found in 5 of 8 AI rats, whereas only one neuron was stained in 8 control rats. These results suggest that NK-1 receptor activation is involved in the BF-increase response to SS, and that this activation is in part mediated by SP from lumbar SG that was synthesized de novo in inflamed animals.

There is some evidence that the sympathetic nervous system plays a role in the development and/or maintenance of painful states, and that sympathetic nervous function is altered in these conditions. Our previous experiments showed that electrical stimulation of the lumbar sympathetic trunk (sympathetic stimulation: SS), which normally induces a decrease in blood flow (BF), induced a BF increase in all adjuvant-inflamed rats. Such rats are one model of persistent pain. This mechanism for the BF-increase response to SS involves both α-adrenergic and non-adrenergic receptors. In the present experiment we examined whether BF was increased by SS in another animal model of pain, which was produced by placing loosely tied ligatures around the common sciatic nerve, and whether the BF response involved the al-adrenoceptor. We found SS induced both increased and decreased BF responses in this pain model. Both responses were inhibited by al-adrenoceptor antagonist. This result suggests the possibility that the plantar BF-increase response occurs as a secondary effect following vasoconstriction at another site.

Clinical muscular pain such as stiff neck and lumbago is often treated with massage, stretch, and vibration; however, the effectiveness of these procedures and their action mechanisms remain unclear. We consider it important to quantitatively evaluate the effectiveness of these procedures using experimentally induced muscular pain. Exercise-induced pain has been used as a model of muscular pain. In the present experiment, we used this model to evaluate the effect of vibration, which is used in physical therapy. Muscle soreness was induced by exercise of the upper arm using a weight belt, and changes in the muscle were evaluated using limb circumference, joint angle, strength of muscle soreness, dimensions of muscle and blood flow before and after exercise and vibration. The present exercise protocol induced delayed onset muscle soreness 1 day after exercise. Vibration given immediately and 2 days after exercise widened the limited range of motion, decreased muscle soreness in full flexion and extension positions, increased blood flow in the deep tissues involving muscle and another connective tissues, increased the thickness of subcutaneous tissues, and tended to decrease the thickness of flexors. However, in contrast to our clinical experience, these effects did not last long after vibration. The reason for this might be that the kind of pain was different.

There is some evidence that the sympathetic nervous system plays a role in the development and/or maintenance of painful states, and that sympathetic nervous function is altered in these conditions. Our previous experiments showed that electrical stimulation of the lumbar sympathetic trunk (sympathetic stimulation: SS), which normally induces a decrease in blood flow (BF) of plantar skin, induced its BF increase in about 50% of adjuvant-inflamed rats. To investigate the mechanism of this BF-increase response, we examined whether noradrenaline (NA) plays any role in this changed response to SS, and which receptor subtype is involved. We measured paw cutaneous BF response with a laser Doppler flowmeter in rats chronically inflamed with complete Freund's adjuvant. SS induced the BF-increase response in 50-67% of measured sites. Close-arterially injected NA induced the BF-increase response at dosages between 10-100 ng/kg only at the sites with the BF-increase response to SS. The BF-increase and -decrease responses to NA was significantly reduced after the close-arterial injection of either alpha1- or alpha2-adrenoceptor antagonists (p lt; 0.05, respectively). In contrast, although the BF-decrease responses to SS were significantly reduced by administration of alpha1- and alpha2-adrenoceptor antagonist, BF-increase response was reduced only by alpha1-adrenoceptor antagonist, and that only at a higher dose. In addition, the beta-adrenoceptor antagonist had no effects on both responses. These results suggest that the BF-increase response to SS involves, additionally to NA, a non-adrenergic mechanism.

We have previously shown that the inhibitory respiratory response, which we call post-stimulus suppression, is induced by nociceptive muscular afferents. This phenomenon is thought to be caused by a negative feedback induced by excessive afferent inputs. In the present study, we investigated whether augmented levels of prestimulus respiration would influence the magnitude of poststimulus suppression by recording the phrenic nerve discharges in chloralose-urethane anesthetized, vagotomized, paralyzed and artificially ventilated cats. The respiratory level was augmented by means of either hypercapnia, hypoxia or naloxone administration, all of which markedly facilitated the peak amplitude (PK) of integrated phrenic discharges, neural tidal volume. When the electrical stimulation of thin-fiber muscular afferents was performed at these augmented PK levels, the magnitude of poststimulus suppression in the PK was markedly attenuated without consistently altering the facilitatory response during the stimulation period. It seems that the facilitatory component of the augmented level of resting respiration may reduce the inhibitory component of poststimulus suppression. The results indicate that prestimulus respiratory activity is an important factor in determining the magnitude of poststimulus suppression.

In adjuvant arthritic (AA) rats, an abnormal responsiveness of nociceptors (C-fibre polymodal receptors) to sympathetic activities, i.e., alpha 2-adrenoceptor mediated activation of C-fibre polymodal receptors (CPRs), has been observed. The present investigations were undertaken to determine if a similar plastic change would occur in the cutaneous vascular system in the rat chronic inflammation model. The vascular responses were measured by a laser-Doppler flowmeter in the hindpaw skin of the AA rats after electrical stimulation of lumbar sympathetic trunk (sympathetic stimulation). In control non-arthritic rats, the sympathetic stimulation caused decrease in blood flow of the skin (SkBF) in all animals tested (n = 7). On the other hand, the sympathetic stimulation in the AA rats caused both increase (n = 15) as well as decrease (n = 11) in SkBF. In contrast to the abnormal responsiveness of CPRs, the intra-arterial injection of noradrenaline caused the expected decrease in SkBF in all animals tested, and in no instances increases in SkBF were observed. To determine whether activation of nitric oxide (NO), which is known to be a potent endogenous vasodilatation substance, was involved in the vasodilating effect to sympathetic stimulation, an inhibitor of NO synthase, NG-monomethyl-L-arginine (L-NMMA), was applied systemically. L-NMMA significantly increased baseline blood pressure in the control and the AA rats, but it did not significantly alter the SkBF in the control or the AA rats after the sympathetic stimulation, suggesting that NO is not a mediator in the vasoactive responses. The results of the current studies showed for the first time that electrical stimulation of the lumbar sympathetic trunk causes vasodilatation in the skin of the AA rats. This abnormal responsiveness of regional SkBF after sympathetic stimulation was not mediated by adrenergic or NO system.