Peripheral Anesthetic Interventions in Fibromyalgia: A systematic review with exploratory quantitative synthesis of Lidocaine-Based Therapies, Neural Therapy, and Peripheral Nerve Blocks

Background Fibromyalgia (FM) is a chronic nociplastic pain disorder characterized by widespread pain, fatigue, sleep disturbances, cognitive dysfunction, and impaired quality of life. Although FM has traditionally been conceptualized as a central sensitization syndrome, increasing evidence suggests that peripheral nociceptive input, small fiber pathology, and neuroimmune dysregulation may contribute to symptom generation and maintenance. Peripheral anesthetic interventions, including intravenous lidocaine, local anesthetic infiltrations, neural therapy, and peripheral nerve blocks, have emerged as potential therapeutic strategies targeting these mechanisms. Objective To systematically review the available evidence regarding the efficacy and safety of peripheral anesthetic interventions in patients with fibromyalgia and to explore their mechanistic implications within the nociplastic pain framework. Methods A systematic search was conducted in PubMed/MEDLINE, Embase, Scopus, Web of Science, Cochrane CENTRAL, CINAHL, SciELO, and LILACS from inception to January 2026. Eligible studies included randomized controlled trials, prospective studies, and observational interventional studies evaluating peripheral anesthetic interventions in adult FM patients diagnosed according to American College of Rheumatology criteria. Primary outcomes included pain reduction assessed by Visual Analog Scale (VAS) or equivalent validated measures. Secondary outcomes included Fibromyalgia Impact Questionnaire (FIQ/FIQR), quality of life, fatigue, depression, and adverse events. Risk of bias was assessed using ROB2 and ROBINS-I tools. Due to substantial methodological heterogeneity among included studies, an exploratory quantitative synthesis was performed when appropriate. Results A total of 635 records were identified, of which 18 studies were included in the qualitative synthesis and 12 studies provided sufficient data for exploratory quantitative synthesis. Interventions included intravenous lidocaine infusions, neural therapy, local anesthetic injections, and peripheral nerve blocks. Overall, peripheral anesthetic interventions were associated with clinically meaningful short-term reductions in pain severity and improvements in functional outcomes. Intravenous lidocaine demonstrated the most consistent short-term analgesic effects across studies, whereas neural therapy combined with exercise showed broader improvements in pain and quality-of-life measures compared with exercise alone. Mechanistic evidence from included studies supported the contribution of peripheral sensitization and small fiber dysfunction to FM pathophysiology. However, substantial clinical heterogeneity, methodological limitations, and limited long-term follow-up were observed across studies. The overall certainty of evidence ranged from low to very low. Conclusion Peripheral anesthetic interventions appear to provide clinically relevant analgesic benefits in selected patients with fibromyalgia and support the concept that peripheral nociceptive mechanisms contribute to FM pathophysiology. These findings reinforce a multidimensional model of fibromyalgia involving dynamic interactions between peripheral and central sensitization mechanisms. Larger, rigorously designed randomized controlled trials with mechanistic biomarker integration are needed to better define responder phenotypes and optimize therapeutic strategies.