Massage as a Mechanotherapy for Skeletal Muscle.

Massage is anecdotally associated with many health benefits, but physiological and clinically relevant mechanisms recently have begun to be investigated in a controlled manner. Herein, we describe research supporting our hypothesis that massage can be used as a mechanotherapy imparting biologically relevant adaptations in skeletal muscle and improving muscle properties.

Breast Implant-associated Anaplastic Large Cell Lymphoma: An Evidence-based Systematic Review.

OBJECTIVE: This evidence-based systematic review synthesizes and critically appraises current clinical recommendations and advances in the diagnosis and treatment of BIA-ALCL. This review also aims to broaden physician awareness across diverse specialties, particularly among general practitioners, breast surgeons, surgical oncologists, and other clinicians who may encounter patients with breast implants in their practice. BACKGROUND: BIA-ALCL is an emerging and treatable immune cell cancer definitively linked to textured-surface breast implants. Although the National Comprehensive Cancer Network (NCCN) consensus guidelines and other clinical recommendations have been established, the evidence supporting these guidelines has not been systematically studied. The purpose of this evidence-based systematic review is to synthesize and critically appraise current clinical guidelines and recommendations while highlighting advances in diagnosis and treatment and raising awareness for this emerging disease. METHODS: This evidence-based systematic review evaluated primary research studies focusing on the diagnosis and treatment of BIA-ALCL that were published in PubMed, Google Scholar, and other scientific databases through March 2020. RESULTS AND CONCLUSIONS: The clinical knowledge of BIA-ALCL has evolved rapidly over the last several years with major advances in diagnosis and treatment, including en bloc resection as the standard of care. Despite a limited number of high-quality clinical studies comprised mainly of Level III and Level V evidence, current evidence aligns with established NCCN consensus guidelines. When diagnosed and treated in accordance with NCCN guidelines, BIA-ALCL carries an excellent prognosis.

Massage as a mechanotherapy promotes skeletal muscle protein and ribosomal turnover but does not mitigate muscle atrophy during disuse in adult rats.

AIM: Interventions that decrease atrophy during disuse are desperately needed to maintain muscle mass. We recently found that massage as a mechanotherapy can improve muscle regrowth following disuse atrophy. Therefore, we aimed to determine if massage has similar anabolic effects when applied during normal weight bearing conditions (WB) or during atrophy induced by hindlimb suspension (HS) in adult rats. METHODS: Adult (10 months) male Fischer344-Brown Norway rats underwent either hindlimb suspension (HS, n = 8) or normal WB (WB, n = 8) for 7 days. Massage was applied using cyclic compressive loading (CCL) in WB (WBM, n = 9) or HS rats (HSM, n = 9) and included four 30-minute bouts of CCL applied to gastrocnemius muscle every other day. RESULTS: Massage had no effect on any anabolic parameter measured under WB conditions (WBM). In contrast, massage during HS (HSM) stimulated protein turnover, but did not mitigate muscle atrophy. Atrophy from HS was caused by both lowered protein synthesis and higher degradation. HS and HSM had lowered total RNA compared with WB and this was the result of significantly higher ribosome degradation in HS that was attenuated in HSM, without differences in ribosomal biogenesis. Also, massage increased protein turnover in the non-massaged contralateral limb during HS. Finally, we determined that total RNA degradation primarily dictates loss of muscle ribosomal content during disuse atrophy. CONCLUSION: We conclude that massage is an effective mechanotherapy to impact protein turnover during muscle disuse in both the massaged and non-massaged contralateral muscle, but it does not attenuate the loss of muscle mass.

Massage increases satellite cell number independent of the age-associated alterations in sarcolemma permeability.

Massage is a widely accepted manual therapy used to modulate the inflammatory response of muscle and restore function, but prolonged compression of muscle potentially causes overt injury and damage to muscle fibers. Therefore, a balance exists between the positive effects of massage and the induction of mechanical damage and injury. In addition, skeletal muscle of aged individuals displays increased stiffness, and therefore, the response to massage is likely different compared with young. We hypothesized that the aged skeletal muscle exhibits increased sarcolemmal permeability when subjected to massage compared with young skeletal muscle. Male Brown Norway/F344 rats, 10 and 30 months of age, were each divided into control, non-massaged (n = 8) and massaged (n = 8) groups. The right gastrocnemius muscle received one bout of cyclic compressive loading for 30 min at 4.5 N as a massage-mimetic. Muscles were dissected and frozen 24 h after massage. Alterations in sarcolemma permeability were quantified by measuring the level of intracellular IgG within the muscle fibers. Immunohistochemistry was performed to determine IgG inside fibers and Pax7+ cell number as an indicator of stem cell abundance. Average IgG intensity was not different between control and massaged animals at either age. However, a significant shift to the right of the density histogram indicated that massaged animals had more fibers with higher IgG intensity than control at 10 months. In addition, Pax7+ cell number was significantly elevated in massaged muscles compared with control at both ages. One bout of massage did not induce overt muscle injury, but facilitated membrane permeability, which was associated with an increase in satellite cell number. Data suggest that the load applied here, which was previously shown to induce immunomodulatory changes, does not induce overt muscle injury in young and old muscles but may result in muscle remodeling. Funded by NIH grant AG042699 and AT009268.

Enhanced skeletal muscle regrowth and remodelling in massaged and contralateral non-massaged hindlimb.

KEY POINTS: Muscle fibre cross sectional area is enhanced with massage in the form of cyclic compressive loading during regrowth after atrophy. Massage enhances protein synthesis of the myofibrillar and cytosolic, but not the mitochondrial fraction, in muscle during regrowth. Focal adhesion kinase activation and satellite cell number are elevated in muscles undergoing massage during regrowth. Muscle fibre cross sectional area and protein synthesis of the myofibrillar fraction, but not DNA synthesis, are elevated in muscle of the contralateral non-massaged limb. Massage in the form of cyclic compressive loading is a potential anabolic intervention during muscle regrowth after atrophy. ABSTRACT: Massage, in the form of cyclic compressive loading (CCL), is associated with multiple health benefits, but its potential anabolic effect on atrophied muscle has not been investigated. We hypothesized that the mechanical activity associated with CCL induces an anabolic effect in skeletal muscle undergoing regrowth after a period of atrophy. Fischer-Brown Norway rats at 10 months of age were hindlimb unloaded for a period of 2 weeks. The rats were then allowed reambulation with CCL applied at a 4.5 N load at 0.5 Hz frequency for 30 min every other day for four bouts during a regrowth period of 8 days. Muscle fibre cross sectional area was enhanced by 18% with massage during regrowth compared to reloading alone, and this was accompanied by elevated myofibrillar and cytosolic protein as well as DNA synthesis. Focal adhesion kinase phosphorylation indicated that CCL increased mechanical stimulation, while a higher number of Pax7+ cells likely explains the elevated DNA synthesis. Surprisingly, the contralateral non-massaged limb exhibited a comparable 17% higher muscle fibre size compared to reloading alone, and myofibrillar protein synthesis, but not DNA synthesis, was also elevated. We conclude that massage in the form of CCL induces an anabolic response in muscles regrowing after an atrophy-inducing event. We suggest that massage can be used as an intervention to aid in the regrowth of muscle lost during immobilization.

Effects of immediate vs. delayed massage-like loading on skeletal muscle viscoelastic properties following eccentric exercise.

BACKGROUND: This study compared immediate versus delayed massage-like compressive loading on skeletal muscle viscoelastic properties following eccentric exercise. METHODS: Eighteen rabbits were surgically instrumented with peroneal nerve cuffs for stimulation of the tibialis anterior muscle. Rabbits were randomly assigned to a massage loading protocol applied immediately post exercise (n=6), commencing 48h post exercise (n=6), or exercised no-massage control (n=6). Viscoelastic properties were evaluated in vivo by performing a stress-relaxation test pre- and post-exercise and daily pre- and post-massage for four consecutive days of massage loading. A quasi-linear viscoelastic approach modeled the instantaneous elastic response (AG0), fast (g1(p)) and slow (g2(p)) relaxation coefficients, and the corresponding relaxation time constants τ1 and τ2. FINDINGS: Exercise increased AG0 in all groups (P<0.05). After adjusting for the three multiple comparisons, recovery of AG0 was not significant in the immediate (P=0.021) or delayed (P=0.048) group compared to the control group following four days of massage. However, within-day (pre- to post-massage) analysis revealed a decrease in AG0 in both massage groups. Following exercise, g1(p) increased and g2(p) and τ1 decreased for all groups (P<0.05). Exercise had no effect on τ2 (P>0.05). After four days of massage, there was no significant recovery of the relaxation parameters for either massage loading group compared to the control group. INTERPRETATION: Our findings suggest that massage loading following eccentric exercise has a greater effect on reducing muscle stiffness, estimated by AG0, within-day rather than affecting recovery over multiple days. Massage loading also has little effect on the relaxation response.

Investigating the mechanisms of massage efficacy: the role of mechanical immunomodulation.

Massage has the potential to attenuate the inflammatory process, facilitate early recovery, and provide pain relief from muscular injuries. In this hypothesis-driven paper, we integrate the concept of mechanotransduction with the application of massage to explore beneficial mechanisms. By altering signaling pathways involved with the inflammatory process, massage may decrease secondary injury, nerve sensitization, and collateral sprouting, resulting in increased recovery from damage and reduction or prevention of pain. Our goal is to provide a framework that describes our current understanding of the mechanisms whereby massage therapy activates potentially beneficial immunomodulatory pathways.

Immunomodulatory effects of massage on nonperturbed skeletal muscle in rats.

Massage is an ancient manual therapy widely utilized by individuals seeking relief from various musculoskeletal maladies. Despite its popularity, the majority of evidence associated with massage benefits is anecdotal. Recent investigations have uncovered physiological evidence supporting its beneficial use following muscle injury; however, the effects of massage on healthy, unperturbed skeletal muscle are unknown. Utilizing a custom-fabricated massage mimetic device, the purpose of this investigation was to elucidate the effects of various loading magnitudes on healthy skeletal muscle with particular interest in the gene expression profile and modulation of key immune cells involved in the inflammatory response. Twenty-four male Wistar rats (200 g) were subjected to cyclic compressive loading (CCL) over the right tibialis anterior muscle for 30 min, once a day, for 4 consecutive days using four loading conditions: control (0N), low load (1.4N), moderate load (4.5N), and high load (11N). Microarray analysis showed that genes involved with the immune response were the most significantly affected by application of CCL. Load-dependent changes in cellular abundance were seen in the CCL limb for CD68(+) cells, CD163(+) cells, and CD43(+)cells. Surprisingly, load-independent changes were also discovered in the non-CCL contralateral limb, suggesting a systemic response. These results show that massage in the form of CCL exerts an immunomodulatory response to uninjured skeletal muscle, which is dependent upon the applied load.

Massage timing affects postexercise muscle recovery and inflammation in a rabbit model.

PURPOSE: This study compared the effect of immediate versus delayed massage-like compressive loading (MLL) on peak isometric torque recovery and inflammatory cell infiltration after eccentric exercise (EEX). METHODS: Eighteen skeletally mature New Zealand White rabbits were instrumented with peroneal nerve cuffs for the stimulation of hindlimb tibialis anterior muscles. After a bout of EEX, rabbits were randomly assigned to an MLL protocol (0.5 Hz, 10 N, 15 min) that started immediately post-EEX, 48 h post-EXX, or no-MLL control and performed for four consecutive days. A torque-angle (T-Θ) relationship was obtained for 21 joint angles pre- and post-EEX and after four consecutive days of MLL or no-MLL. Muscle wet weights and immunohistochemical sections were obtained after final treatments. RESULTS: EEX produced an average 51% ± 13% decrease in peak isometric torque output. The greatest peak torque recovery occurred with the immediate application of MLL. There were differences in torque recovery between immediate and delayed MLL (P = 0.0012), immediate MLL and control (P < 0.0001), and delayed MLL and control (P = 0.025). Immunohistochemical analysis showed 39.3% and 366.0% differences in the number of RPN3/57 and CD11b-positive cells between immediate (P = 0.71) and delayed MLL (P = 0.12). The area under the T-Θ curve showed a difference for immediate (P < 0.0001) and delayed (P = 0.0051) MLL as compared with control. Exercise produced an average 10° ± 0.2° rightward shift from preexercise peak isometric torque angle. Control, immediate MLL, and delayed MLL produced an average leftward angular shift from the postexercise angle (P = 0.28, P = 0.03, and P = 0.47, respectively). CONCLUSION: Post-EEX, immediate MLL was more beneficial than delayed MLL in restoring muscle function and in modulating inflammatory cell infiltration. These findings invite similar human studies to make definitive conclusions on optimal timing of massage-based therapies.

Dose-dependency of massage-like compressive loading on recovery of active muscle properties following eccentric exercise: rabbit study with clinical relevance.

BACKGROUND: Optimal strategies for massage and its use in athletes have not been conclusively demonstrated. PURPOSE/STUDY DESIGN: Effects of varying duration, frequency and magnitude of massage-like compressive loading (MLL) on recovery of skeletal muscle active properties (torque angle (T-Θ) relationship) following exercise-induced muscle injury were studied. METHODS: Twenty-four New Zealand White rabbits were surgically instrumented with bilateral peroneal nerve cuffs for stimulation of hindlimb tibialis anterior muscles. Following a bout of eccentric exercise (EEX), rabbits were randomly assigned to a MLL protocol of 0.25 or 0.5 Hz at 5 or 10 N for 15 or 30 min. T-Θ was obtained for 21 tibiotarsal joint angles pre- and post-EEX and post 4 consecutive days of MLL. Muscle wet weight and H&E sections were obtained following final treatments. RESULTS: EEX produced an average 61.8%±2.1 decrease in peak isometric torque output. Differences in torque recovery were found between magnitudes (5 and 10 N; p=0.004, n=12) and frequencies (0.25 and 0.5 Hz; p=0.012, n=12), but no difference for durations (15 and 30 min) with the 0.5 Hz, 10 N, 15 min protocol showing greatest recovery 4 days post-EEX. MLL muscle (n=12) wet weight was 3.22±0.18 g, while no MLL tissue (n=9) weighed 3.74±0.22 g (p=0.029). Histological analysis showed a difference in torn fibres between low-parameter and high-parameter MLL (6.5±1.04 vs 0.5±0.29 per 0.59 mm(2), p=0.005). CONCLUSIONS: Results showed a dose-response effect for magnitude and frequency of MLL on recovery of active muscle properties following EEX. Future studies will investigate underlying biological mechanisms for this enhanced recovery of muscle function.

In vivo passive mechanical properties of skeletal muscle improve with massage-like loading following eccentric exercise.

A quasi-linear viscoelasticity (QLV) model was used to study passive time-dependent responses of skeletal muscle to repeated massage-like compressive loading (MLL) following damaging eccentric exercise. Six skeletally mature rabbits were surgically instrumented with bilateral peroneal nerve cuffs for stimulation of the hindlimb tibialis anterior (TA) muscles. Following the eccentric exercise, rabbits were randomly assigned to a four-day MLL protocol mimicking deep effleurage (0.5 Hz, 10 N for 15 min or for 30 min). The contralateral hindlimb served as the exercised, no-MLL control for both MLL conditions. Viscoelastic properties of the muscle pre-exercise, post-exercise on Day 1, and pre- and post-MLL Day 1 through Day 4 were determined with ramp-and-hold tests. The instantaneous elastic response (AG(0)) increased following exercise (p<0.05) and decreased due to both the 15 min and 30 min four-day MLL protocols (p<0.05). Post-four days of MLL the normalized AG(0) decreased from post-exercise (Day 1, 248.5%) to the post-MLL (Day 4, 98.5%) (p<0.05), compared to the no-MLL group (Day 4, 222.0%) (p<0.05). Exercise and four-day MLL showed no acute or cumulative effects on the fast and slow relaxation coefficients (p>0.05). This is the first experimental evidence of the effect of both acute (daily) and cumulative changes in viscoelastic properties of intensely exercised muscle due to ex vivo MLL. It provides a starting point for correlating passive muscle properties with mechanical effects of manual therapies, and may shed light on design and optimization of massage protocols.

Cyclic compressive loading facilitates recovery after eccentric exercise.

PURPOSE: To assess the biologic basis of massage therapies, we developed an experimental approach to mimic Swedish massage and evaluate this approach on recovery from eccentric exercise-induced muscle damage using a well-controlled animal model. METHODS: Tibialis anterior muscles of six New Zealand White rabbits were subjected to one bout of damaging, eccentric contractions. One muscle was immediately subjected to cyclic compressive loads, and the contralateral served as the exercised control. RESULTS: We found that commencing 30 min of cyclic compressive loading to the muscle, immediately after a bout of eccentric exercise, facilitated recovery of function and attenuated leukocyte infiltration. In addition, fiber necrosis and wet weight of the tissue were also reduced by compressive loading. CONCLUSION: We conclude that subjecting muscle to compressive loads immediately after exercise leads to an enhanced recovery of muscle function and attenuation of the damaging effects of inflammation in the rabbit model. Although these observations suggest that skeletal muscle responds to cyclic compressive forces similar to those generated by clinical approaches, such as therapeutic massage, further research is needed to assess the translational efficacy of these findings.