The purpose of the present study was to evaluate whether a procedure confirming a nerve block at the site of herpes zoster infection by application of epidural electric stimulation was more effective in reducing pain and preventing PHN than a procedure that identifies the location of epidural catheters with contrast agents alone.
In the present study, the pain scores of patients in both tested groups were significantly lower over the 6-month follow-up period than at the baseline. From 14 days to 6 months after the procedure (follow-up period), pain scores were significantly lower in the stimulation group than in the contrast group. The odds of complete remission of herpes zoster up to 6 months after the procedure was 1.9-times higher in the stimulation group than in the contrast group. This suggests that administering the drug after confirming the correct VZV-containing dorsal root ganglion using epidural electric stimulation may be more effective in treating herpes zoster than the conventional continuous epidural infusion. The proportion of patients who received other epidural blocks because of the lack of pain control within the 6 months following the procedure, was approximately one-third lower in the stimulation group than that in the contrast group.
There was also a difference in the drug injection site of the epidural catheter tip between the two groups. Reportedly, closed-tip, multi-orifice catheters are more effective for sensory blocks than open-tip, end-hole catheters. However, in our study, the stimulation group (in which open-tip, end-hole catheters were used) showed greater pain reduction than the contrast group (in which closed-tip multi-orifice catheters were used) [14, 15]. These results suggest that a continuous epidural infusion utilizing electric stimulation to confirm the location of herpes zoster is more effective in achieving pain relief than the conventional continuous epidural infusion. EpiStim™ epidural catheters have a bent tip and a flexible guidewire and use electric stimulation to identify the affected area, increasing the maneuverability of the catheter and making it easier to position the catheter at the target site . These features yielded significant differences between the contrast and stimulation groups in our results.
In our study, there was no significant difference in pain reduction immediately after the procedure between the two groups. This is likely due to the spread of 8 mL of drug epidurally administered during the procedure. After administration, it is likely that the drug spread to adjacent dermatomes. Therefore, even if the epidural catheter was not precisely at the affected site, the drug may still have spread to the site of the herpes zoster infection, but this would occur only with a single epidural block. When the drug was administered continuously at the rate of 4 mL/h via a portable infusion pump, the spread of the drug decreased considerably. Therefore, precise administration of the drug to the correct site would have been possible only if the catheter was positioned in close proximity to the herpes zoster infection site. We suggest that the differences in pain scores at 14 days and 1, 3, and 6 months after the procedure were attributable to continued pain relief, despite reduced drug efficacy over the period of continuous administration, if the catheter was correctly placed in the target region.
Due to the complexity of the pathophysiological mechanisms that contribute to the progression of acute herpes zoster to PHN, various preventive strategies have been proposed, including vaccinations and the use of antiviral agents, anticonvulsants, and corticosteroids. However, according to a recent systematic review and meta-analysis, the efficacy of these treatments in preventing PHN is limited [16-21]. We focused on the nerve damage caused by VZV for the treatment of acute herpes zoster and PHN prevention. Reactivated VZV in the dorsal root ganglion, which manifests as herpes zoster, subsequently diffuses to the affected dermatome producing an inflammatory response and inducing nerve damage. Severe initial nerve damage or the inability to regain normal function after the loss of nerve function can lead to PHN . Therefore, proactive treatment before nerve injury can help prevent PHN. According to a recent meta-analysis, continuous epidural infusion in acute herpes zoster is effective in preventing PHN . The rationale behind the application of epidural blocks to control acute herpes zoster pain and prevent PHN is that the discontinued delivery of an invasive afferent stimulus to the central nervous system and improved flow of blood to the subjects’ nerve tissue will minimize neural damage and reduce sensitization. In addition, it is possible that local anesthetics, along with the anti-inflammatory effects of corticosteroids, could be effective in areas corresponding to the affected nerves . Epidural administration of steroids not only inhibits inflammation but also reduces deafferentation by decreasing any neural ischemia resulting from inflammatory swelling . Local anesthetics administered epidurally control pain and interfere with sensitization by blocking sympathetic nerves; however, to maximize the effects of epidural steroids and local anesthetics on the affected site, it is important to administer the drug precisely to the site of nerve injury . Therefore, we performed epidural electric stimulation to specifically identify the site sustaining the nerve injury caused by herpes zoster. This method allows for more accurate catheter placement than the conventional method, where the diffusion image of a contrast agent is used to confirm the location of the catheter.
In the current study, patients who could not maintain the inserted continuous epidural catheter for more than 10 days were excluded from the analysis because according to a previous study, a single epidural block may be effective in controlling herpes zoster-related pain, but it has limited efficacy in the prevention of PHN [25, 26].
All the patients included in our study underwent continuous epidural infusion and simultaneously took anticonvulsants and analgesics. To avoid bias due to drug treatments, patients who discontinued the drug due to side effects from other treatments and those who were administered drugs other than local anesthetics and steroids via the epidural catheter, such as opioids, were excluded from the analysis.
The complete remission rate in the present study was 51% in the contrast group and 72% in the stimulation group. Reportedly, the greater the severity of acute herpes zoster pain, the greater the likelihood of its progression to PHN [5, 27]. In our clinic, invasive treatments, such as continuous epidural infusion, are not performed for less severe cases of herpes zoster (pain score, < 4). Consequently, all the participants in the present study had pain scores of 4 or higher (mean 7.5 ± 1.5 and 7.1 ± 1.4 in the control and stimulation groups, respectively), which may be one of the reasons for the lower rates of complete remission. Additionally, the definition we adopted for complete remission (pain score of ≤ 2, no further medication prescribed) is possibly another reason for lower remission rates, since other studies have defined a pain-free state with an NRS score of less than 3, or without discussion of medication withdrawal [8, 25].
Epidural hematoma, infection, and abscess are the complications that make continuous epidural catheterization difficult, but no infections were reported after continuous epidural infusion in this study. This is likely due to the involvement of well-trained physicians who changed dressings daily and well-educated patients and caregivers. The incidence of epidural hematoma is low and was not observed in the present study. However, one patient experienced severe urinary retention after the procedure, which was resolved after the epidural catheter was removed .
First, this was a retrospective study, and there may be an influence of unmeasured confounding variables. Thus, we conducted a covariance analysis with the baseline demographics and underlying patient disease as covariates to control for potential disturbance factors. Additionally, only the patients who took both anticonvulsants and analgesics along with continuous epidural infusion were included in the study to ensure consistent drug use across the sample set.
Second, our research data were derived from electronic medical records, which may have led to an underestimation of the actual incidence of side effects. In the present study, continuous epidural infusion was discontinued in only one patient because of adverse effects, but side effects such as dysuria and motor weakness may not have been added to the medical record when the epidural block was maintained because of low symptom severity.
Third, we excluded patients who were treated with other interventional procedures within the 6-month period, and this could have caused a selection bias in the study. Nevertheless, if we had included patients who experienced other interventions in the analysis, there would have been uncertainty regarding whether the patient symptoms improved due to receiving a continuous epidural infusion for the first time, or because they had other interventions. Therefore, we excluded patients with other interventions when calculating complete remission and 6-month pain scores and analyzed the ratios separately.
Fourth, we investigated whether oral medications were administered simultaneously with continuous epidural infusion for herpes zoster, but the exact doses were not measured. The correct dose of oral medication may affect the incidence of PHN and pain in herpes zoster, which may limit the results of this study.