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Neostigmine has been found to cause peripheral analgesia. We used venous retention technique to evaluate whether neostigmine displayed peripheral analgesic effect in reducing propofol injection pain.In a double blind fashion, 105 patients were randomly allocated to receive either 1 ml 0.5 mg neostigmine (Group N, n = 35), 1 ml 2% lidocaine (Group L, n = 35), or 1 ml normal saline (Group C, n = 35) as pretreatment to reduce pain on propofol injection. A pediatric T-connector linking with the i.v. catheter port was used for injection. Venous occlusion was made possible with a tourniquet before the intravenous administration of one of the three drugs. The tested drug was allowed to retain for one minute and then the tourniquet was released for propofol injection. Pain and side effect assessments were made after propofol injection.The incidence of propofol injection pain was 85% in normal saline group, 46% in neostigmine group and 6% in lidocaine group (P0.05 among groups). The tested drugs arrayed in order of increasing magnitude of intensity of pain upon propofol injection were lidocaine (mean rank 34.20), neostigmine (mean rank 50.42) and normal saline (mean rank 76.81) in sequence (P0.05 among groups).With one-minute venous retention, 0.5 mg neostigmine (1 ml) could produce peripheral analgesia to some degree in reducing propofol injection pain. However, its analgesic effect was inferior to 1 ml of 2% lidocaine.