Botulinum Toxin Treatment in Post Herpetic Neuralgia a Review

Introduction

Herpes zoster results from reactivation of childhood chicken pox virus during adulthood. Eruption of small vesicles over the skin with typical distribution along the course of the nerve routes or peripheral nerves is the characteristic symptom of the disease. The lesions can involve the face, trunk or limbs or affect more than one region. When on the trunk, large parts of the body may be involved. Skin lesions are often accompanied by intense itch. After a few weeks, the vesicles dry up and leave scars and areas of e skin discoloration. Some patients with herpes may develop pain (post-herpetic neuralgia) during or shortly after healing of skin lesions, but majority of the patients experience the pain weeks or months later. The pain of herpes zoster is one of the most severe pains known to mankind. It is often described as sharp and jabbing , felt in the distribution of the involved nerves. The percentage of patients who develop pain after shingles, is highly dependent on the age at the onset of their symptoms; 5% among individuals younger than 60 and 20% among patients who are 80 years of age or older [1]. In adults, vaccination against shingles reduces the incidence of post-herpetic neuralgia. In many patients, pain lasts for months or even years, incapacitating the affected patient.

Treatment

Argoff, [2] based on the guidelines of American Academy of Neurology and European Federation of Neurological Societies describes tricyclic antidepressants, gabapentin, pregabalin, and the topical lidocaine 5% patch as first line of treatment in PHN. Opioids, tramadol, capsaicin cream, and the capsaicin 8% patch are recommended as either second- or third-line therapies. Serotonin-norepinephrine reuptake inhibitors, the anticonvulsants carbamazepine and valproic acid are also partially effective. In refractory patient’s short course of oral steroids, invasive procedures such as sympathetic blockade, intrathecal steroids, and implantable spinal cord stimulators have been studied and have been helpful in some patients.

Botulinum Toxin Treatment

Animal studies of the past [2-3] decades have clearly shown that injection of the botulinum toxins A and B into the skin blocks local accumulation of pain neurotransmitters and pain modulators such as glutamate and calcitonin gene related peptides. More recent studies have strongly suggest that the analgesic effects of local BoNT injection in the animal models of pain has an additional central mechanism. Botulinum toxins B and A have been traced to the spinal cord sensory neurons after peripheral injections in to the muscles [3,4]. The positive results of PREEMPT studies led to approval of on a botulinum toxin A (Botox) for chronic migraine in Europe and US in 2010. Since then a large number of clinical trials strongly suggests efficacy of Botulinum toxins in a variety of pain disorders [5].

Method of the Review

The published literature on the use of botulinum toxins in postherpetic neuralgia was reviewed, using Medline and Ovis SP search engines. The search included all English manuscripts published between January 1st, 1989 (the year that botulinum toxin was introduced into the market) to February 1st, 20019. The search words included botulinum toxin, Botulinum neurotoxin , Herpes Zoster and Post-herpetic Neuralgia.

Results

A total of 37 manuscripts were identified. Of these, 10 studies specifically studied the effect of botulinum toxins on post herpetic neuralgia (Table 1). Two studies, represented high quality, randomized, blinded, placebo controlled clinical trials [6,7].

  

    
Authors    and date 
    
Type    of study
    
Number    of patients 
    
Toxin    and dose in Units (U), mode of injection
    
Result
  
  

    
Ding    XD et al 2019 
    
Open    label Prospective
    
59
    
Prosigne    50-100 U SC
    
Marked    pain reduction in 46.5% of patients
  
  

    
Jain    et al 2017
    
Case    series
    
2
    
Dysport,    500 U, SC
    
Pain    in VAS dropped to 2 and 3 after two weeks
  
  

    
Moon    et al 2016
    
Single    case
    
1
    
Botox,    50 units, into lumbar plexus
    
Pain    measures at baseline as 8-10 in VAS deopped to 2-3 after injection 
  
  

    
Apalla    et al 2013 6
    
Double    blind, placebo controlled
    
30
    
Botox,    100U SC
    
At    least 50% reduction of VAS score in 13 pts in toxin group (P< 0.001)
  
  

    
Li    & Xio 2015
    
Single    case
    
1
    
Bobtulinum    toxin -A? 100 units SC
    
Reduction    of VAS from 8-9 to 2-3 Ophthalmic PHN
  
  

    
Emad    et al 2012 
    
Cas    series
    
15
    
Botox    15U every 2 cm, SC
    
Baseline    VAS 6.4 – at week 4: 3.7 (P<0.03)
  
  

    
Xiao    et al 2010 7
    
Double    blind, placebo controlled
    
60,    20 per arm-Toxin, placebo, Lidocaine
    
Prosigne    Varied- less than 200 U SC
    
VAS    score diminished in all three arms but more in Toxin arm. 
  
  

    
Sotrion    et al 2009 10
    
Case    series
    
3
    
Botox,100    U SC
    
Pain    dropped from 8-10 in VAS to 1-3 between post-injection weeks 2-8
  
  

    
Liu    et al 2006
    
Single    case
    
1
    
Botox,    100U SC
    
Pain    severity reduced to 1 from 10 in VAS. 
  
  

    
Turk    et al 2005
    
Case    series 
    
8
    
Botox    100 U SC
    
Reduced    pain
  
  

    
VAS: Visual    Analogue Scale; SC: Subcutaneous 
  

Table 1: Published manuscripts on the subject of BoNT treatment in post-herpetic neuralgia.