Plasma Vitamin C Is Lower in Postherpetic Neuralgia Patients and Administration of Vitamin C Reduces Spontaneous Pain but Not Brush-evoked Pain

OBJECTIVES: Plasma vitamin C concentrations have been suggested to be related to pain modulation in postherpetic neuralgia (PHN), an intractable neuropathic pain syndrome. In this study, we first compared plasma concentrations of vitamin C between healthy volunteers and PHN patients and then designed a symptom-based and mechanism-based approach to assess the analgesic effect of intravenous vitamin C on spontaneous and brush-evoked pain. METHODS: Study 1 was cross-sectional that enrolled 39 healthy volunteers and 38 PHN patients. Study 2 was a double-blinded, placebo-controlled intervention study, which comprised 41 patients randomly allocated into the ascorbate group and placebo. Each patient received normal saline infusion with or without ascorbate on days 1, 3, and 5 and answered questionnaires that included side effects; numeric rating pain scale (NRS) on spontaneous and brush-evoked pain on days 1, 3, 5, and 7; and patient global impression of change on spontaneous and brush-evoked pain on day 7. RESULTS: Study 1 revealed that plasma concentrations of vitamin C were significantly lower in patients with PHN than in healthy volunteers (P<0.001). Study 2 showed that ascorbate treatment effectively restored plasma vitamin C concentrations in the patients and decreased spontaneous pain by 3.1 in NRS from baseline to day 7, as compared with a decrease of 0.85 in NRS by placebo treatment (P<0.001). Conversely, ascorbate treatment did not significantly affect brush-evoked pain. Ascorbate treatment also resulted in a better efficacy than placebo in patient global impression of change on spontaneous pain (P<0.001) on day 7 and did not affect brush-evoked pain. No side effects were observed. CONCLUSIONS: Plasma vitamin C status plays a role in PHN, and intravenous ascorbate helps relieve spontaneous pain in PHN.