Movement is changed in pain, but the mechanisms remain unclear. Key questions are unresolved such as whether activation can be inhomogeneously distributed within a muscle in a manner that is specific to the location of noxious input. This study addressed this question using high-density electromyography (EMG) to study regional redistribution of muscle activation within the vasti muscles and changes in knee extension force direction in response to noxious stimulation applied to muscular and nonmuscular tissues around the knee. Fourteen participants performed a low-force knee extension contraction at baseline, during, and after pain induced in 4 locations (infrapatellar fat pad, vastus lateralis, distal vastus medialis, or proximal vastus medialis). The knee extension force direction was estimated from a 3-dimensional load cell positioned just above the ankle. Regional muscle activation was estimated from amplitude of high-density surface EMG signals from vastus medialis and lateralis. Pain-induced spatial variations of activation were identified as the position of the 5 channels that showed the largest decrease (or smallest increase) in amplitude from baseline to pain or after pain. Knee extension force was produced more medially during pain after infrapatellar pad injection only (P = 0.01). Preferential reduction of activation of the distal region of vastus medialis was observed when distal vastus medialis (P < 0.001) or vastus lateralis (P < 0.05) was injected. Both adaptations persisted after pain resolution. These results support the hypothesis that specific adaptation depends on the location of a noxious stimulus and imply that recovery of pain is not necessarily concomitant with return of the EMG to prepain patterns.