Schwann cell insulin-like growth factor receptor type-1 mediates metastatic bone cancer pain in mice.

Insulin growth factor-1 (IGF-1), an osteoclast-dependent osteolysis biomarker, contributes to metastatic bone cancer pain (MBCP), but the underlying mechanism is poorly understood. In mice, the femur metastasis caused by intramammary inoculation of breast cancer cells resulted in IGF-1 increase in femur and sciatic nerve, and IGF-1-dependent stimulus/non-stimulus-evoked pain-like behaviors. Adeno-associated virus-based shRNA selective silencing of IGF-1 receptor (IGF-1R) in Schwann cells, but not in dorsal root ganglion (DRG) neurons, attenuated pain-like behaviors. Intraplantar IGF-1 evoked acute nociception and mechanical/cold allodynia, which were reduced by selective IGF-1R silencing in DRG neurons and Schwann cells, respectively. Schwann cell IGF-1R signaling promoted an endothelial nitric oxide synthase-mediated transient receptor potential ankyrin 1 (TRPA1) activation and release of reactive oxygen species that, via macrophage-colony stimulating factor-dependent endoneurial macrophage expansion, sustained pain-like behaviors. Osteoclast derived IGF-1 initiates a Schwann cell-dependent neuroinflammatory response that sustains a proalgesic pathway that provides new options for MBCP treatment.

miRNA-203b-3p Induces Acute and Chronic Pruritus through 5-HTR2B and TRPV4.

Growing evidence indicates that transient receptor potential (TRP) channels contribute to different forms of pruritus. However, the endogenous mediators that cause itch through transient receptor potential channels signaling are poorly understood. In this study, we show that genetic deletion or pharmacological antagonism of TRPV4 attenuated itch in a mouse model of psoriasis induced by topical application of imiquimod. Human psoriatic lesions showed increased expression of several microRNAs, including the miR-203b-3p, which induced a calcium ion response in rodent dorsal root ganglion neurons and scratching behavior in mice through 5-HTR2B activation and the protein kinase C‒dependent phosphorylation of TRPV4. Computer simulation revealed that the miR-203b-3p core sequence (GUUAAGAA) that causes 5-HTR2B/TRPV4-dependent itch targets the extracellular side of 5-HTR2B by interacting with a portion of the receptor pocket consistent with its activation. Overall, we reveal the unconventional pathophysiological role of an extracellular microRNA that can behave as an itch promoter through 5-HTR2B and TRPV4.

Monitoring Training Load in Soccer: The ROMEI Model.

ABSTRACT: Montini, M and Rocchi, JE. Monitoring training load in soccer: The Relation of Ongoing Monitored Exercise in Individual model. J Strength Cond Res 36(9): 2566-2572, 2022. For a training organization, monitoring training load (TL) is of paramount importance. Despite this, a conclusive response on such topic is yet to be reported. The aims of this study were to investigate the relationship between TL indicators and to propose a new method for monitoring TL response and physical fitness. Twenty professional soccer players were retrospectively evaluated. The first phase of data analysis included 34 in-season training sessions. Subsequently, three microcycles (T1-T2-T3) of pre-season training were processed. A regression model was used to examine the relationships between internal TL (session rating of perceived exertion [s-RPE]) and external TL (energy expenditure, EE). The standard error of the regression equation was used to propose a new model called "ROMEI" (Relation of Ongoing Monitored Exercise in Individual). The level of statistical significance was set at p < 0.05. During the competitive season and the pre-season training camp, the average TL values were 65.8 ± 22 and 58.2 ± 22 minutes; 336 ± 204 and 228 ± 101 AU of s-RPE; and 29 ± 13 and 25 ± 9 kJ kJ -1 of EE, respectively. In the competitive season, the collective and average individual correlation coefficients between s-RPE and EE were r = 0.888 and r = 0.892 ± 0.05, respectively. Considering slope values ( m ) of the regression line, data highlighted a significant increase of +34.4 ± 15.9% in T2 vs. T3 ( p < 0.001) and +38.2 ± 15.2% in T1 vs. T3 ( p < 0.001). Data shown in this investigation support the use of an individualized analysis to better understand the TL administered to soccer players rather than a collective analysis. This may be accomplished with the proposed ROMEI model.

Respiratory Frequency as a Marker of Physical Effort During High-Intensity Interval Training in Soccer Players.

PURPOSE: Variables currently used in soccer training monitoring fail to represent the physiological demand of the player during movements like accelerations, decelerations, and directional changes performed at high intensity. We tested the hypothesis that respiratory frequency (fR) is a marker of physical effort during soccer-related high-intensity exercise. METHODS: A total of 12 male soccer players performed a preliminary intermittent incremental test and 2 shuttle-run high-intensity interval training (HIIT) protocols, in separate visits. The 2 HIIT protocols consisted of 12 repetitions over 9 minutes and differed in the work-to-recovery ratio (15:30 vs 30:15 s). Work rate was self-paced by participants to achieve the longest possible total distance in each HIIT protocol. RESULTS: Work-phase average metabolic power was higher (P < .001) in the 15:30-second protocol (31.7 [3.0] W·kg-1) compared with the 30:15-second protocol (22.8 [2.0] W·kg-1). Unlike heart rate and oxygen uptake, fR showed a fast response to the work-recovery alternation during both HIIT protocols, resembling changes in metabolic power even at supramaximal intensities. Large correlations (P < .001) were observed between fR and rating of perceived exertion during both 15:30-second (r = .87) and 30:15-second protocols (r = .85). CONCLUSIONS: Our findings suggest that fR is a good marker of physical effort during shuttle-run HIIT in soccer players. These findings have implications for monitoring training in soccer and other team sports.

Neuromuscular demand in a soccer match assessed by a continuous electromyographic recording.

BACKGROUND: The bulk of research investigating soccer player's performance has been concentrated on the metabolic demand, while only few studies focused on the neuromuscular activation. The present study aimed at investigating the activation profile of the leg muscles throughout a 90- minute soccer match. METHODS: Fifteen football players (18.3±0.7 years) performed: 1) an isometric maximal voluntary contraction (MVC) before the game [MVCpre]; 2) a 90-minute soccer match (composed of two 45-minute periods separated by a 15-minute rest); 3) a second MVC after the match [MVCpost]. Electromyographic (EMG) activity of the Vastus Lateralis (VL) muscle of the dominant leg was recorded during the match. The root mean square (RMS) of the EMG signals was normalized for the maximal RMS obtained during the MVCpre (100%RMSmax) and six intensity classes were created in order to represent the %RMS distribution during the match (1st: 0-20%RMSmax; 2nd: 20-40%RMSmax; 3rd: 40-60%RMSmax; 4th: 60-80%RMSmax; 5th: 80-100%RMSmax; 6th: 100-120%RMSmax). RESULTS: After the 90-minute soccer match, knee extensor MVC failed to show any statistical difference from pre-game values (-4.2%; P>0.05) whilst the neuromuscular activation demonstrated a significant reduction (-26.3%, P<0.01). During the game, the mean total distribution of RMS of the players was: 84.8±7.1% of total time in the 1st class, 8.5±3.9% in the 2nd, 3.6±1.6% in the 3rd, 1.7±1.0% in the 4th, 0.9±0.6% in the 5th and 0.4±0.5% in the 6th class of intensity. There was a significant difference (P<0.05) between the first versus the second half for the classes 1st, 3rd and 4th. CONCLUSIONS: This represents the first attempt to characterize the neuromuscular activation profile during a 90-minute soccer match. Integrating this approach with more traditional ones may help further our understanding of the physiological demand of competitive soccer.

Caffeine improves neuromuscular function during maximal dynamic exercise.

INTRODUCTION: In this study we tested the hypothesis that caffeine supplementation improves neuromuscular function, which has both nutritional and clinical relevance. METHODS: Fourteen male subjects (mean ± SD: 23.8 ± 2.8 years) volunteered in a double-blind, repeated-measures study with placebo (PLA) or caffeine (CAFF) (6 mg kg(-1)). Maximal voluntary isometric contractions (MVCs), evoked maximal twitch, and maximal isokinetic contractions during elbow flexion were assessed. Mechanical and electromyographic (EMG) signals from the biceps brachii muscle were recorded, and muscle fiber conduction velocity (CV) was calculated to evaluate changes in the muscle force-velocity relationship and muscle fiber recruitment. RESULTS: The torque-angular velocity curve was enhanced after CAFF supplementation. This was supported by a concomitant increase of CV values (8.7% higher in CAFF). CONCLUSIONS: Caffeine improves muscle performance during short-duration maximal dynamic contractions. The concomitant improvement of mean fiber CV supports the hypothesis of an effect of caffeine on motor unit recruitment.