This thesis conducts a thorough examination of the synergistic impact of neuromuscular electrical stimulation (NMES) combined with blood flow restriction (BFR) on muscular adaptations and pain modulation in healthy and knee osteoarthritis (OA) populations. The primary objective across subsequent chapters is to establish the superior efficacy of NMES+BFR over NMES alone, aiming to optimise muscular adaptations and modulate pain, potentially contributing to improved clinical outcomes and enhancing muscular adaptations without exercise. Chapter 2 commences with a scoping literature review, identifying gaps and inconsistencies in existing research on NMES+BFR and drawing upon the wider literature bases of both to develop an evidence based methodology. Notably, methodological disparities in BFR and NMES application, namely not using arterial occlusion pressure (AOP) to prescribe the BFR stimulus and not using NMES frequencies and intensities found to enhance muscular strength, with these emerging as key contributors to the varying evidence base regarding their combined effectiveness in enhancing muscle strength and size outcomes. Chapter 3 provides a comprehensive overview of the research methods employed, establishing a consistent framework for subsequent studies. Chapter 4 optimises NMES+BFR methodologies, by using NMES recommended parameters and combining it with BFR using AOP (40-80%) to standardise the restrictive pressure. This study assessed acute measures of fatigue (surrogate marker for chronic training adaptations), muscle swelling, RPE, pain perception, and cardiovascular safety. Findings revealed increased fatigue after NMES+BFR (80%) compared to NMES alone. However, acute fatigue was observed after all NMES+BFR conditions, but greater perceptual pain and RPE reported after 60% vs. 40% AOP, therefore, eliminating the NMES combined with 60% condition from future investigation. Importantly, this chapter refines intervention parameters for a subsequent training study. Chapter 5 focuses on a chronic training study to assess the effectiveness of NMES+BFR (40% and 80%) in increasing muscle strength and size compared to NMES alone. A 6-week, 3-sessions-per-week randomised controlled trial was undertaken. Findings showed greater improvements in muscle strength (isometric and eccentric) and muscle size were observed in NMES+BFR groups, accompanied by greater NMES stimulation intensities tolerated during the training sessions compared to NMES alone. Due to the greater NMES stimulation intensity tolerated in Chapter 5 and the wider BFR evidence base reporting acute reductions in pressure pain and thermal pain thresholds, Chapter 6 investigated the acute effects of pressure, thermal and temporal summation of pain (TSP) thresholds in healthy adults, revealing an acute increase in pressure pain thresholds immediately after NMES+BFR, explaining the greater tolerated currents observed in Chapter 5. Chapter 7 replicates the methodology in a clinical population (knee osteoarthritis patients), due to this population demonstrating altered exercise induced hypoalgesia responses to healthy adults, which has been proposed as a main mechanism for reduced pain after BFR exercise. The results demonstrated acute increases in pressure pain thresholds, improvements in sit-to-stand performance, and reduced TSP after NMES+BFR (80%), with no effects observed after NMES alone. Cardiovascular safety is confirmed. Chapter 8 synthesises and discusses the findings, emphasising the potential of NMES+BFR in enhancing strength and hypertrophy and modulating pain in healthy and knee OA patients without requiring exercise. In summary, this thesis offers a comprehensive exploration of NMES+BFR, showcasing its potential to enhance muscular adaptations and pain modulation in both healthy and clinical populations. The research underscores the promise of this intervention in improving clinical outcomes and providing a pre exercise intervention when exercise is not possible due to pain or contraindicated to enhance muscular adaptations and modulate pain.
