Long-term NSAID use after CRPS diagnosis associated with increased risk of peripheral neuropathy and paresthesia

Purpose: Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is common in complex regional pain syndrome (CRPS) management, but its impact on neuropathic sequelae remains unclear. This study evaluates the association between prolonged NSAID use post-CRPS diagnosis and peripheral neuropathy and paresthesia. Methods: This retrospective cohort study utilized the TriNetX Research Network to identify patients who were diagnosed with CRPS type I between January 1, 2000 and January 1, 2014. Patients were stratified by long-term NSAID use until 1 year after diagnosis. Propensity score matching (1:1) was performed, adjusting for demographics and comorbidities. Peripheral neuropathy and paresthesia outcomes were assessed 90 days and 1 year following diagnosis of CRPS. Risk ratio (RR) and 95% confidence interval (CI) were reported for significant results (P < 0.05). Results: At 90-day follow-up, there were no significant differences in the rates of paresthesia (RR: 0.985, 95% CI: 0.837–1.159) or peripheral neuropathy (RR: 1.161, 95% CI: 0.978–1.379) between patients receiving NSAIDs and controls. At 1-year follow-up, NSAID use was associated with higher rates of paresthesia (RR: 1.104, 95% CI: 0.981–1.242) and peripheral neuropathy (RR: 1.166, 95% CI: 1.023–1.328). No significant differences in paresthesia were observed at either time point. Conclusions: Despite comparable short-term outcomes, these findings show that long-term NSAID use after CRPS diagnosis is linked to a higher likelihood of developing peripheral neuropathy within 1 year. Level of evidence: Level 3, Prognostic.