Treating chronic and stimulus-evoked hyperalgesia via tFUS stimulation to specific pain processing brain circuits. The conceptual diagram illustrates the hypothesis of treating chronic and stimulus-evoked hyperalgesia through tFUS stimulation in a humanized mouse model of chronic pain in SCD (HbSS-BERK). The modulation of pain-associated behaviors, such as amelioration or deterioration, is proposed to be achieved by selectively stimulating specific pain-processing brain circuits. This is facilitated using a 128-element highly focused random array ultrasound transducer capable of a dynamic focus steering in HbSS-BERK mice. The diagram captures the idea of targeted neuromodulation to influence pain responses in the context of SCD.