It is not clear whether segmental innocuous stimulation has a stronger analgesic effect than segmental noxious stimulation for chronic pain and whether the fading of current sensation during treatment interferes with the analgesic effect, as suggested by the gate control theory. Electrical stimulation (by way of Interferential Current) applied at the pain area (segmental) was administered to 4 groups of patients with osteoarthritis (OA) knee pain. Two groups were administered with noxious stimulation (30% above pain threshold) and two with innocuous stimulation (30% below pain threshold). In each group half of the patients received a fixed current intensity while the other half raised the intensity continuously during treatment whenever fading of sensation was perceived. Group 5 and 6 received sham stimulation and no treatment, respectively. The outcome measures were: chronic pain intensity, morning stiffness, range of motion (ROM), pain threshold and % pain reduction. Both noxious and innocuous stimulation significantly decreased chronic pain (P<0.001) and morning stiffness (P<0.01) and significantly increased pain threshold (P<0.001) and ROM (P<0.001) compared with the control groups. Nevertheless, noxious stimulation decreased pain intensity (P<0.05) and increased pain threshold (P<0.001) significantly more than innocuous stimulation. No differences in treatment outcomes were found between adjusted and unadjusted stimulation. (a) Interferential current is very effective for chronic OA knee pain, (b) segmental noxious stimulation produces a stronger analgesic effect than segmental innocuous stimulation, (c) the fading of sensation during treatment, does not decrease the analgesic effect. Possible mechanisms explaining the findings are discussed.