Efficacy of Chemically Distinct Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and Pain Phenotypes in Adhesive Capsulitis

Overview

Patients aged 18-75 years who present to a tertiary rehabilitation hospital with shoulder pain and restricted range of motion, and who consent to participate, will be included in the study. Eligibility will be determined based on predefined inclusion and exclusion criteria. Eligible patients will be randomly assigned to receive one of several nonsteroidal anti-inflammatory drugs (NSAIDs) with differing chemical properties (e.g., diclofenac, meloxicam, or indomethacin), in combination with a home-based exercise program for shoulder adhesive capsulitis. Patients' sociodemographic data, as well as detailed clinical and examination findings and baseline outcomes, will be recorded. Patients will be informed about their condition, and modifications to activities of daily living will be recommended.Patients' pain phenotypes (nociceptive, neuropathic, nociplastic) will be categorized based on clinical history and questionnaires, and it will be determined which pain types derive greater benefit from NSAIDs. Follow-up assessments will be conducted at the end of the first and second weeks. At the first-week follow-up, pain intensity will be evaluated using the Visual Analog Scale (VAS). If the treatment is deemed effective (defined as a ≥3-point reduction or ≥50% decrease in VAS), the same NSAID will be continued for an additional week; otherwise, it will be switched to an alternative NSAID with a different biochemical profile (group). The outcomes assessments will be performed by a blinded evaluator to minimize bias.

This study will include patients presenting to the Physical Medicine and Rehabilitation outpatient clinics of Konya Beyhekim Training and Research Hospital with shoulder pain and restricted range of motion, who are clinically diagnosed with frozen shoulder following a comprehensive evaluation. All patients will be prescribed non-steroidal anti-inflammatory drugs (NSAIDs) as part of analgesic treatment. A total of 120 consecutive patients aged 18-75 years, with shoulder pain lasting at least one month and diagnosed with frozen shoulder after appropriate differential diagnosis, who consent to participate, will be enrolled. All participants will provide written informed consent for study participation. Sociodemographic characteristics and clinical examination findings will be recorded for all participants. As part of the clinical examination, patients will be evaluated for diagnosis and differential diagnosis based on the presence of impingement tests, drop arm sign, shoulder ultrasonography (presence of significant effusion, rotator cuff tear), and plain radiography. Following assessment according to predefined inclusion and exclusion criteria, patients will be randomized (block randomization) to receive one of several NSAIDs with distinct chemical properties (e.g., diclofenac, meloxicam, or indomethacin). Patients' sociodemographic data, as well as detailed clinical and examination findings and baseline outcomes, will be recorded. Patients will be informed about their condition, and modifications to activities of daily living will be recommended. Patients' pain phenotypes (nociceptive, neuropathic, nociplastic) will be categorized based on clinical history and questionnaires, and it will be determined which pain types derive greater benefit from NSAIDs. As a home exercise program, patients will perform range-of-motion exercises, Codman exercises, isometric strengthening, and stretching within their self-limited pain threshold. Exercise adherence will be monitored at the first and second visits, and patients with less than 70% adherence will be excluded. Patients will be re-evaluated one week after treatment initiation. Pain will be assessed based on perceived pain relief, Visual Analog Scale (VAS; 0-10), and overall treatment effectiveness. Patients demonstrating a clinically meaningful response-defined as at least a 50% reduction in pain or a decrease of ≥3 points on the VAS-will continue the same NSAID for an additional week, provided no adverse effects or contraindications arise. These patients will undergo a final evaluation at the end of the second week. For patients who do not show sufficient improvement at the first-week assessment, the prescribed NSAID will be randomly switched to an alternative NSAID agent with different chemical properties (including both switching within the same chemical class-for example, from diclofenac to etodolac-and switching to a different chemical class with distinct properties-for example, from diclofenac to meloxicam). These patients will continue treatment for an additional week and will be reassessed at the end of the second week, at which point treatment effectiveness will be recorded. After two weeks, the medical treatment and exercise program will be completed, and the outcomes at the end of week 2 will be assessed by a blinded evaluator, marking the completion of the study. In addition, any NSAID-related side effects (dyspepsia, nausea, headache, hypertension, gastrointestinal hemorrhage, etc.) will be recorded, and patient satisfaction (subjective impression of improvement) level will be assessed by a blind investigator using a Likert-type questionnaire (1; not satisfied at all, 5; very satisfied). The study will be concluded once a total of 120 consecutive patients meeting the inclusion criteria have been enrolled.