Intravenously administered ascorbic acid did not relieve acute herpes zoster (HZ) pain; but is effective for reducing the incidence of postherpetic neuralgia (PHN).

After the primary varicella-zoster virus infection, there is an occurrence of acute skin disease called herpes zoster (HZ). Within the dorsal root ganglia, the virus remains latent and becomes re-energized by the factors lessening the cell-mediated immunity, traveling down the sensory root ganglia to cause acute pain and vesicular eruption. Herpes zoster can cause pain during the acute phase and results in various complications including postherpetic neuralgia (PHN), encephalomyelitis, and neural paralysis, even after treatment. Postherpetic neuralgia persists for 1 to 6 months even after improvement in cutaneous outbreak. Its occurrence differs with definition, ranging from 8%∼15%. It significantly impairs the patient’s quality of life because of physical disability and mental disorders. The treatment of HZ aims to a quick recovery of skin lesions, reduction in the intensity and duration of acute pain, and decreasing the frequency of problems like PHN. Antiviral drugs, analgesic drugs, lower level laser therapy, and preventive vaccines are used as a conventional approach for acute pain and PHN; while the treatment of HZ remains a challenge. Vitamin C deficiency has been marked in patients with viral infections and has been found to play an important role in the pathogenesis of herpes infection and incidence of PHN. Various studies have confirmed the positive effects with the intravenous (IV) injection of vitamin C in treating acute pain from HZ and PHN. However, arguments continue about the suitability of using vitamin C in the treatment of HZ.

Rationale behind research:

• In South Korea, the idea of IV injection of vitamin C for patients with HZ remains questionable
• So, this study was conducted with a dose 5 g of vitamin C injection for every two days and the therapeutic effects of IV injection of Vitamin C in patients diagnosed with HZ and hospitalized

Objective:

To evaluate the efficacy of intravenously administrated vitamin C on acute pain and its preventive effects on PHN in patients with HZ.

NOTE: Patients who received any antiviral medications from a different hospital and were discharged within 5 days, took analgesic anti-inflammatory drugs to control pain before admission, or were not followed-up after discharge were excluded.

Study outcomes:

• Pain Intensity: Visual analogue scale (VAS) score was used on the first, second, third, fourth, and fifth days of admission and second, fourth, eight, and sixteenth week of follow-up to measure pain intensity, which was assessed using a scale of 10 (most painful) to 0 (no pain), depending on the subjective evaluation of patients. Pain intensity at the given time interval was also compared between the two groups.
• PHN: It was defined as a pain score ＞30% of the first pain score, even after 4 weeks of developing skin rash , and the occurrence was evaluated 4 weeks after the hospitalization. Age, sex, underlying diseases, time interval of skin lesions (＜72 or ≥72 hours) and pain (＜5 or ≥5 days) until treatment, involved dermatome, and incidence of PHN were compared between the vitamin C treatment group and the control group.
  

Outcomes

• The pain was decreased over time in the both groups. In particular, the pain score measured on the eighth week in the vitamin C treatment group significantly differed from that in the control group. The pain score was 1.0 for the vitamin C treatment group and lower than 2.01 for the control group. A statistically significant difference was found between the two groups even on the last week (P＜0.001). The pain score for the vitamin C treatment group (0.64) was lower than that for the control group (1.98) by 1.34 points. Changes in pain score with respect to time were statistically significant between the vitamin C treatment and control groups. Generally, the pain for the control group was scored low in the early part but increased after the second week of follow up, whereas, the pain score in the vitamin C treatment group was continuously decreased.
• The difference in pain score by age, sex, time interval of pain and skin lesions until treatment, and underlying diseases with respect to time in the vitamin C treatment group were compared. All of the analyses showed significant differences in pain score with respect to time in general (P＜0.001).  No significant change in pain score with respect to time was observed between the two age groups. However, a significant difference in pain score with respect to time was observed between sexes. Pain score decreased in both male and female groups until measured on day 4 of admission, but the pain score for the females slightly increased on the fifth days unlike male. However, after the 2 weeks of follow up, the pain score for the females continuously decreased (from 2.0±0.4 to 1.2±0.3 to 0.9±0.2 to 0.5±0.1), exhibiting a lower pain score than that for males (from 2.4±0.5 to 2.1±0.5 to 1.2±0.3 to 0.9±0.2). No significant changes in pain score was observed according to time interval of pain and skin lesion until treatment and underlying diseases.
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Figure 1: Changes in the severity of pain between Vitamin C treatment group and control group

The study results showed that the incidence of PHN was significantly decreased in vitamin C treatment group. Unlike previous reports, no significant change in acute pain within 4 weeks of hospitalization was observed between the vitamin C treatment and control groups, when pain score was compared according to time intervals. However, statistically significant differences were observed after the eighth week and continued thereafter.

Consistent with previous studies, it was found that low-dose of vitamin C was efficient in the treatment of PHN. As this study involved patients treated with IV antiviral therapy, it can be considered that antiviral treatment may offset the effect of vitamin C. Moreover, changes in overall pain with respect to time showed statistically significant difference between the two groups, and pain was more effectively controlled in the vitamin C treatment group than in the control group. In the vitamin C treatment group, changes in the pain score over time by all variables without sex did not show statistically significant differences. The women showed significant decrease in pain score. Perhaps, the more they are sensitive to pain at first, they are considered more responsive to the treatment.

In this study, the results did not reflect a significant decrease in acute pain, unlike previous studies, but the treatment was effective in preventing PHN. Also, because of the significant changes in pain over time, we argue that this may be a safe treatment for prevention of PHN and HZ-related pain without major side effects.