Background The Ehlers-Danlos syndromes (EDS) are a collection of heritable connective tissue disorders. Local anesthetic resistance is commonly reported by patients with EDS, but there is little clinical evidence to support this finding. We hypothesized that patients with EDS would have increased anesthetic resistance using lidocaine compared with healthy controls. Methods An interventional study design was used. Participants (total N=135: EDS n=91, healthy n=44) completed a series of sensation tests using a standardized 10 g monofilament following subcutaneous injection with saline or lidocaine at two separate sites on the right forearm in a randomized order. Participants rated their sensation at each site relative to non-anesthetized skin. Sensation was used as a surrogate measure of anesthetic effect. Participant ratings were converted into two measures: (1) a dichotomous variable to represent adequate anesthesia and (2) a delta sensation score. This study was registered on ClinicalTrials.gov ( NCT05603741 ). Results Delta sensation scores were not different at 5 min post-injection between EDS and healthy participants (p=0.2), but were significantly different at 15 min (1 (0–2) arbitrary units (a.u.) vs 2 (1–2) a.u; p=0.002) and 30 min (1 (0–2) a.u. vs 2 (1–2) a.u.; p=0.003) post-injection. There was no difference in categorical “anesthesia” at 5 min between EDS and controls (p=0.2). A smaller proportion of EDS experienced “anesthesia” at 15 min (60% vs 84%, p=0.006) and 30 min (53% vs 80%, p=0.003) post-injection compared with healthy controls. Conclusion Patients with EDS experienced increased sensation with lidocaine, suggesting shorter duration of effect of lidocaine local anesthetic. This evidence validates previous patient reports and small case studies suggesting this phenomenon. Healthcare providers should be aware of this reduced effectiveness experienced by patients with EDS, to adjust care accordingly. Trial registration number NCT05603741 .
Dunn et al. (2026) studied this question.