Chronic pruritus of unknown origin (CPUO) is defined as itching lasting more than 6 weeks in the absence of discernible skin lesions. Pregabalin is used to treat patients with CPUO. In this study, we aimed to investigate differences in the perception threshold of itch sensation between patients with CPUO and healthy individuals and to evaluate the efficacy of pregabalin for CPUO. At baseline, week 2, and week 4 after treatment initiation, the visual analogue scale (VAS) score was measured to assess pruritus severity, and electric current perception threshold (CPT) was measured at 250 and 5 Hz using a NEUROMETER CPT/C stimulator. Twenty healthy individuals and 41 patients with CPUO were enrolled in this study. The patients with CPUO were categorised as those who responded to antihistamines (Antihistamine group), were not improved by antihistamines (Pregabalin group), and were not improved by antihistamines and pregabalin (Refractory group). The baseline CPT values were not significantly different between patients with CPUO and healthy control. Pruritus was improved in 7 of 10 patients in the Pregabalin group after treatment with pregabalin, showing decreased CPT at 5 Hz. The sensitive C-fibres presented a high threshold to detect itch sensation, and this sensitivity decreased in response to treatment with pregabalin. Chronic pruritus is defined as itching that persists for more than 6 weeks 1. Chronic pruritus of unknown origin (CPUO) refers to the condition where such itching occurs in the absence of known disease processes 2,3. Given that patients with CPUO often fail to respond to topical treatments and oral antihistamines, gabapentin or pregabalin, which are used to treat neuropathic pain 4 , have been increasingly used because CPUO and neuropathic pain are associated with a similar involvement of the nervous system 5. Measurement of the electric current perception threshold (CPT) is based on the detection of the threshold of sensory nerves to electric stimulation 6. NEUROMETER CPT⁄C (Neurotron Inc., Baltimore, MD, USA) measures the CPT at frequencies of 2,000, 250, and 5 Hz, which are the sensory thresholds of Aβ-, Aδ-, and C-fibres, respectively 6 , of which Aδ-and C-fibres are considered to transmit itching signals from the skin 7. To the best of our knowledge, no study has evaluated the CPT in patients with CPUO during pregabalin treatment and compared their baseline data with those of healthy people. Therefore, we attempted to confirm, using the visual analogue scale (VAS) and CPT, the effect of pregabalin on patients with CPUO who were unresponsive to topical steroids and oral antihistamines. We also investigated whether there are any differences in the CPT between patients with CPUO and healthy individuals. Methods Study participants. Eligible participants were adults with chronic pruritus that persisted for more than 6 weeks and healthy individuals as the Healthy control group. Patients with chronic pruritus had thorough history taking, physical examination, and laboratory tests, including tests for cr...