Toomey, DavidLewis, GwynRashid, UsmanTuck, NatalieRice, David2026-05-252026-05-252026-03-03Neuromodulation, ISSN: 1094-7159 (Print); 1525-1403 (Online), Wiley, S1094-7159(26)00023-1-. doi: 10.1016/j.neurom.2026.01.0111094-71591525-1403http://hdl.handle.net/10292/21207BACKGROUND: Exercise induces short-term pain relief (exercise-induced hypoalgesia, EIH), but this response is often blunted in people with knee osteoarthritis (OA). Transcranial direct current stimulation (tDCS) has been proposed as a potential enhancer of EIH. OBJECTIVE: This study aimed to determine whether a single session of 2-mA anodal tDCS applied for 20 minutes over the contralateral primary motor cortex augments the exercise-induced hypoalgesic response to isometric quadriceps exercise in individuals with knee OA. MATERIALS AND METHODS: In this double-blind randomized cross-over trial, 27 participants with knee OA completed two experimental sessions (active anodal tDCS + exercise; sham tDCS + exercise) in counterbalanced order. Pressure pain thresholds (PPTs at the knee and forearm), resting knee pain, and evoked knee pain during stepping were assessed pre- and post intervention. Linear mixed models compared pre- and postexercise changes between active and sham conditions. Blinding success was evaluated using Bang's blinding index. RESULTS: Both sessions produced EIH (knee PPT increased pre-to-post; all p ≤ 0.001). Between active and sham conditions, there were no significant differences for knee PPT (mean difference 0 kPa [95% CI -50 to 40], p = 0.82), forearm PPT (-20 kPa [-60 to 30], p = 0.45), resting knee pain (1/100 [-13 to 15], p = 0.89), or evoked knee pain (1/100 [-7 to 8], p = 0.14). Blinding was successful, and no adverse events were reported. CONCLUSIONS: These findings indicate that a single session of anodal tDCS does not augment the immediate EIH response to isometric quadriceps exercise in people with knee OA. PERSPECTIVE: This randomized cross-over trial found that anodal tDCS did not enhance EIH in people with knee OA. These findings suggest that a single session of anodal tDCS does not meaningfully augment the immediate exercise-induced hypoalgesic response in individuals with knee OA. CLINICAL TRIAL REGISTRATION: The Australian New Zealand Clinical Trials Registry number for the study is ACTRN12621000787886, registered July 1, 2021, prospectively.© 2026 The Authors. Published by Elsevier Inc. on behalf of the International Neuromodulation Society. This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. You are not required to obtain permission to reuse this article.https://creativecommons.org/licenses/by/4.0/Clinical trialexercise-induced hypoalgesiaknee osteoarthritispaintranscranial direct current stimulation32 Biomedical and Clinical Sciences3202 Clinical SciencesRehabilitationArthritisPhysical ActivityNeurosciencesClinical Trials and Supportive ActivitiesAgingPain ResearchChronic PainOsteoarthritisClinical Research6.3 Medical devicesMusculoskeletal1103 Clinical Sciences1109 Neurosciences1702 Cognitive SciencesNeurology & Neurosurgery3209 NeurosciencesJournal ArticleOpenAccess10.1016/j.neurom.2026.01.011