IntroductionUremic pruritus (UP) is a common complication of end-stage renal disease that significantly impairs patients’ quality of life. Although acupuncture can effectively relieve UP symptoms, its central mechanism remains unclear.Methods and analysisA total of 96 patients with UP will be randomly assigned to three groups: verum acupuncture (VA), sham acupuncture (SA), or waiting-list (WT) control. All participants will undergo a cowhage test to induce acute itch and receive a single session of instant VA, SA, or no intervention (WT) during functional near-infrared spectroscopy (fNIRS) scanning. Subsequently, participants in the VA and SA groups will receive 4 weeks of consecutive acupuncture treatment. Hemodynamic changes in the prefrontal cortex and primary somatosensory cortex will be monitored during the instant acupuncture session, as well as after the 6th and 12th sessions of long-term acupuncture. Clinical outcomes involving itch intensity, quality of life, and psychological status will also be assessed.DiscussionThis study aims to explore the central mechanisms underlying both the immediate and long-term effects of acupuncture on UP in a real clinical setting using fNIRS. We hypothesize that VA will specifically modulate neural activity patterns in itch-related brain regions, and that these changes will correlate with clinical symptom improvement. This study will provide visual neuroimaging evidence for the antipruritic effects of acupuncture, thereby facilitating more precise acupuncture treatments for UP.Clinical trial registrationhttps://itmctr.ccebtcm.org.cn, identifier ITMCTR2025001844.