Abstract:As a second-generation voltage-gated calcium channel α2-δ subunit modulator, pregabalin has emerged as a first-line fundamental agent for the management of neuropathic and nociplastic pain. This article systematically summarizes its mechanism of action, pharmacokinetic advantages, and significant clinical research findings in conditions such as postherpetic neuralgia, painful diabetic peripheral neuropathy, and fibromyalgia. Despite its multidisciplinary application advantages characterized by rapid onset and established efficacy, current clinical practice still faces several unresolved issues: limited response rates to monotherapy in some complex and refractory pain cases; dose-dependent adverse events (e.g., somnolence, dizziness) that restrict adequate dosing in special populations; and a lack of objective criteria to guide individualized medication. To address these challenges, future development directions and work goals should focus on: 1) exploring objective predictive biomarkers to shift from a "trial-and-error" approach to "precision analgesia"; 2) deepening research on the synergistic mechanisms and optimized strategies of combining pregabalin with minimally invasive neuromodulation (e.g., spinal cord stimulation); 3) accelerating the translational application of novel topical delivery systems (e.g., transdermal gels, microneedles) to minimize off-target effects; and 4) establishing long-term continuous management guidelines relying on large-sample real-world data. In conclusion, overcoming these academic and clinical bottlenecks will further expand the application potential of pregabalin and comprehensively enhance long-term benefits for patients with chronic pain.
