Influence of topical menthol gel on thermoregulation and perception while walking in the heat.

PURPOSE: Menthol is known to elicit opposing thermoregulatory and perceptual alterations during intense exercise. The current purpose was to determine the thermoregulatory and perceptual effects of topical menthol application prior to walking in the heat. METHODS: Twelve participants walked (1.6 m s-1, 5% grade) for 30 min in the heat (38 °C, 60% relative humidity) with either a 4% menthol or control gel on the upper (shoulder to wrist) and lower (mid-thigh to ankle) limbs. Skin blood flow (SkBF), sweat (rate, composition), skin conductivity, heart rate, temperature (skin, core), and thermal perception were measured prior to and during exercise. RESULTS: Skin conductivity expressed as time to 10, 20, 30, and 40 µS was delayed due to menthol (559 ± 251, 770 ± 292, 1109 ± 301, 1299 ± 335 s, respectively) compared to the control (515 ± 260, 735 ± 256, 935 ± 300, 1148 ± 298 s, respectively, p = 0.048). Sweat rate relative to body surface area was lower due to menthol (0.55 ± 0.16 L h-1 m(2)-1) than the control (0.64 ± 0.16 L h-1 m(2)-1, p = 0.049). Core temperature did not differ at baseline between the menthol (37.4 ± 0.3 °C) and control (37.3 ± 0.4 °C, p = 0.298) but was higher at 10, 20, and 30 min due to menthol (37.5 ± 0.3, 37.7 ± 0.2, 38.1 ± 0.3 °C, respectively) compared to the control (37.3 ± 0.4, 37.4 ± 0.3, 37.7 ± 0.3 °C, respectively, p < 0.05). The largest rise in core temperature from baseline was at 30 min during menthol (0.7 ± 0.3 °C) compared to the control (0.4 ± 0.2 °C, p = 0.004). Overall, the menthol treatment was perceived cooler, reaching "slightly warm" whereas the control treatment reached "warm" (p < 0.001). CONCLUSION: Menthol application to the limbs impairs whole-body thermoregulation while walking in the heat despite perceiving the environment as cooler.

The isolated effects of local cold application on proteolytic and myogenic signaling.

Post-exercise cooling studies reveal inhibitory effects on markers of skeletal muscle growth. However, the isolated effect of local cold application has not been adequately addressed. It is unclear if the local cold or the combination of local cold and exercise is driving negatively altered skeletal muscle gene expression. The purpose was to determine the effects of a 4 h local cold application to the vastus lateralis on the myogenic and proteolytic response. Participants (n = 12, 27 ± 6 years, 179 ± 9 cm, 82.8 ± 13.0 kg, 18.4 ± 7.1 %BF) rested with a thermal wrap placed on each leg with either circulating cold fluid (10 °C, COLD) or no fluid circulation (room temperature, RT). Muscle samples were collected to quantify mRNA (RT-qPCR) and proteins (Western Blot) associated with myogenesis and proteolysis. Temperatures in COLD were lower than RT at the skin (13.2 ± 1.0 °C vs. 34.8 ± 0.9 °C; p < 0.001) and intramuscularly (20.5 ± 1.3 °C vs. 35.6 ± 0.8 °C, p < 0.001). Myogenic-related mRNA, MYO-G and MYO-D1, were lower in COLD (p = 0.001, p < 0.001, respectively) whereas myogenic-mRNA, MYF6, was greater in COLD (p = 0.002). No other myogenic associated genes were different between COLD and RT (MSTN, p = 0.643; MEF2a, p = 0.424; MYF5, p = 0.523; RPS3, p = 0.589; RPL3-L, p = 0.688). Proteolytic-related mRNA was higher in COLD (FOXO3a, p < 0.001; Atrogin-1, p = 0.049; MURF-1, p < 0.001). The phosphorylation:total protein ratio for the translational repressor of muscle mass, 4E-BP1Thr37/46, was lower in COLD (p = 0.043), with no differences in mTORser2448 (p = 0.509) or p70S6K1Thr389 (p = 0.579). Isolated local cooling over 4 h exhibits inhibited myogenic and higher proteolytic skeletal muscle molecular response.

The independent effects of local heat application on muscle growth program associated mRNA and protein phosphorylation.

The development and maintenance of skeletal muscle is crucial for the support of daily function. Recent evidence suggests that genes coded for proteins associated with the human muscle growth program (myogenic and proteolytic genes) are sensitive to local heat application. Therefore, the purpose of this investigation was to determine the effect of 4 h of local heat application to the vastus lateralis at rest on acute phosphorylation (mTORSer2448, p70-S6K1Thr389, and 4E-BP1Thr47/36) and gene expression changes for proteins associated with the muscle growth program. Intramuscular temperature of the HOT limb was 1.2 ± 0.2 °C higher than CON limb after 4 h of local heating. However, this local heat stimulus did not influence transcription of genes associated with myogenesis (MSTN, p = 0.321; MYF5, p = 0.445; MYF6, p = 0.895; MEF2a, p = 0.809; MYO-G, p = 0.766; MYO-D1, p = 0.118; RPS3, p = 0.321; and RPL-3L, p = 0.577), proteolysis (Atrogin-1, p = 0.573; FOXO3a, p = 0.452; MURF-1, p = 0.284), nor protein phosphorylation (mTORSer2448, p = 0.981; P70-S6K1Thr389, p = 0.583; 4E-BP1Thr37/46, p = 0.238) associated with the muscle growth program. These findings suggest little to no association between the local application of heat, at rest, and the activation of the observed muscle growth program-related markers.

Influence of topical capsaicin cream on thermoregulation and perception during acute exercise in the heat.

PURPOSE: Determine if topical capsaicin, a transient receptor potential vanilloid heat thermoreceptor activator, alters thermoregulation and perception when applied topically prior to thermal exercise. METHODS: Twelve subjects completed 2 treatments. Subjects walked (1.6 m s-1, 5% grade) for 30 min in the heat (38 °C, 60% relative humidity) with either a capsaicin (0.025% capsaicin) or control cream applied to the upper (shoulder to wrist) and lower (mid-thigh to ankle) limbs covering ∼50% body surface area. Skin blood flow (SkBF), sweat (rate, composition), heart rate, temperature (skin, core), and perceived thermal sensation were measured prior to and during exercise. RESULTS: The relative change in SkBF was not different between treatments at any time point (p = 0.284). There were no differences in sweat rate between the capsaicin (1.23 ± 0.37 L h-1) and control (1.43 ± 0.43 L h-1, p = 0.122). There were no differences in heart rate between the capsaicin (122 ± 38 beats·min-1) and control (125 ± 39 beats·min-1, p = 0.431). There were also no differences in weighted surface (p = 0.976) or body temperatures (p = 0.855) between the capsaicin (36.0 ± 1.7 °C, 37.0 ± 0.8 °C, respectively) and control (36.0 ± 1.6 °C, 36.9 ± 0.8 °C, respectively). The capsaicin treatment was not perceived as hotter than the control treatment until minute 30 of exercise (2.8 ± 0.4, 2.5 ± 0.5, respectively, p = 0.038) CONCLUSIONS: Topical capsaicin application does not alter whole-body thermoregulation during acute exercise in the heat despite perceiving the treatment as hotter late in exercise.

No Mitochondrial Related Transcriptional Changes in Human Skeletal Muscle after Local Heat Application.

The purpose of the study is to determine the impact of local heating on skeletal muscle transcriptional response related to mitochondrial biogenesis and mitophagy. Twelve healthy subjects (height, 176.0 ± 11.9 cm; weight, 83.6 ± 18.3 kg; and body composition, 19.0 ± 7.7% body fat) rested in a semi-reclined position for 4 h with a heated thermal wrap (HOT) around one thigh and a wrap without temperature regulation (CON) around the other (randomized). Skin temperature, blood flow, intramuscular temperature, and a skeletal muscle biopsy from the vastus lateralis were obtained after the 4 h intervention. Skin temperature via infrared thermometer and thermal camera was higher after HOT (37.3 ± 0.7 and 36.7 ± 1.0 °C, respectively) than CON (34.8 ± 0.7, 35.2 ± 0.8 °C, respectively, p < 0.001). Intramuscular temperature was higher in HOT (36.3 ± 0.4 °C) than CON (35.2 ± 0.8 °C, p < 0.001). Femoral artery blood flow was higher in HOT (304.5 ± 12.5 mL‧min-1) than CON (272.3 ± 14.3 mL‧min-1, p = 0.003). Mean femoral shear rate was higher in HOT (455.8 ± 25.1 s-1) than CON (405.2 ± 15.8 s-1, p = 0.019). However, there were no differences in any of the investigated genes related to mitochondrial biogenesis (PGC-1α, NRF1, GAPBA, ERRα, TFAM, VEGF) or mitophagy (PINK-1, PARK-2, BNIP-3, BNIP-3L) in response to heat (p > 0.05). These data indicate that heat application alone does not impact the transcriptional response related to mitochondrial homeostasis, suggesting that other factors, in combination with skeletal muscle temperature, are involved with previous observations of altered exercise induced gene expression with heat.

Influence of Local Muscle Cooling on Mitochondrial-Related Gene Expression at Rest.

The purpose of this study was to determine the impact of localized cooling of the skeletal muscle during rest on mitochondrial related gene expression. Thermal wraps were applied to the vastus lateralis of each limb of 12 participants. One limb received a cold application (randomized) (COLD), while the other did not (RT). Wraps were removed at the 4 h time point and measurements of skin temperature, blood flow, and intramuscular temperature were taken prior to a muscle biopsy. RT-qPCR was used to measure expression of genes associated with mitochondrial development. Skin and muscle temperatures were lower in COLD than RT (p < 0.05). Femoral artery diameter was lower in COLD after 4 h (0.62 ± 0.05 cm, to 0.60 ± 0.05 cm, p = 0.018). Blood flow was not different in COLD compared to RT (259 ± 69 mL·min-1 vs. 275 ± 54 mL·min-1, p = 0.20). PGC-1α B and GABPA expression was higher in COLD relative to RT (1.57-fold, p = 0.037 and 1.34-fold, p = 0.006, respectively). There was no difference (p > 0.05) in the expression of PGC-1α, NT-PGC-1α, PGC-1α A, TFAM, ESRRα, NRF1, GABPA, VEGF, PINK1, PARK 2, or BNIP3-L. The impact of this small magnitude of difference in gene expression of PGC-1α B and GABPA without alterations in other genes are unknown. There appears to be only limited impact of local muscle cooling on the transcriptional response related to mitochondrial development.

Heat Acclimation in Females Does Not Limit Aerobic Exercise Training Outcomes.

Recent aerobic exercise training in the heat has reported blunted aerobic power improvements and reduced mitochondrial-related gene expression in men. It is unclear if this heat-induced blunting of the training response exists in females. The purpose of the present study was to determine the impact of 60 min of cycling in the heat over three weeks on thermoregulation, gene expression, and aerobic capacity in females. Untrained females (n = 22; 24 ± 4yoa) were assigned to three weeks of aerobic training in either 20 °C (n = 12) or 33 °C (n = 10; 40%RH). Maximal aerobic capacity (39.5 ± 6.5 to 41.5 ± 6.2 mL·kg−1·min−1, p = 0.021, ηp2 = 0.240, 95% CI [0.315, 3.388]) and peak aerobic power (191.0 ± 33.0 to 206.7 ± 27.2 W, p < 0.001, ηp2 = 0.531, 95% CI [8.734, 22.383]) increased, while the absolute-intensity trial (50%VO2peak) HR decreased (152 ± 15 to 140 ± 13 b·min−1, p < 0.001, ηp2 = 0.691, 95% CI [15.925, 8.353]), but they were not different between temperatures (p = 0.440, p = 0.955, p = 0.341, respectively). Independent of temperature, Day 22 tolerance trial skin temperatures decreased from Day 1 (p = 0.006, ηp2 = 0.319, 95% CI [1.408, 0.266), but training did not influence core temperature (p = 0.598). Average sweat rates were higher in the 33 °C group vs. the 20 °C group (p = 0.008, ηp2 = 0.303, 95% CI [67.9, 394.9]) but did not change due to training (p = 0.571). Pre-training PGC-1α mRNA increased 4h-post-exercise (5.29 ± 0.70 fold change, p < 0.001), was lower post-training (2.69 ± 0.22 fold change, p = 0.004), and was not different between temperatures (p = 0.455). While training induced some diminished transcriptional stimulus, generally the training temperature had little effect on genes related to mitochondrial biogenesis, mitophagy, and metabolic enzymes. These female participants increased aerobic fitness and maintained an exercise-induced PGC-1α mRNA response in the heat equal to that of room temperature conditions, contrasting with the blunted responses previously observed in men.

Effect of local heat application during exercise on gene expression related to mitochondrial homeostasis.

The aim of this study was to determine the impact of local muscle heating during endurance exercise on human skeletal muscle mitochondrial-related gene expression. Twelve subjects (25 ± 6 yr, 177 ± 8 cm, 78 ± 16 kg, and peak aerobic capacity 45 ± 8 mL·kg-1·min-1) cycled with one leg heated (HOT) and the other serving as a control (CON). Skin and intramuscular temperatures were taken before temperature intervention (Pre), after 30 minutes (Pre30), after exercise (Post) and four hours after exercise (4Post). Muscle biopsies were taken from each leg at Pre and 4Post. Intramuscular temperature increased within HOT (34.4 ± 0.7 °C to 36.1 ± 0.5 °C, p < 0.001) and was higher than CON at Pre30 (34.0 ± 0.7 °C, p < 0.001). However, temperatures at POST were similar (HOT 38.4 ± 0.7 °C, CON 38.3 ± 0.5 °C, p = 0.661). Skin temperature was higher than CON at Post30 (30.3 ± 1.0 °C, p < 0.001) and Post (HOT 34.6 ± 0.9 °C, CON 32.3 ± 1.6 °C, p < 0.001). PGC-1α, VEGF and NRF2 mRNA increased with exercise (p < 0.05) but was not altered with heating (p > 0.05). TFAM increased after exercise with heat application (HOT, p = 0.019) but not with exercise alone (CON, p = 0.422). There was no difference in NRF1, ESRRα, or any of the mitophagy related genes in response to exercise or temperature (p > 0.05). In conclusion, TFAM is enhanced by local heat application during endurance exercise, whereas other genes related to mitochondrial homeostasis are unaffected. Novelty: The main finding of this study is that localized heating increased TFAM mRNA expression. The normal exercise-induced increased PGC-1α gene expression was unaltered by local muscle heating.

The Acute Effects of Exercise and Temperature on Regional mtDNA.

A reduced mitochondrial DNA (mtDNA) copy number, the ratio of mitochondrial DNA to genomic DNA (mtDNA:gDNA), has been linked with dysfunctional mitochondria. Exercise can acutely induce mtDNA damage manifested as a reduced copy number. However, the influence of a paired (exercise and temperature) intervention on regional mtDNA (MINor Arc and MAJor Arc) are unknown. Thus, the purpose of this study was to determine the acute effects of exercise in cold (7 °C), room temperature (20 °C), and hot (33 °C) ambient temperatures, on regional mitochondrial copy number (MINcn and MAJcn). Thirty-four participants (24.4 ± 5.1 yrs, 87.1 ± 22.1 kg, 22.3 ± 8.5 %BF, and 3.20 ± 0.59 L·min-1 VO2peak) cycled for 1 h (261.1 ± 22.1 W) in either 7 °C, 20 °C, or 33 °C ambient conditions. Muscle biopsy samples were collected from the vastus lateralis to determine mtDNA regional copy numbers via RT-qPCR. mtDNA is sensitive to the stressors of exercise post-exercise (MIN fold change, -1.50 ± 0.11; MAJ fold change, -1.70 ± 0.12) and 4-h post-exercise (MIN fold change, -0.82 ± 0.13; MAJ fold change, -1.54 ± 0.11). The MAJ Arc seems to be more sensitive to heat, showing a temperature-trend (p = 0.056) for a reduced regional copy number ratio after exercise in the heat (fold change -2.81 ± 0.11; p = 0.019). These results expand upon our current knowledge of the influence of temperature and exercise on the acute remodeling of regional mtDNA.

Acute effects of functional dry needling on skeletal muscle function.

INTRODUCTION: Functional dry needling (FDN) is commonly used to treat soft tissue pain-related conditions. Previous research has demonstrated benefits to chronic resistance training; however, objective physiological measures sensitive to acute exercise have not been found. The purpose of this study was to evaluate the acute effects of FDN on muscle strength and endurance. METHODS: Ten subjects (height 168 ± 9 cm, mass 68.2 ± 11.3 kg) were tested bilaterally (pre and post) for vastus lateralis (VL) isometric strength, isokinetic fatigue index, muscle electrical activity, and muscle oxygenation. FDN was administered to one leg, while the other served as a control. RESULTS: Limited acute effects of functional dry needling were observed (p < 0.05). DISCUSSION: FDN does not appear to acutely improve muscle function in healthy young adults. Although there were no improvements in muscle function, there were no adverse effects either, contributing to the safety of FDN healthy populations. CONCLUSION: Acute FDN does not appear to enhance muscle performance in a healthy, non-clinical population. Thus, clinicians should consider the population and desired outcome when applying FDN.

Effect of local cold application during exercise on gene expression related to mitochondrial homeostasis.

Exercise training increases mitochondrial content in active skeletal muscle. Previous work suggests that mitochondrial-related genes respond favorably to exercise in cold environments. However, the impact of localized tissue cooling is unknown. The purpose of this study was to determine the impact of local muscle cooling during endurance exercise on human skeletal muscle mitochondrial-related gene expression. Twelve subjects (age, 28 ± 6 years) cycled at 65% peak power output. One leg was cooled (C) for 30 min before and during exercise with a thermal wrap while the other leg was wrapped but not cooled, room temperature (RT). Muscle biopsies were taken from each vastus lateralis before and 4 h after exercise for the analysis of gene expression. Muscle temperature was lower in the C (29.2 ± 0.7 °C) than the RT (34.1 ± 0.3 °C) condition after pre-cooling for 30 min before exercise (p < 0.001) and remained lower after exercise in the C (36.9 ± 0.5) than the RT (38.4 ± 0.2, p < 0.001) condition. PGC-1α and NRF1 mRNA expression were lower in the C (p = 0.012 and p = 0.045, respectively) than the RT condition at 4 h after exercise. There were no temperature-related differences in other genes (p > 0.05). These data suggest that local cooling has an inhibitory effect on exercise-induced PGC-1α and NRF1 expression in human skeletal muscle. Those considering using local cooling during exercise should consider other systemic cooling options. Novelty: Local cooling has an inhibitory effect on exercise-induced PGC-1α and NRF1 expression in human skeletal muscle. Local cooling may lead to a less robust exercise stimulus compared with standard conditions.

Exercise- and Cold-Induced Human PGC-1α mRNA Isoform Specific Responses.

Cold exposure in conjunction with aerobic exercise stimulates gene expression of PGC-1α, the master regulator of mitochondrial biogenesis. PGC-1α can be expressed as multiple isoforms due to alternative splicing mechanisms. Among these isoforms is NT-PGC-1α, which produces a truncated form of the PGC-1α protein, as well as isoforms derived from the first exon of the transcript, PGC-1α-a, PGC-1α-b, and PGC-1α-c. Relatively little is known about the individual responses of these isoforms to exercise and environmental temperature. Therefore, we determined the expression of PGC-1α isoforms following an acute bout of cycling in cold (C) and room temperature (RT) conditions. Nine male participants cycled for 1h at 65% Wmax at -2 °C and 20 °C. A muscle biopsy was taken from the vastus lateralis before and 3h post-exercise. RT-qPCR was used to analyze gene expression of PGC-1α isoforms. Gene expression of all PGC-1α isoforms increased due to the exercise intervention (p < 0.05). Exercise and cold exposure induced a greater increase in gene expression for total PGC-1α (p = 0.028) and its truncated isoform, NT-PGC-1α (p = 0.034), but there was no temperature-dependent response in the other PGC-1α isoforms measured. It appears that NT-PGC-1α may have a significant contribution to the reported alterations in the exercise- and temperature-induced PGC-1α response.

Randomized controlled pilot study of customized pamphlets to promote physical activity and symptom self-management in women with multiple sclerosis.

OBJECTIVE: Investigate the feasibility and potential efficacy of a customized print-based intervention to promote physical activity and symptom self-management in women with multiple sclerosis. DESIGN: A randomly allocated two-group repeated measures design, with a delayed-treatment contact group serving as the control. Participants were randomized to receive the intervention immediately (n =14) or receive it at week 12 (n =16). Outcome measures were administered at weeks 1, 12, and 24. SETTING: Community-based in metropolitan area. SUBJECTS: Thirty women with multiple sclerosis. INTERVENTION: Prescribing a home-exercise program and following up with customized pamphlets, which are matched to participants' stage of readiness to change physical activity behavior and physical activity barriers (e.g. encouraging self-management of symptoms). MAIN MEASURES: Physical Activity and Disability Survey-revised, Godin Leisure-Time Exercise Questionnaire, SF-12, Symptoms of Multiple Sclerosis Scale, and 6-minute walk test. RESULTS: Intent-to-treat analyses using mixed multivariate analysis of variance (MANOVA) were conducted on (1) physical activity levels and (2) health and function outcomes. The mixed MANOVAs for physical activity levels and health and function outcomes indicated significant improvements in the immediate group compared with the delayed group (i.e. condition by time interaction was significant, Wilks' λ = 0.59, F(2, 27) = 9.31, P = 0.001 and Wilks' λ = 0.70, F(4, 25) = 2.72, P = 0.052, respectively). The intervention had moderate to large effect sizes in improving physical activity levels (d = 0.63 to 0.89), perceptions of physical function (d = 0.63), and 6-minute walk test (d=0.86). CONCLUSION: This pilot study indicates that a customized print-based intervention shows promise in improving physical activity levels and health and function in women with multiple sclerosis.

A Model of Community-Based Behavioral Intervention for Depression in Diabetes: Program ACTIVE.

Depression affects one in four people with diabetes and significantly affects diabetes health. Earlier studies of the treatment of depression have documented that cognitive behavioral therapy (CBT) and exercise have each been found to be effective in treating depression in people with and without diabetes in the context of medical settings. Individuals in rural areas lack regular access to medical centers and require treatment options that may be adapted for local communities. To date, no studies have combined CBT and exercise for people with diabetes. This article presents a translational behavioral depression intervention study designed for individuals with type 2 diabetes in a rural Appalachian region as a model of an interdisciplinary approach to the treatment of depression in diabetes.