P2X3 and P2X2/3 receptors are promising therapeutic targets for pain treatment and selective inhibitors are under evaluation in ongoing clinical trials. Here we aim to consolidate and quantitatively evaluate the preclinical evidence on P2X3 and P2X2/3 receptors inhibitors for pain treatment. A literature search was conducted in PubMed, Scopus and Web-of-Science on August 5, 2023. Data was extracted and meta-analyzed using a random-effects model to estimate the analgesic efficacy of the intervention; then several subgroup analyses were performed. 67 articles were included. The intervention induced a consistent pain reduction (66.5 [CI95% = 58.5, 74.5]; p < 0.0001), which was highest for visceral pain (114.3), followed by muscle (79.8) and neuropathic pain (71.1), but lower for cancer (64.1), joint (57.5) and inflammatory pain (49.0). Further analysis showed a greater effect for mechanical hypersensitivity (70.4) compared to heat hypersensitivity (64.5) and pain-related behavior (54.1). Sex (male or female) or interspecies (mice or rats) differences were not appreciated (p > 0.05). The most used molecule was A-317491, but other such as gefapixant or eliapixant were also effective (p < 0.0001 for all). The analgesic effect was higher for systemic or peripheral administration than for intrathecal administration. Conversely, intracerebroventricular administration was not analgesic, but potentiated pain. P2X3 and P2X2/3 receptor inhibitors showed a good analgesic efficacy in preclinical studies, which was dependent on the pain etiology, pain outcome measured, the drug used and its route of administration. Further research is needed to assess the clinical utility of these preclinical findings. PROSPERO ID CRD42023450685.

Objectives: This study aimed to explore the effects of four days of Rhodiola Rosea (RR) supplementation on bench-press and bench-pull exercises under resting or mental fatigue conditions in young healthy individuals. Methods: Eighteen participants (seven women) visited the laboratory on five occasions separated by 7 days—one preliminary session and four experimental sessions. In the preliminary session, participants were familiarised with the Stroop and Multiple Object Tracking tests, after which their one-repetition maximum loads for bench presses and bench pulls were determined. The four experimental sessions had the same protocol, differing only in the supplement (RR or placebo) and mental task conditions (Stroop test or control video). Participants were assigned randomly and counterbalanced to each experimental condition: (I) RR and Stroop test, (II) RR and control video, (III) placebo and Stroop test, and (IV) placebo and control video. Results: The main findings indicate that RR supplementation has trivial-to-small effects in terms of mental fatigue, visuo-cognitive processing, or perceived exertion. However, RR was significantly superior to placebo on strength performance in the control video condition during some sets, as it increased the number of repetitions performed in the bench press and the fastest velocity in the bench pull. Out of 52 comparisons, 17 small effect sizes were observed, with 14 favouring RR and 3 favouring placebo, with the remaining differences being trivial. Conclusions: These results suggest that short-term RR supplementation is safe and provides its main ergogenic effects on physical performance rather than in visuo-cognitive or mental outcomes.

Purpose: Although previous studies have compared strength-training adaptations between free weights (FW) and machine-guided exercises, those studies did not use a Smith machine (SM), which most closely replicates the exercises performed with FW. Thus, the aim of the present study was to investigate the chronic effects of strength-focused, velocity-based training regimens using FW versus SM. Methods: Thirty-seven sport-science students (14 female) were assigned, balanced by sex and relative strength, to either an FW or SM training group. The training program lasted 8 weeks (2 sessions/wk), and participants performed 4 sets per exercise (back squat and bench press) at 70% of their 1-repetition maximum with moderate effort levels (20%–25% velocity loss). Load–velocity profile parameters (load-axis intercept, velocity-axis intercept, and area under the load–velocity relationship line), cross-sectional areas of the vastus lateralis and pectoralis major muscles, and the number of repetitions to failure in the bench-press exercise were assessed before and after the training program. Mechanical variables were assessed using both FW and SM. Results: All variables, with the exception of back-squat velocity-axis intercept (P = .124), improved in both training groups. The changes in load-axis intercept and area under the load–velocity relationship line were more pronounced when the training and testing conditions matched. Failure in the bench-press exercise and cross-sectional areas of the vastus lateralis and pectoralis major showed comparable improvements for both training groups, while velocity-axis intercept tended to improve more in the SM group. Conclusions: The general population, unconcerned with the specificity of strength adaptations, can choose a training modality (FW or SM) based on personal preferences.

The present systematic review aimed to determine the chronic effects of the combination of transcranial direct current stimulation (tDCS) and exercise on motor function and performance outcomes. We performed a systematic literature review in the databases MEDLINE and Web of Science. Only randomized control trials that measured the chronic effect of combining exercise (comprising gross motor tasks) with tDCS during at least five sessions and measured any type of motor function or performance outcome were included. A total of 22 interventions met the inclusion criteria. Only outcomes related to motor function or performance were collected. Studies were divided into three groups: (a) healthy population (n = 4), (b) neurological disorder population (n = 14), and (c) musculoskeletal disorder population (n = 4). The studies exhibited considerable variability in terms of tDCS protocols, exercise programs, and outcome measures. Chronic use of tDCS in combination with strength training does not enhance motor function in healthy adults. In neurological disorders, the results suggest no additive effect if the exercise program includes the movements pretending to be improved (i.e., tested). However, although evidence is scarce, tDCS may enhance exercise-induced adaptations in musculoskeletal conditions characterized by pain as a limiting factor of motor function.

The objective of this study was to compare a number of variables derived from the vertical and horizontal force components between loaded countermovement jumps performed in a Smith machine (SM modality; vertically restrained jumps) and with free weights (FW modality; unrestrained jumps). Twenty-three recreationally trained individuals, 6 women and 17 men, performed on a 3D force platform 5 maximal countermovement jump trials against 3 external loads (30%, 50%, and 70% of the SM 1-repetition maximum) using the SM and FW jumping modalities on separate sessions. The SM modality promoted greater values for virtually all the variables derived from the vertical force component (maximal force, maximal and minimum velocity, and impulse) and also shorter durations of the braking and propulsive phases. Regardless of the countermovement jump phase (braking or propulsive), the impulse directed toward the backward direction was always considerably greater for the SM compared with the FW modality. These results evidence that for recreationally trained individuals, the SM modality could be more effective to increase the general force capacity of the leg muscles due to increased external stability, while the FW modality is preferable when the orientation of force application is a crucial consideration, as it reduces the horizontal force component.

The purpose of this study was to compare the reaction forces, power and the kinematics of the center of mass (CM) during the performance of jump squats using the Smith machine (SM) and the free weight (FW). In this study participated twenty-four athletes with experience in jumping activities and training with loads. In addition to a Smith machine, a Dinascan / IBV force platform has been used at 500 Hz. After obtaining the maximum load for each participant (1RM), the components of the reaction force (FR (X) and FR (Y)) were recorded in three load levels, with respect to their corresponding 1RM (30 %, 50% and 70%). The kinematics of the CM was obtained from the integration of the acceleration with respect to time after dividing the net force (FN) by the mass of the system (m). From the analysis of the performance times and the reaction forces, it is suggested that the FW situation would be more suitable to look for a real approach to the competition, being a movement that produces a greater postural control. The SM situation reduces the execution time and increases the momentum developed during the propulsive phase, which suggests that it could be more suitable for training the development of force at high speeds of concentric contraction.