Hsieh Y-L. Reduction in induced pain by ultrasound may be caused by altered expression of spinal neuronal nitric oxide synthase-producing neurons. To examine the peripheral influence of therapeutic ultrasound (US) on central spinal nociceptive modulation. Controlled, experimental animal trial. Neuroscience laboratory of a medical university in Taiwan. Ten male Wistar rats weighing 250 to 300g. To induce inflammatory arthritis, the rats were injected intracapsularly with complete Freund’s adjuvant (CFA) into the right tibiotarsal joint. Eighteen hours later, at the inflammatory phase of arthritis, US or sham-operated treatment was applied to the arthritic limb. The numbers and distributional proportions of immunoreactive spinal neuronal nitric oxide synthase-like (nNOS-LI) neurons were assessed. The nNOS-LI neurons were abundant bilaterally in the L1 and L2 regions of the spinal cord areas after CFA-induced arthritis with sham-operated treatment. US treatment significantly suppressed this increase in the numbers of nNOS-LI neurons bilaterally in the superficial laminae (laminae I–II, P<.001), nucleus proprius (laminae III–IV, P<.01), deep laminae (laminae V–VI, P<.001), and ventral horn (laminae VII–X, P<.001) of the spinal cord. When expressed as a percentage of the total labeled cells, the proportions of nNOS-LI neurons showed significant differences in laminae III–IV (P<.001) and laminae V–VI (P<.01) between sham-treated rats and those treated with US. US treatment may modulate the CFA insult-induced increase in total and regional nNOS-LI neurons. I propose that the peripheral influences of US on central modulation of the spinal nociceptive processing system is important and may reflect the neuroplasticity of the spinal cord in response to peripheral input.