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Background: Chronic neuropathic pain in leprosy patients after completion of multi-drug therapy (MDT) is an under-researched problem. The reason why some leprosy patients develop it is unknown. In this study we evaluated the role of ongoing inflammation and small-fibre neuropathy as possible contributing factors for neuropathic pain., Methods: We assessed chronic neuropathic pain in 17 leprosy patients who had completed MDT and were attending a referral clinic in Hyderabad, India. All patients had a clinical assessment, intraepidermal nerve (IENF) assessment and quantitative sensory testing (QST), which included the testing of tactile and pinprick sensations using Semmes-Weinstein monofilaments and weighted needles method. Nine patients had a sural nerve biopsy (SNB)., Results: Thirteen patients had a glove and stocking pattern of neuropathy. All nerve biopsies showed inflammation with intraneural inflammation and perineural thickening, and intraneural acid fast bacilli were observed in five biopsies. IENF analysis of the skin biopsy specimens in 16/17 patients showed a statistically significant reduction in IENF density (P < 0.001, Mann Whitney test) compared to control skin biopsies. Complete depletion of intraepidermal nerves was observed in six patients. QST also showed marked abnormalities. In 11 patients total sensory loss for all modalities was found, and in the other six patients the sensory function was seriously impaired., Discussion: There is evidence of ongoing intraneural inflammation in leprosy patients who have completed MDT. This may explain the occurrence of chronic neuropathic pain. Using IENF density measurement we have found significant small-fibre neuropathy in leprosy patients and the use of this tool could be expanded.