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Objective: This randomized clinical trial investigated if the application of percutaneous electrolysis (PE) enhances endogenous pain mechanisms (EPM) when compared with a simple needle application (acting as sham)., Methods: Forty-six asymptomatic subjects, aged 18-40 years, were randomized into three groups receiving a single ultrasound-guided PE intervention consisting of a needle insertion on the lateral epicondyle: sham (without electrical current), low-intensity (0.3 mA, 90s), or high-intensity (three pulses of 3 mA, 3s) PE. Widespread pressure pain thresholds (PPT), conditioned pain modulation (CPM), and temporal summation (TS) were bilaterally assessed in the lateral epicondyle, bicipital groove, transverse process of C5 and tibialis anterior muscle. Outcomes were obtained by an assessor blinded to the treatment allocation of the subjects., Results: No significant changes in CPM were observed in either group (omnibus ANOVA all, P > .05). A significant bilateral increase in PPT in the lateral epicondyle in the high intensity group as compared with the sham group was observed (P < .01). A significant decrease of TS in both low (P = .002) and high (P = .049) intensity groups on the right, but not on the left, tibialis anterior was also observed when compared with the sham group., Conclusions: One session of PE is able to slightly stimulate modulatory pathways related to nociceptive gain, particularly pressure pain sensitivity and temporal summation but not conditioning pain modulation, when compared with a sham needle intervention, with changes even contralaterally. No significant differences were found between low- and high-intensity doses of percutaneous electrolysis., (Copyright © 2023 Elsevier Ltd. All rights reserved.)