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ORIGINAL ARTICLE Table of Contents  
Ahead of print publication
Effect of botulinum toxin injection on pain severity and quality of life among patients with postherpetic neuralgia


1 Department of Dermatology, Venereology and Leprosy, Shadan Institute of Medical Sciences, Peeramcheru, India
2 Senior Consultant Neurosurgeon, Continental Hospital Nanakramguda Gacchibowli, Hyderabad, Telangana, India

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Date of Submission03-Apr-2022
Date of Decision19-Jun-2022
Date of Acceptance24-Jun-2022
Date of Web Publication21-Sep-2022
 

  Abstract 

Background: Herpes zoster and postherpetic neuralgia (PHN) results from reactivation of varicella-zoster virus. Pain increases sharply with advancing age and the elderly are more inclined to suffer. If herpes zoster is not treated early, patients may develop PHN. For some, it can persist for 1–2 years. Botulinum toxin injection (BTX-A) has been useful for patients suffering from PHN pain. Objective: The objective of this study was to study the effect of botulinum toxin on pain severity and quality of life in patients with PHN. Methods: A hospital record-based follow-up study was carried out among 30 PHN patients treated with hypodermic injection of BTX-A. Before injection, we measured Visual Analog Score (VAS) for pain severity and the Quality of Life (QOL) Scale using short form survey-36 (SF-36) score. BTX-A injections were given, and patients were followed every month for 6 months. During follow-up, VAS, QOL, pain frequency, and analgesic use were measured. Results: Majority were 60–69 years (40%). The proportion of males and females was not much different. Mean pain severity reduced significantly from 8.9 to 5.8 at 6 months. QOL improved significantly in 6 months. Pain frequency decreased significantly from 22.33 to 18.56 at 6 months. Mean analgesics use was 87.43 which reduced significantly to 7 at 2 weeks after BTX-A and then slowly increased to 7.66 at 4 weeks, to 8.23 at 12 weeks, and 10.4 at 24 weeks. Conclusion: Using BTX-A for treating PNH is promising and gives long-lasting results. It can be considered a valid approach in the treatment of PNH, especially in nonresponsive patients.

Keywords: Botulinum toxin, cure, pain, postherpetic neuralgia


How to cite this URL:
Prasuna R, Aeerabolli AR. Effect of botulinum toxin injection on pain severity and quality of life among patients with postherpetic neuralgia. APIK J Int Med [Epub ahead of print] [cited 2022 Oct 6]. Available from: https://www.ajim.in/preprintarticle.asp?id=356505



  Introduction Top


Herpes zoster and postherpetic neuralgia (PHN) result from reactivation of varicella-zoster virus. Pain increases sharply with advancing age and the elderly are more inclined to suffer. If herpes zoster is not treated early, patients may develop PHN. PHN is the most commonly occurring complication after the infection of the herpes zoster. It has been estimated that the incidence of PHN among patients of age more than 50 years is about 12.5%. As the age increases, the incidence of PHN also increases.[1]

It has been estimated that the range of incidence of herpes zoster is 3–5 per thousand person years and it is 5%–30% in adults aged 50 years and above.[2] It has been estimated that the incidence can be 3–10 per thousand person years in Asia-Pacific region with an increase after the age of 40 years.[3] The incidence of PHN increases from 10% in the fourth decade of life to 20%–50% among 60 years and above. It is said to be rare in young adults of age >30 years.[4],[5]

Males are less affected than females.[6] Other risk factors of PHN apart from increasing age are how severe is the acute herpes zoster, eye involvement, etc.[7]

Skin and nerve fibers are commonly affected in PHN. A continuous burning sensation is the hallmark symptom of PHN. The patients also experience a stabbing sensation. Even slight touch acts as a triggering factor for pain in such cases. Routine analgesics usually are not sufficient for relief of the pain. As the pain is severe, the quality of life of the patients is affected leading to the lowest possible quality of life.[8]

Control of symptoms is the mainstay of therapy in patients with PHN. There are many options available for these cases which can relieve the pain of PHN. However, there is a lack of therapy that can modify the disease. Commonly used oral drugs are gabapentin, pregabalin, carbamazepine, opioids, and antidepressants. However, the patient may not get relieved of the pain effectively. Moreover, these drugs produce adverse reactions on long-term use including dependence.[9],[10]

The organism, Clostridium botulinum produces the botulinum toxin (BTC-A). This toxin is used for the treatment of spasticity of the muscles. It acts by blocking neuromuscular transmission. Furthermore, the mediatory of sensory inflammation is not allowed to be released by the toxin. It also blocks the peripheral neurotransmitters. In the central nervous system, sodium channels are inactivated by the toxin.[11]

For all neuropathic pains including PHN, it has been observed that BTX-A is very effective. Meta-analyses also found its effectiveness.[12]

With this background, the present study was carried out to study the effect of botulinum toxin on pain severity and quality of life in patients with PHN.


  Methods Top


This was a hospital record-based retrospective cohort study carried out over a period of 2 years from January 2019 to January 2021. Our study included 30 PHN patients who were treated with hypodermic injection of botulinum toxin (BTX-A).

Inclusion criteria

  1. Adult patients with PHN of either gender
  2. Having PHN for more than 3 months.


Exclusion criteria

  1. Age <18 years of either gender
  2. Having other comorbidities
  3. Not willing to give consent for the present study.


Institutional ethics committee permission was not taken as this is a hospital record-based study and the patient identifying information is not used in the present study. All the study participants were treated for PHN as per standard guidelines.

Patients did not respond well to drugs such as gabapentin, pregabalin, amitriptyline, duloxetine, selective serotonin reuptake inhibitors, opioids, nonsteroidal anti-inflammatory drugs, and few antidepressants. All patients were followed up for 6 months for the assessment of pain severity of the PHN. There were 14 males and 16 females aged from 44 to 81 years. The course of the disease was 3–9 months.

All patients were subjected to routine blood analysis and routine urine analysis, liver and kidney function electrocardiography, and electroencephalography tests before the treatment as per the standard guidelines and taking all aseptic precautions while collecting the blood sample.

Treatment methods and follow-up

Botox-A was injected subcutaneously, covering the involved area in a grid-like pattern. Dose per injection site varied from 2.5 to 5 units with 1–5 cm distance allowed among injection sites. The dosage was maximum of 100 units only once for each patient.

Before the injection, we measured Visual Analog Score (VAS) and the Quality of Life Scale (SF-36) score in all patients. PHN severity degree, frequency of attacks, and the use of all painkillers were also recorded. Each vial of BTX-A contained 100 U and was preserved at 2–8°C. It was diluted in saline before injection. Five units of BTX-A was injected subcutaneously. Two weeks after the injection, the abovementioned indexes were measured again. Measurements were repeated every month for 6 months through outpatient services.

Pain severity

VAS was used to measure pain severity. 0 represented no pain and 10 represented excruciating pain. One to three indicated mild pain, 4–6 showed moderate pain, 7–9 indicated severe pain, and 10 most intense pain [Figure 1].
Figure 1: Pain assessment tool

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Evaluation criteria for curative effect

The onset situation, 3–6 months before treatment, was taken as a base level and the pain severity was studied. Scale for VAS and SF-36 indexes was as follows:

  1. Markedly effectively improvement by 50% and over
  2. Effective improvement of 25.1% to 49%
  3. Ineffective improvement below 25%.


Total effective rate = markedly effective rate + effective rate.

Statistical analysis

The data were entered into the Microsoft Excel worksheet; we used OpenEpi statistical software to calculate the Chi-square and t-test values. Analysis of variance was used for comparing mean values for more than two groups. P < 0.05 indicated a significant difference.


  Results Top


[Table 1] shows the distribution of study subjects as per age and sex. Majority of the study subjects were in the age group of 60–69 years (40%) followed by 50–59 years (30%). The proportion of males and females was not much different, i.e., 46.7% versus 53.3%, respectively. For males, the most affected age group was 44–49 and 60–69 years, whereas for females, it was 50–59 and 70 years and above.
Table 1: Distribution of study subjects as per age and sex

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[Table 2] and [Chart 1] show the effect of botulinum toxin injection on pain severity, quality of life, and pain frequency at the end of 6 months. The mean pain severity as measured by VAS reduced significantly from 8.9 before BTX-A injections to 5.8 at the end of 6 months of therapy. The quality of life improved significantly after the therapy in 6 months. The pain frequency decreased significantly from 22.33 at baseline to 18.56 at the end of 6 months.
Table 2: Effect of botulinum toxin injection on pain severity, quality of life, and pain frequency at the end of 6 months

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[Table 3] and [Figure 2] show the effect of botulinum toxin injection on number of analgesics used by the patients. The average number of pain killers (analgesics) used by the patients was very high at before treatment, i.e., 87.43, which reduced significantly to 7 at 2 weeks after BTX-A and then slowly increased to 7.66 at 4 weeks; increased to 8.23 at 12 weeks and became 10.4 at 24 weeks.
Figure 2: Effect of botulinum toxin injection on number of analgesics used by the patients

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Table 3: Effect of botulinum toxin injection on number of analgesics used by the patients

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  Discussion Top


In the present study, the majority of the study subjects were in the age group of 60–69 years (40%) followed by 50–59 years (30%). The proportion of males and females was not much different, i.e., 46.7% versus 53.3%, respectively. For males, the most affected age group was 44–49 and 60–69 years, whereas for females, it was 50–59 and 70 years and above. The mean pain severity as measured by VAS reduced significantly from 8.9 before BTX-A injections to 5.8 at the end of 6 months of therapy. The quality of life improved significantly after the therapy in 6 months. The pain frequency decreased significantly from 22.33 at baseline to 18.56 at the end of 6 months. The average number of pain killers (analgesics) used by the patients was very high at before treatment, i.e., 87.43, which reduced significantly to 7 at 2 weeks after BTX-A and then slowly increased to 7.66 at 4 weeks, increased to 8.23 at 12 weeks, and became 10.4 at 24 weeks.

Ding et al.[13] reported that after treatment with the BTX-A, there was a significant reduction in the frequency of the pain attacks, duration of the pain attack as well as the severity of the pain. We also observed a significant reduction in the pain frequency. They also noted that the number of pain killer medication use reduced significantly which is also in accordance with the findings of the present study.

Li et al.[14] in their systematic review and meta-analysis of BTX-A versus lidocaine for PHN included seven randomized controlled trials having a total of 752 patients. They found that at 1 month, 2 months, and 3 months, the pain score as measured by VAS reduced significantly with a mean difference of − 2.31, −2.18, and − 1.93, respectively. We also found a significant reduction over a period of 6 months in the pain score. However, we did not use any comparison group. They also found that the adverse events were comparable in two groups. They concluded that BTX-A is safe and effective.

Ri et al.[15] searched literature pertaining to the safety and effectiveness of BTX-A for PHN. They included ten clinical trials and six case reports having 251 cases of PHN. They found that there was a significant reduction up to 30%–50% in the pain, and at the same time, significant improvement was seen in the quality of life. These findings are similar to the findings of the present study. They also noted that the adverse events were also absent even among the pregnant women. In the case reports they studied, observed that the patients were given the BTX-A for 2 years without any side effects. Like us, they also concluded that BTX-A is a safe and effective option in the treatment of PHN.

Egeo et al.[16] in their review of published studies on the utility of BTX-A for the control of neuropathic pain observed that most of the studies were reporting positive results for pain control even when there was no uniformity across the studies regarding the dose, technique of the injection, site of the injection, and dilution. We also report a positive effect of BTX-A on the pain scores in PHN patients.

Park and Park[17] also did a review of published studies for the effect of BTX-A for the control of all categories of neuropathic pain. From PubMed database of 1988–2017, they observed that BTX-A is effective in the treatment of PHN and other types of neuropathic pain. We also report similar findings from the present study.

Xiao et al.[18] in their randomized controlled trial, randomized 60 cases of PHN into three groups – BTX-A, lidocaine, and placebo. All three groups exhibited a significant reduction in pain on day 7 and at 3 months compared to baseline. However, the reduction in the BTX-A group was more compared to other two groups. All three groups also showed an improvement in the sleep time compared to baseline but, again the improvement was more marked in the BTX-A group. At the end of 3 months, it was observed that only 21.6% of the cases in the BTX-A group were using opioids compared to 52.6% in the lidocaine group and 66.7% in the placebo group. The authors concluded that BTX-A is a better, safer, and more effective option compared to lidocaine in the treatment of PHN.


  Conclusion Top


Using BTX-A for treating PNH gave promising and long-lasting results with very few adverse reactions. It can be considered a valid approach in the treatment of PNH, especially in nonresponsive patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Forbes HJ, Thomas SL, Smeeth L, Clayton T, Farmer R, Bhaskaran K, et al. A systematic review and meta-analysis of risk factors for postherpetic neuralgia. Pain 2016;157:30-54.  Back to cited text no. 1
    
2.
Kawai K, Gebremeskel BG, Acosta CJ. Systematic review of incidence and complications of herpes zoster: Towards a global perspective. BMJ Open 2014;4:e004833.  Back to cited text no. 2
    
3.
Chen LK, Arai H, Chen LY, Chou MY, Djauzi S, Dong B, et al. Looking back to move forward: A twenty-year audit of herpes zoster in Asia-Pacific. BMC Infect Dis 2017;17:213.  Back to cited text no. 3
    
4.
Gan EY, Tian EA, Tey HL. Management of herpes zoster and post-herpetic neuralgia. Am J Clin Dermatol 2013;14:77-85.  Back to cited text no. 4
    
5.
Massengill JS, Kittredge JL. Practical considerations in the pharmacological treatment of postherpetic neuralgia for the primary care provider. J Pain Res 2014;7:125-32.  Back to cited text no. 5
    
6.
Werner RN, Nikkels AF, Marinović B, Schäfer M, Czarnecka-Operacz M, Agius AM, et al. European consensus-based (S2k) Guideline on the Management of Herpes Zoster – Guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV), Part 1: Diagnosis. J Eur Acad Dermatol Venereol 2017;31:9-19.  Back to cited text no. 6
    
7.
Jeon YH. Herpes zoster and postherpetic neuralgia: Practical consideration for prevention and treatment. Korean J Pain 2015;28:177-84.  Back to cited text no. 7
    
8.
Dosenovic S, Jelicic Kadic A, Miljanovic M, Biocic M, Boric K, Cavar M, et al. Interventions for neuropathic pain: An overview of systematic reviews. Anesth Analg 2017;125:643-52.  Back to cited text no. 8
    
9.
Durham PL, Cady R. Insights into the mechanism of onabotulinumtoxinA in chronic migraine. Headache 2011;51:1573-7.  Back to cited text no. 9
    
10.
Lucioni A, Bales GT, Lotan TL, McGehee DS, Cook SP, Rapp DE. Botulinum toxin type A inhibits sensory neuropeptide release in rat bladder models of acute injury and chronic inflammation. BJU Int 2008;101:366-70.  Back to cited text no. 10
    
11.
Dolly JO, O'Connell MA. Neurotherapeutics to inhibit exocytosis from sensory neurons for the control of chronic pain. Curr Opin Pharmacol 2012;12:100-8.  Back to cited text no. 11
    
12.
Meng F, Peng K, Yang JP, Ji FH, Xia F, Meng XW. Botulinum toxin-A for the treatment of neuralgia: A systematic review and meta-analysis. J Pain Res 2018c;11:2343-51.  Back to cited text no. 12
    
13.
Ding XD, Zhong J, Liu YP, Chen HX. Botulinum as a toxin for treating post-herpetic neuralgia. Iran J Public Health 2017;46:608-11.  Back to cited text no. 13
    
14.
Li XL, Zeng X, Zeng S, He HP, Zeng Z, Peng LL, et al. Botulinum toxin A treatment for post-herpetic neuralgia: A systematic review and meta-analysis. Exp Ther Med 2020;19:1058-64.  Back to cited text no. 14
    
15.
Ri S, Kivi A, Wissel J. The safety and effect of local botulinumtoxin A injections for long-term management of chronic pain in post-herpetic neuralgia: Literature review and cases report treated with incobotulinumtoxin-A. J Pers Med 2021;11:758.  Back to cited text no. 15
    
16.
Egeo G, Fofi L, Barbanti P. Botulinum neurotoxin for the treatment of neuropathic pain. Front Neurol 2020;11:716.  Back to cited text no. 16
    
17.
Park J, Park HJ. Botulinum toxin for the treatment of neuropathic pain. Toxins (Basel) 2017;9:260.  Back to cited text no. 17
    
18.
Xiao L, Mackey S, Hui H, Xong D, Zhang Q, Zhang D. Subcutaneous injection of botulinum toxin a is beneficial in postherpetic neuralgia. Pain Med 2010;11:1827-33.  Back to cited text no. 18
    

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Correspondence Address:
R Prasuna,
Department of Dermatology, Venereology and Leprosy, Shadan Institute of Medical Sciences, Peeramcheru - 500 086, Telangana
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ajim.ajim_44_22



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