Shoulder pain is one of the primary reasons for seeking physiotherapy care. The high prevalence of rotator cuff-related shoulder pain underscores the need for research into novel treatment approaches that may enhance the clinical outcomes of conventional physiotherapy interventions. Immersive Virtual Reality (IVR) has been demonstrated to serve as an effective adjunct for pain management by providing distraction and altering patients' pain perception. Specifically, when used alongside exercise, IVR has been shown to induce hypoalgesia in individuals with chronic low back pain. Additionally, IVR is emerging as a promising tool to enhance motivation and improve adherence to rehabilitation protocols, which is critical for long-term treatment implementation and achieving positive outcomes. These findings suggest that virtual reality may provide an innovative approach to managing pain in patients with rotator cuff-related shoulder pain, improving their pain experience, functionality, and quality of life. To date, no study has directly compared the effectiveness of combining IVR with standard physiotherapy treatments versus standard treatments alone on clinical variables, clinimetric measures, and biomarkers in individuals with persistent shoulder pain related to the rotator cuff. Therefore, conducting a randomized multicenter clinical trial on this subject, facilitated by international collaboration among RIU-affiliated universities, could provide a robust foundation for implementing new technologies such as virtual reality in pain management and advancing rehabilitation strategies. The objective of this project is as follows: To compare the effectiveness of combining immersive virtual reality with standard physiotherapy treatment versus standard treatment alone on clinical variables, clinimetric measures, and biomarkers in individuals with persistent rotator cuff-related shoulder pain.

Shoulder pain represents the third most common cause of musculoskeletal pain and the leading cause of non-traumatic upper limb pain. This condition holds significant musculoskeletal relevance, as up to 66.7% of individuals experience shoulder pain at least once in their lifetime, and symptoms persist beyond 18 months in 50% of cases, impacting daily activities at home and in the workplace. Furthermore, shoulder pain can disrupt sleep patterns and contribute to work-related challenges, such as sick leave, early retirement, or job loss. Persistent shoulder pain also imposes significant socioeconomic costs, estimated at $7 billion in the United States in 2000 and exceeding €1.5 million between 2004 and 2007 in the Canary Islands, Spain. Physiotherapy has emerged as a promising approach for managing this condition. In Sweden, patients receiving physiotherapy as a first-line treatment generated lower total healthcare costs. Similarly, in the United States, musculoskeletal patients who initiated care with physiotherapy achieved better cost-effectiveness, required fewer sessions, and experienced greater functional recovery. Diagnosing shoulder pain accurately remains challenging for clinicians, primarily due to inconsistencies and a lack of uniformity in diagnostic nomenclature and criteria. Consequently, diagnosis may need to rely on sub-classifications of patients with reliably reproducible characteristics. In this context, rotator cuff-related shoulder pain is consistently reported as the most prevalent diagnosis in individuals with shoulder pain. Patients with rotator cuff-related shoulder pain often report moderate-to-severe pain intensity, limitations in daily activities, reduced range of motion, and/or loss of strength. Persistent pain in this condition is also commonly associated with psychosocial factors, such as fear of movement, pain hypervigilance, and/or loss of self-efficacy-barriers that can hinder recovery. Collectively, these factors significantly affect patients' quality of life. A novel aspect of this project is the proposed examination of biomarkers associated with systemic inflammation and chronic pain in this clinical population, specifically C-reactive protein (CRP) and calcitonin gene-related peptide (CGRP). C-reactive protein is a marker of systemic inflammation, with elevated levels linked to various chronic pain conditions, suggesting an inflammatory component that may modulate pain perception and intensity in these patients. Meanwhile, CGRP is a neuropeptide involved in nociceptive signal transmission and inflammatory response modulation. Elevated CGRP levels have been documented in several chronic pain conditions, including osteoarthritis, migraines, and joint disorders, where peripheral and central sensitization processes are present. In animal studies, CGRP has been shown to play a role in triggering neurogenic inflammation and its association with pain pathways. In conditions like rotator cuff-related shoulder pain, characterized by persistent pain, complex interactions between inflammatory processes and neurobiological mechanisms are likely to occur. Evaluating these biomarkers is particularly relevant to deepen our understanding of the underlying pathophysiological mechanisms in this patient population. The use of virtual reality (VR) has emerged as an innovative strategy for managing patients with pain, disability, and reduced quality of life. On one hand, it can modulate the context of motor relearning, an aspect of particular relevance for individuals with persistent shoulder pain, where strength and mobility deficits are common. On the other hand, the hypoalgesic mechanisms underlying the effects of VR are multifactorial, mediated by various dimensions of the pain experience, including sensory-discriminative, affective-motivational, and evaluative-cognitive aspects, as well as motor behavior itself. Moreover, VR appears to modulate pain perception by stimulating auditory, visual, and sensorimotor neural networks and activating descending inhibitory systems, thereby influencing pain perception. Interestingly, severe pain and disability, rather than being contraindications, may serve as indications for implementing VR. This therapeutic approach can also be tailored to the individual needs of patients, considering factors such as functional levels, social context, and age, which may influence adaptability to the technology and, consequently, treatment adherence and outcomes. Finally, VR has demonstrated its potential as a high-quality, cost-effective treatment option for chronic low back pain, highlighting its capacity to provide an accessible and effective alternative that reduces the economic burden on healthcare systems and patients alike.