Pain management in HZ is incorrectly perceived by many clinicians as involving mild and readily treatable conditions. Treatment options remain inadequate, particularly for PHN, as the pain can have devastating effects on a patient’s Quality of Life (QoL). This pain can persist for long durations, affecting the patient’s physical and psychological health, as well as their ability to engage in normal daily and social activities [1]. The 5% lidocaine patch is very effective in managing the pain associated with PHN and other neuropathies. However, there are very few studies on the treatment of PHN with the 5% lidocaine patch in India. Keeping this in mind, the present study was conducted to evaluate the analgesic effect of the 5% lidocaine patch in PHN [2-5].
The HZ is a painful and debilitating condition caused by the reactivation of the VZV from a latent infection in sensory ganglia. The disease progression can be divided into four phases: prodrome, acute, subacute and chronic. The prodrome occurs 1-5 days before the onset of the HZ rash in 70%-80% of cases [6-8]. Acute HZ is typically defined as occurring up to 30 days after the onset of the rash. In patients who develop chronic disease, there is a subacute phase [9,10]. HZ is characterised by a maculopapular or vesicular rash, usually accompanied by pain that is unilateral and restricted to dermatomes. The acute phase subsides in days or weeks; however, in some cases, the pain persists and may develop into PHN. Pain in the acute phase can be constant or intermittent and may present with varied symptoms, such as burning or stabbing sensations, itching, tingling or numbness, squeezing sensations and a deep aching or “pulled muscle” sensation. Other predictors of PHN include the presence of prodromal pain, the intensity of the rash and the level of pain experienced [11,12].
The most prevalent consequence of HZ is PHN, defined as pain that persists for 90 days or more after the onset of the HZ rash. The VAS is commonly used to measure the pain associated with PHN [13,14]. Various modalities of chronic pain management like Non Steroidal Anti-Inflammatory Drugs (NSAIDs), opioids and local injectables, have been used. The World Health Organisation (WHO) analgesic ladder is a strategy proposed to provide adequate pain relief for neuropathic pain. The ladder mainly consists of three steps: non opioid analgesics, such as NSAIDs or acetaminophen with or without adjuvants, are used for mild pain; weak opioids with or without non opioid analgesics and with or without adjuvants are used for moderate pain; and potent opioids (morphine, methadone, fentanyl, buprenorphine, oxymorphone) with or without non opioid analgesics and with or without adjuvants are used for severe pain [15].
Lidocaine is available in various forms, including intravenous, cream, gel, intrathecal and transdermal patches, each in different concentrations. The topical 5% lidocaine medicated plaster functions in two ways: the hydrogel plaster itself provides protection, while the diffusion of lidocaine acts pharmacologically. For patients suffering from neuropathic pain, the plaster offers a mechanical barrier against stimuli that cause allodynia or hyperalgesia. The most common side-effects associated with the lidocaine patch include mild redness and skin irritation. The use of the lidocaine patch has reduced the intake of other oral analgesic medications and has been shown to be well-tolerated and safe due to its localised action and limited systemic absorption. It has been recommended as a first-line therapy for PHN as per guidelines set by the American Academy of Neurology (2004) [16-18]. The present study aimed to evaluate the analgesic efficacy of the 5% lidocaine patch in treating PHN.
Materials and Methods
The present prospective interventional study was conducted in the Department of Anaesthesiology and Critical Care, Pt. BD Sharma, PGIMS, Rohtak, Haryana, India, from February 2020 to March 2021. After the approval from Ethics Committee’s (IEC number: IEC/Th/19/Anst20) and the Clinical Trials Registry-India (CTRI) number (CTRI/2020/08/027262), informed written consent was obtained from the patients.
Sample size calculation: The sample size was determined using the VAS to compare the effectiveness of the intervention, assuming a difference of one at subsequent time points from baseline as clinically significant. Thus, a sample size of 24 patients was deemed necessary to detect statistical significance with an effect size of 0.67, an alpha level of 0.05 and a power of 90%.
The standard normal deviate for α=Zα=1.96;
The standard normal deviate for β=Zβ=1.282.
S(Δ)=Standard Deviation of the change in the outcome.
Inclusion criteria: A total of 24 patients aged 18 to 75 years, suffering from chronic pain due to PHN with a VAS score greater than 4 for at least three months and without satisfactory pain relief from conservative treatments (such as anticonvulsants, antidepressants and opioids), presenting to the pain clinic OPD, were enrolled.
Exclusion criteria: Patients with a history of severe medical illnesses, allergies to lidocaine or other local anaesthetics, pregnant or lactating females, any motor neuron diseases (such as myasthenia gravis), psychiatric disorders and those with fever were excluded from the study.
Study Procedure
All patients were examined during the OPD visit. A detailed clinical history was taken, including the duration and distribution of pain, previous medical treatments and VAS scores. General, physical and systemic examinations were performed. Patients with a VAS score greater than 4 (where 0 indicates no pain and 10 indicates severe pain) were enrolled in the study.
In addition to oral analgesic treatment (paracetamol and diclofenac), a 5% medicated lidocaine patch was applied daily to all painful areas of appropriate size for a minimum of 12 hours, after which the patch was removed. The patch was then reapplied for another 12 hours and removed again. This application continued until the VAS score declined to 4 or for a maximum follow-up period of four weeks. However, patients were followed-up beyond the study period.
An evaluation of patient pain using the VAS was conducted before the application of the patch and after 1, 2, 3 and 4 weeks of patch application. The total number of patches used per week for four weeks or until the VAS score declined to 4 was recorded. The primary objective of the study was to assess the VAS score before and after the application of the lidocaine patch. The secondary objective was to monitor side-effects such as allergies, redness, itching, etc., and to manage them accordingly.
Statistical Analysis
After coding, the data was entered into a Microsoft Excel spreadsheet. Data analysis was conducted using Statistical Package for the Social Sciences (SPSS) version 20 (IBM SPSS Statistics Inc., Chicago, Illinois, USA) on a Windows software program. A repeated measures Analysis of Variance (ANOVA) was used to compare quantitative data across all clinical indicators. The repeated measures ANOVA is a research design that involves multiple measures of the same variable taken on the same or matched subjects, either under different conditions or over two or more time periods. The level of significance was set at p≤0.05.
Results
The demographic profile of patients according to age and gender is illustrated in [Table/Fig-1]. It shows that the maximum number of patients falls within the age group of 60-70 years. Out of 24 patients, 11 were males (45.8%) and 13 were females (54.2%), indicating that with increasing age, there are more male patients. The mean age was 59.5±12.85 years. No statistical differences were observed in the demographic profile.
Age and gender-wise distribution of patients.
| Age groups (years) | Gender | Total n (%) |
|---|
| Female n (%) | Male n (%) |
|---|
| 30-40 | 2 (66.7) | 1 (33.3) | 3 (100.0) |
| >40-50 | 3 (100.0) | 0 | 3 (100.0) |
| >50-60 | 3 (60.0) | 2 (40.0) | 5 (100.0) |
| >60-70 | 3 (42.9) | 4 (57.1) | 7 (100.0) |
| >70 | 2 (33.3) | 4 (66.7) | 6 (100.0) |
| Total | 13 (54.2) | 11 (45.8) | 24 (100.0) |
The VAS score at baseline was 8.71±0.999, which reduced to 3.58±0.830 at the end of four weeks (p=0.001). A statistically significant reduction in the VAS score was noted at 1, 2, 3 and 4 weeks [Table/Fig-2].
Represents reduction in VAS score from baseline (day 1).
| Time interval | Minimum-Maximum (VAS) | Mean±Std. Deviation | p-value |
|---|
| Day 1 | 7-10 | 8.71±0.999 | 0.001 |
| 1 weeks | 5-9 | 7.08±1.349 |
| 2 weeks | 4-7 | 5.67±1.007 |
| 3 weeks | 4-5 | 4.25±0.442 |
| 4 weeks | 2-4 | 3.58±0.830 |
Repeated measures ANOVA test
There were statistically significant differences in the VAS scores over the four weeks, with a p-value <0.01 [Table/Fig-3].
VAS at different interval from base line. Mean VAS, at the end of each week beginning from day 1.
| Time interval | Mean difference | p-value |
|---|
| Day 1 | 1 weeks | 1.625* | 0.001 |
| 2 weeks | 3.042* | <0.01 |
| 3 weeks | 4.458* | <0.01 |
| 4 weeks | 5.125* | <0.01 |
| 1 weeks | Day 1 | -1.625* | 0.001 |
| 2 weeks | 1.417* | 0.001 |
| 3 weeks | 2.833* | <0.01 |
| 4 weeks | 3.500* | <0.01 |
| 2 weeks | Day 1 | -3.042* | <0.01 |
| 1 weeks | -1.417* | 0.004 |
| 3 weeks | 1.417* | 0.004 |
| 4 weeks | 2.083* | <0.01 |
| 3 weeks | Day 1 | -4.458* | <0.01 |
| 1 weeks | -2.833* | <0.01 |
| 2 weeks | -1.417* | 0.004 |
| 4 weeks | 0.667 | 0.19 |
| 4 weeks | Day 1 | -5.125* | <0.01 |
| 1 weeks | -3.500* | <0.01 |
| 2 weeks | -2.083* | <0.01 |
| 3 weeks | -0.667 | 0.19 |
Repeated measures ANOVA test
The number of patches used in the first week was 1.88±0.338, which reduced to 1.00 by the fourth week [Table/Fig-4]. Total amount of patches was reduced significantly over 1, 2, 3, and 4 weeks (p-value=0.001) shown in [Table/Fig-5].
Represents total number of lidocaine patch used per weeks.
| Time interval | Minimum-Maximum | Mean±Std. Deviation | p-value |
|---|
| Day 1 | 0 | 0.00±0.000 | 0.001 |
| 1 week | 1-2 | 1.88±0.338 |
| 2 weeks | 1-2 | 1.46±0.509 |
| 3 weeks | 1-2 | 1.04±0.204 |
| 4 weeks | 1 | 1.00±0.000 |
Repeated measures ANOVA test
Mean number of patches used at different time intervals from baseline (day 1) to end of each week.
| Time interval | Mean difference | p-value |
|---|
| Day 1 | 1 weeks | -1.875* | <0.01 |
| 2 weeks | -1.458* | <0.01 |
| 3 weeks | -1.042* | <0.01 |
| 4 weeks | -1.000* | <0.01 |
| 1 weeks | Day 1 | 1.875* | <0.01 |
| 2 weeks | 0.417* | <0.01 |
| 3 weeks | 0.833* | <0.01 |
| 4 weeks | 0.875* | <0.01 |
| 2 weeks | Day 1 | 1.458* | <0.01 |
| 1 weeks | -0.417* | <0.01 |
| 3 weeks | 0.417* | <0.01 |
| 4 weeks | 0.458* | <0.01 |
| 3 weeks | Day 1 | 1.042* | <0.01 |
| 1 weeks | -0.833* | <0.01 |
| 2 weeks | -0.417* | <0.01 |
| 4 weeks | 0.042 | 0.45 |
| 4 weeks | Day 1 | 1.000* | <0.01 |
| 1 weeks | -0.875* | <0.01 |
| 2 weeks | -0.458* | <0.01 |
| 3 weeks | -0.042 | 0.45 |
Repeated Measures ANOVA test
No local side-effects (such as itching or eczema) were observed in any of the patients. All patients expressed satisfaction with the treatment allocated for pain management.
Discussion
Acute herpetic neuralgia is a painful condition that is almost always experienced by patients suffering from HZ. Acute herpetic neuralgia typically subsides within days or weeks; however, some patients continue to experience pain beyond three months. Traditional treatments have included anticonvulsants, opioids and tricyclic antidepressants, but these agents are associated with adverse systemic effects. This has led to the development of the 5% lidocaine patch, a newer and potentially safer option [19].
Lidocaine is a well-established voltage-gated sodium channel inhibitor that blocks specific sodium channels within the dermal nociceptors of A-delta and C fibres. By reducing ectopic discharges, this blockade alleviates pain. Additionally, lidocaine inhibits inflammation, suppresses nitric oxide production and regulates T-cell activity [20]. It may also activate the Transient Receptor Potential (TRP) channels in such a way that it depolarises the membranes and produces an analgesic effect by reducing electrical activity in nerves containing TRP channels. The application of the 5% Lidocaine Medicated Patch (LMP) typically produces an initial soothing and cooling “patch effect” [21].
In the present study, the authors enrolled 24 patients of either sex for four weeks, using a 5% lidocaine patch by using VAS scale. At the end of the first week, the VAS score had significantly decreased (p=0.001). In subsequent weeks, compared to day 1, there was a decline in the VAS score from a mean of 8.71±0.999 on day 1 to a mean of 3.58±0.830 at four weeks. No side-effects were observed in any of the patients.
Argoff CE et al., conducted an open-label, non randomised, prospective study that included 77 patients {n=8 of PHN, n=41 with DN and n=28 with Lower Back Pain (LBP)} for two weeks, using the NPS with a 5% lidocaine patch. For patients with PHN (n=8; p<0.01), the 5% lidocaine patch showed a numerical advantage across all four Neuropathic Pain Scale (NPS) composite measures. It also significantly improved symptoms for patients with uncomfortable DN (n=41; p<0.001) and LBP (n=28; p≤0.005). Overall, 8 patients (10%) experienced mild to moderate side-effects from their treatment. The study concluded that moderate to severe chronic pain resulting from PHN, DN and LBP can be effectively reduced by the 5% lidocaine patch. We obtained similar results to those of Argoff CE et al., regarding the reduction of VAS/NPS scores, with no side-effects reported [2].
In the present study, the authors evaluated a total of 24 patients, with a mean age of 59.5±12.85 years. Among them, 54.2% were female and 45.8% were male. They found a significant reduction in the VAS score, which decreased from 8.71±0.999 to 3.58±0.830 (p<0.001). Additionally, they assessed the total number of patches consumed from baseline to 4 weeks. The mean number of patches used at one week decreased from 1.88±0.388 to 1.00 by the end of four weeks (p<0.001). This indicates that the painful area decreased over time with the use of the lidocaine patch.
Nalamachu S et al., conducted a study involving 332 patients, comprising 59.5% female and 40.5% male participants [3]. The mean age of patients suffering from PHN was 73.4 years for those with pain localised to the head dermatome, 70.6 years for the trunk and 76 years for the extremities. In their study, the Brief Pain Inventory (BPI) was used over four weeks with the application of a 5% lidocaine patch. The results showed that BPI scores decreased on the head dermatome from 7.0 (2.1) to 4.7 (2.7), representing a pain relief of 34.8%. For the trunk dermatome, scores decreased from 7.4 (2.0) to 5.5 (2.5), with a pain relief of 36.8%. On the extremities, scores decreased from 7.0 (2.1) to 5.2 (2.9), resulting in a pain relief of 19.5%. Average pain improved significantly from baseline by 1.05 to 2.04 (p<0.002) in each of the three anatomical areas, with no significant differences in effectiveness based on patch location.
Both studies concluded that the 5% lidocaine patch is effective in reducing pain and the painful area [3].
In the present study, the authors included 24 patients, 11 male and 13 female only of PHN for four weeks and VAS was reduction, with p<0.001 at the end of the four weeks and no adverse effects were observed.
Martini A et al., conducted a study involving 130 patients (86 male and 44 female) with a mean age of 65.5 years, using the VAS scale for a 12-month follow-up in cases of PHN and trigeminal neuralgia. During the follow-up, 15% of patients achieved complete pain relief without any systemic therapy (p<0.009) and 38% of patients reduced their analgesic drug consumption, with the highest reduction seen in those with radiculopathy. The most significant decrease was observed in the first month of therapy, with p<0.009 after one month and p<0.001 after 12 months. Some topical and transient adverse effects, such as itching or local erythema, were reported in 14.6% of patients and 5.4% needed to discontinue treatment due to adverse effects. The present study concluded that, in cases of localised neuropathic pain, LMP treatment is safe and merits consideration as an adjunctive treatment to reduce the need for analgesic medications. Both studies concluded that the 5% lidocaine patch is very effective in reducing neuropathic pain [4].
In the present study, the mean VAS scale reduced from day 1, with a value of 8.71±0.999, to 7.08±1.34 at the end of the first week, 5.67±1.007 at the end of the second week, 4.25±0.442 at the end of the third week and 3.58±0.830 at the end of the fourth week (p<0.001). The total number of patches used at the end of the first week was 1.88±0.388, which decreased to 1.46±0.509 at the end of the second week, 1.04±0.204 at the end of the third week and 1.00 at the end of the fourth week (p<0.001). This indicates that the painful area decreases over time with the use of the lidocaine patch.
Bianchi L et al., conducted a study on 38 patients with acute neuralgia and PHN using the DN4 and NRS-11 scales for eight weeks with a 5% lidocaine patch [5]. The effectiveness of the lidocaine patch was documented in 31 patients at two weeks and in all patients at four and eight weeks. The effectiveness of the 5% lidocaine patch was noted in 31 patients (81.6%; acute neuralgia group: 89.5%; PHN group: 73.7%; p=0.236) at week 2 and in all patients at weeks 4 and 8. The total number of responders was 4 (10.5%), 14 (35.9%) and 18 (46.2%) at weeks 2, 4 and 8, respectively and was more frequent in the acute neuralgia group (12/19, 63.2%) than in the PHN group (6/19, 31.6%) (p=0.054).
The average number of 5% lidocaine patches utilised from the beginning of the study to week 8 was similar in both the acute neuralgia and PHN groups (41.8 and 41.5, respectively) and decreased progressively (week 2: 0.99 patches/day; week 4: 0.98 patches/day; week 8: 0.74 patches/day), without significant differences between the two groups. This study concluded that starting the lidocaine patch as early as possible in acute neuralgia patients ensures rapid pain relief and reduces the need for systemic analgesics. Furthermore, early treatment onset seems to help prevent PHN.
From both studies, the authors concluded that the lidocaine patch significantly reduced pain and the painful area, leading to a decreased consumption of lidocaine patches over time [5].
Limitation(s)
The limitations of the present study included a small sample size due to a lack of patients in the outpatient department during Coronavirus Disease 2019 (COVID-19). Additionally, the authors only included cases with a single dermatome distribution of PHN and enrolled patients without any co-morbid conditions. For future studies, the authors recommend using a larger sample size, conducting multicentric research, studying PHN in areas affected by more than one dermatome and including patients with co-morbid conditions.
Conclusion(s)
The 5% lidocaine patch demonstrated good tolerability with minimal risk of systemic adverse drug reactions and is an effective modality for relieving moderate to severe pain. After completing the study, authors concluded that the local application of the 5% lidocaine patch is very effective in treating PHN without any side-effects and results in high patient satisfaction. Patient satisfaction encompasses various aspects, including general satisfaction with medical care, communication, interpersonal manner, technical quality and financial considerations.
Repeated measures ANOVA testRepeated measures ANOVA testRepeated measures ANOVA testRepeated Measures ANOVA test