Enhanced serum levels of tumor necrosis factor-α, interleukin-1ß, and -6 in sarcopenia: alleviation through exercise and nutrition intervention.

BACKGROUND: Limited research has been conducted on the post-intervention inflammatory status in sarcopenic patients, despite previous studies revealing elevated pro-inflammatory markers. This study aimed to investigate the potential elevation of specific pro-inflammatory cytokines in sarcopenic patients and evaluate the effects of exercise and nutritional support interventions on these cytokine levels. METHODS: In this post-hoc analysis of a randomized controlled trial (RCT), 57 individuals with sarcopenia from the RCT and 57 non-sarcopenic participants from the same geriatric community cohort that did not participate in the RCT were enrolled. Grip strength and body composition measurements were recorded. Tumor necrotizing factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-15 levels were assessed at baseline for both groups and after a 12-week intervention consisting of resistive exercise and supplementation with branched-chain amino acids, calcium, and vitamin D3 in the patients with sarcopenia. RESULTS: The sarcopenic group demonstrated significantly lower body weight, body mass index, grip strength, and skeletal muscle mass index. Moreover, sarcopenic patients exhibited higher levels of TNF-α (p=0.007), IL-1ß (p<0.001), and IL-6 (p<0.001), while no significant difference was observed in IL-15 (p=0.345) between participants with and those without sarcopenia. Following the intervention, the sarcopenic group experienced significant improvements in grip strength and skeletal muscle mass index with a notable reduction in TNF-α (p=0.003), IL-1ß (p=0.012) and IL-6 (p=0.001) levels. CONCLUSIONS: Sarcopenic patients exhibit elevated levels of TNF-α, IL-1ß, and IL-6, which declined after nutrition support and exercise interventions. However, further research is necessary to evaluate the long-term impact of these interventions on cytokine levels.

A role for substance P and acid-sensing ion channel 1a in prolotherapy with dextrose-mediated analgesia in a mouse model of chronic muscle pain.

ABSTRACT: Prolotherapy is widely used in pain control and tissue repair in pain medicine. The classical mode is injection with hypertonic dextrose in muscle or perimysium. However, the analgesic mechanism is still not known. Here, we successfully established dextrose-mediated antinociception in a mouse model of fibromyalgia. The antinociceptive effects of dextrose injections were evaluated in a mouse model of fibromyalgia, in which bilateral chronic mechanical hyperalgesia was induced by unilateral intramuscular acid injection. The injectant (dextrose), dose (≥5%), and volume (>10 µL), but not osmolarity, were essential for the prolotherapy. Further studies showed that the activation of acid-sensing ion channel 1a (ASIC1a), neural activation, and the release of substance P from muscle afferents were required in the dextrose-induced reduction of mechanical hypersensitivity. Both pharmacological blockade and genetic deletion of ASIC1a or substance P as well as lidocaine abolished the dextrose-induced antinociception in mice with chronic hyperalgesia. Moreover, intramuscular dextrose injection induced phosphorylated extracellular signal-regulated kinase expression in dorsal root ganglion neurons expressing substance P; the phosphorylated extracellular signal-regulated kinase expression was inhibited by the ASIC1a antagonist PcTx1. The optimal settings for prolotherapy in fibromyalgia-like pain are dextrose dependent and volume dependent, and the peripheral antinociception involves ASIC1a and substance P signaling in muscle afferents. This study suggests a possible mechanism of action of dextrose prolotherapy in noninflammatory muscle pain such as fibromyalgia and provides insights into treating other types of chronic pain.

Diagnosing sarcopenia: Functional perspectives and a new algorithm from the ISarcoPRM.

Sarcopenia is an important public health problem, characterized by age-related loss of muscle mass and muscle function. It is a precursor of physical frailty, mobility limitation, and premature death. Muscle loss is mainly due to the loss of type II muscle fibres, and progressive loss of motor neurones is thought to be the primary underlying factor. Anterior thigh muscles undergo atrophy earlier, and the loss of anterior thigh muscle function may therefore be an antecedent finding. The aim of this review is to provide an in-depth (and holistic) neuromusculoskeletal approach to sarcopenia. In addition, under the umbrella of the International Society of Physical and Rehabilitation Medicine (ISPRM), a novel diagnostic algorithm is proposed, developed with the consensus of experts in the special interest group on sarcopenia (ISarcoPRM). The advantages of this algorithm over the others are: special caution concerning disorders related to the renin-angiotensin system at the case finding stage; emphasis on anterior thigh muscle mass and function loss; incorporation of ultrasound for the first time to measure the anterior thigh muscle; and addition of a chair stand test as a power/performance test to assess anterior thigh muscle function. Refining and testing the algorithm remains a priority for future research.

Effectiveness of early versus delayed exercise and nutritional intervention on segmental body composition of sarcopenic elders - A randomized controlled trial.

BACKGROUND & AIMS: Although resistance training with nutritional support is considered the best treatment option for sarcopenia, the importance of home-based exercise should not be overlooked. For managing sarcopenia, a fundamental issue is whether home-based exercise or a supervised training program should be administered first. Therefore, the present trial aimed to compare the effect of early versus delayed exercise intervention with nutritional support on the physical performance and body composition of sarcopenic elders. METHODS: The study was a randomized controlled trial using a parallel-group design. Each group received two therapeutic periods lasted 12 weeks with an interval of 2 weeks in between. Physical performance and body composition were assessed at baseline and immediately following the end of the first and second phases. One phase included hospital-based resistance training and nutritional support (amino acid, calcium, and vitamin D3), whereas the other phase included home-based exercise. In the early intervention group, supervised exercise and nutrition supplementation were administered first followed by home-based exercise, whereas the sequence was reversed in the delayed intervention group. The influence of intervention sequence on the outcome variables was examined using a 3∗2 repeated-measures analysis of variance. The primary endpoints were defined as changes in lean mass and related physical function (grip strength and gait speed) over 12 and 26 weeks of interventions. RESULTS: A total of 57 sarcopenic elders were randomly assigned to the early (n = 29) and delayed (n = 28) intervention groups. Among the primary endpoints, the only significant group-time interaction was recognized on the changes of lower extremity lean mass (p = 0.039). The early intervention was associated with an earlier increase in lower extremity lean mass (770.8 g, 95% confidence interval (CI), 564.8 g-976.9 g) than delayed intervention (294.2 g, 95% CI, -42.13 to 630.5 g) which was evident from the between-group comparison between baseline and the 1st follow-up (p = 0.016). No significant effect of group-time interaction was observed on the physical performance and other components of body composition. CONCLUSIONS: Early exercise and nutritional intervention may be helpful in an earlier restoration of lower extremity muscle mass but not physical function in sarcopenic elders. When designing a rehabilitation program for patients with sarcopenia, resistance training with nutrition support can be prescribed first for the rapid enlargement of the muscle volume, and structuralized home-based exercise can be administered subsequently to preserve the prior intervention effect. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02779088).

Expression of Telomeric Repeat-Containing RNA Decreases in Sarcopenia and Increases after Exercise and Nutrition Intervention.

Sarcopenia is defined as aging-related loss of muscle mass and function. Telomere length in chromosomes shortens with age and is modulated by telomeric repeat-containing RNA (TERRA). This study aimed to explore the impact of aging and sarcopenia on telomere length and TERRA expression, and changes following strengthening exercise and nutrition intervention (supplement of branched-chain amino acids, calcium and vitamin D3) for 12 weeks in the sarcopenic population. Older adults (≥65 years old) were divided into non-sarcopenic controls (n = 36) and sarcopenic individuals (n = 36) after measurement of grip strength and body composition. The relative telomere length of leukocytes in all research participants was evaluated using the T/S ratio (telomere/single copy gene), and relative TERRA expression of leukocytes was determined by reverse-transcription qPCR (RT-qPCR). Generalized estimating equation (GEE) was used to analyze the influence of sarcopenia and intervention on the outcomes. There was no significant difference in telomere length between control subjects and participants with sarcopenia. TERRA expression was lower in sarcopenic participants compared to that in non-sarcopenic controls (5.18 ± 2.98 vs. 2.51 ± 1.89; p < 0.001). In the sarcopenic group, intervention significantly increased TERRA expression, but not telomere length. The GEE analysis demonstrated that TERRA expression was negatively associated with sarcopenia (ß coefficient = -2.705, p < 0.001) but positively associated with intervention (ß coefficient = 1.599, p = 0.023). Sarcopenia is associated with a decrease in TERRA expression in leukocytes. Rebound TERRA expression (returning to the level similar to the non-sarcopenic controls) was observed in the sarcopenic group after exercise and nutrition intervention. Future studies are warranted to examine the potential of TERRA as a biomarker for sarcopenia and its subsequent responses to intervention.

Comparative Effectiveness of Botulinum Toxin Injection for Chronic Shoulder Pain: A Meta-Analysis of Randomized Controlled Trials.

Botulinum toxin (BoNT) injection is regarded as a promising treatment for musculoskeletal pain. However, its efficacy for treating chronic shoulder pain remains unclear. We investigated the effectiveness of BoNT injections for chronic shoulder pain by conducting a systematic search of electronic databases up to March 2020 for randomized control trials (RCTs) that used BoNT injections for chronic shoulder pain treatment. The primary outcome was the between-group comparison of pain reduction, quantified by the standardized mean difference (SMD). Nine RCTs comprising 666 patients were included and divided into two groups: one group with shoulder joint pain (n = 182) and the other group with shoulder myofascial pain (n = 484). Regarding shoulder joint pain, the efficacy of BoNT injections was similar to that of the reference treatment (SMD: -0.605, 95% confidence level [CI]: -1.242 to 0.032 versus saline; SMD: -0.180, 95% CI: -0.514 to 0.153 versus corticosteroids) at one month post-intervention, and was superior (SMD: -0.648, 95% CI: -0.1071 to -0.225 versus corticosteroids) between one and three months. Likewise, in terms of shoulder myofascial pain, the effectiveness of BoNT injections did not differ from the reference treatment (SMD: -0.212, 95% CI: -0.551 to 0.127 versus saline; SMD: 0.665, 95% CI: -0.260 to 1.590 versus dry needling and SMD: 1.093; 95% CI: 0.128 to 2.058 versus lidocaine) at one month post- intervention, and appeared superior (SMD: -0.314, 95% CI: -0.516 to -0.111 versus saline) between one and three months. Our meta-analysis revealed that BoNT injections could be a safe and effective alternative for patients with chronic shoulder pain.

Involvement of Substance P in the Analgesic Effect of Low-Level Laser Therapy in a Mouse Model of Chronic Widespread Muscle Pain.

BACKGROUND: Low-level laser therapy (LLLT) is widely used in pain control in the field of physical medicine and rehabilitation and is effective for fibromyalgia pain. However, its analgesic mechanism remains unknown. A possible mechanism for the effect of LLLT on fibromyalgia pain is via the antinociceptive signaling of substance P in muscle nociceptors, although the neuropeptide has been known as a neurotransmitter to facilitate pain signals in the spinal cord. OBJECTIVE: To establish an animal model of LLLT in chronic muscle pain and to determine the role of substance P in LLLT analgesia. METHODS: We employed the acid-induced chronic muscle pain model, a fibromyalgia model proposed and developed by Sluka et al., and determined the optimal LLLT dosage. RESULTS: LLLT with 685 nm at 8 J/cm2 was effective to reduce mechanical hyperalgesia in the chronic muscle pain model. The analgesic effect was abolished by pretreatment of NK1 receptor antagonist RP-67580. Likewise, LLLT showed no analgesic effect on Tac1-/- mice, in which the gene encoding substance P was deleted. Besides, pretreatment with the TRPV1 receptor antagonist capsazepine, but not the ASIC3 antagonist APETx2, blocked the LLLT analgesic effect. CONCLUSIONS: LLLT analgesia is mediated by the antinociceptive signaling of intramuscular substance P and is associated with TRPV1 activation in a mouse model of fibromyalgia or chronic muscle pain. The study results could provide new insight regarding the effect of LLLT in other types of chronic pain.

Comparative effectiveness of dextrose prolotherapy versus control injections and exercise in the management of osteoarthritis pain: a systematic review and meta-analysis.

BACKGROUND: Increasing evidence has supported the use of dextrose prolotherapy for patients with osteoarthritis. However, the real benefits may be affected by differences in injection protocols, comparative regimens, and evaluation scales. METHODS: PubMed and Scopus were searched from the earliest record until February 2016. One single-arm study and five randomized controlled trials were included, comprising 326 participants. We estimated the effect sizes of pain reduction before and after serial dextrose injections and compared the values between dextrose prolotherapy, comparative regimens, and exercise 6 months after the initial injection. RESULTS: Regarding the treatment arm using dextrose prolotherapy, the effect sizes compared with baseline were 0.65 (95% confidence interval [CI], 0.14-1.17), 0.84 (95% CI, 0.40-1.27), 0.85 (95% CI, 0.60-1.10), and 0.87 (95% CI, 0.53-1.21) after the first, second, third, and fourth or more injections, respectively. The overall effect of dextrose was better than control injections (effect size, 0.36; 95% CI, 0.10-0.63). Dextrose prolotherapy had a superior effect compared with local anesthesia (effect size, 0.38; 95% CI, 0.07-0.70) and exercise (effect size, 0.71; 95% CI, 0.30-1.11). There was an insignificant advantage of dextrose over corticosteroids (effect size, 0.31; 95% CI, -0.18 to 0.80) which was only estimated from one study. CONCLUSION: Dextrose injections decreased pain in osteoarthritis patients but did not exhibit a positive dose-response relationship following serial injections. Dextrose prolotherapy was found to provide a better therapeutic effect than exercise, local anesthetics, and probably corticosteroids when patients were retested 6 months following the initial injection.