Postherpetic Neuralgia (PHN) is a syndrome defined by chronic neuropathic pain that persists for more than 3 months after the resolution of a Herpes Zoster (HZ) episode [1].

PHN is characterized by persistent and debilitating pain with a dermatomal distribution, lasting from months to years, affecting nerve fibers and the skin with a constant sensation of burning and stabbing. It is typically refractory to treatment, negatively impacting the patient's quality of life [2,3].

It is still not known why some patients develop PHN, whereas the majority does not, although some risk factors for PHN have been identified in previous studies: older age, immunosuppression, high acute pain during acute zoster and large extent of rash [1].

Upon reactivation, the virus replicates in neuronal cell bodies, and virions shed from the cells which are carried down the nerve to the area of skin innervated by that ganglion. In the skin, the virus causes local inflammation and blistering. The pain caused by zoster is due to inflammation of affected nerves with the virus [4,5].

The first and second lines of treatment, according to the European Federation of Neurological Societies including tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, pregabalin, gabapentin, tramadol, capsaicin patches, and lidocaine patches. Nevertheless, patients who experience persistent pain despite conservative treatment may benefit greatly from interventional therapies [3].

Within the context of interventional therapies, we find epidural nerve block, pulsed radiofrequency, and the application of botulinum toxin type A (BTX-A). BTX-A has shown efficacy in pain treatment and has demonstrated improvement in the patient's quality of life, especially in cases refractory to previous therapies [3,6].

BTX?A is a neurotoxic protein produced by Clostridium botulinum and is used in the clinic to treat muscle spasticity through blockade of neuromuscular transmission. Furthermore, inhibits the release of sensory inflammatory mediators and peripheral neurotransmitters inactivating membrane sodium channels in central neurons [4].

It is widely used in various pathologies such as intractable neuropathic pain, diabetic neuropathy, trigeminal neuralgia, phantom limb pain, post-stroke pain, and in cosmetic medicine, particularly for excessive muscle stiffness, spasticity, and dystonia for over 40 years (7).

PHN remains underdiagnosed and inadequately treated. The use of BTX-A in the treatment of PHN has been explored as a promising therapeutic option. Clinical studies have investigated its efficacy, and the results have been encouraging, with reports of significant pain reduction, decrease in the frequency and intensity of pain episodes, as well as improvement in patients' quality of life, with minimal side effects [7,8,9].

In this study, we report on 7 patients diagnosed with PHN who were treated with incobotulinumtoxin A (incoBoNT/A) at a private dermatology clinic in São Paulo, evaluating its impact on pain improvement and the patient's quality of life.

This is a retrospective observational study in which information was obtained from the medical records of 7 patients diagnosed with PHN who underwent treatment with BTX-A at a private dermatology clinic in São Paulo.

Questionnaires were administered using two scales: the Visual/Numeric pain Scale (VNS) to analyze the patient's pain score before the initiation of treatment and at 2, 6, 12, and 16 weeks, and the assessment of anxiety and depression levels using the Hospital Anxiety and Depression (HAD) scale, evaluated before treatment and 8 weeks after.

IncoBoNT/A (Xeomin®) was diluted with 4 ml of saline solution and injected subcutaneously in a serial way, with a distance of 1 cm between each application point, within a radius of 1 to 2 centimeters around the painful region. Two units were administered per point, with a minimum dose of 78 units in patients with an initial VNS score of 6 and a maximum dose of 180 units in patients with an initial score of 9.

The Visual/Numeric pain Scale (VNS) was assessed before the initiation of the proposed therapy and at 2, 6, 12, and 16 weeks after treatment, as shown in Table 1. The VNS demonstrated that at the onset of symptoms, 71.4% of patients reported intense pain, while 28.6% reported moderate pain. At 6 weeks after the administration of botulinum toxin type A, 57.1% experienced mild pain and 42.9% were pain-free. After 12 weeks, 85.7% of patients no longer had pain, and at 16 weeks, 100% of patients were pain-free

Table 1: Dose of BTX-Aused in each patient and pain assessment VNSat the time of application and 2, 6, 12 and 16 weeks later.

The assessment of anxiety and depression levels (HAD) was administered to patients when they first arrived at the dermatology clinic with pain and without treatment, and again after 8 weeks. Initially, when patients experienced pain, it was noted that 71.4% showed possible anxiety and 14.3% showed possible depression. After 8 weeks, with the improvement in pain, all patients showed unlikely levels of anxiety and depression.

No serious adverse reactions and/or increased pain were observed during the treatment. No serious adverse reactions and/or increased pain were observed during the treatment.

The mechanism of action of IncoBoNT/A is the pre-synaptic blockade of acetylcholine release at the neuromuscular junction. By reducing the release of glutamate through the reduction of neuronal activity, it exerts an effect on neuropathic pain, contributing to the control or modulation of neurogenic inflammation [7,10]. It is important to emphasize that its effects are not systematically distributed but rather localized. Botulinum toxin has an analgesic effect independent of muscle relaxation, as evidenced by the difference in duration between muscle relaxation and pain relief [8].

One of the major benefits of using BTX-A is its relative safety, especially when compared to other more invasive treatment options or those with potential significant side effects. Additionally, it is a minimally invasive procedure that is generally well-tolerated by patients [4, 10].

In this context, numerous studies support our findings regarding the use of botulinum toxin in the treatment of postherpetic neuralgia, both in terms of pain reduction and improvement in the patient's quality of life. It proves to be a potent, effective, and safe therapeutic option [2, 11]. It has been demonstrated that early use of first and second-line medications combined with individual interventions, with pulsed radiofrequency and BTX-A being the most effective, can serve as primary therapy for postherpetic neuralgia, resulting in improved pain relief [10].

In Li et al., the efficacy of BTX-A was compared with lidocaine in the treatment of postherpetic neuralgia. BTX-A was found to be more effective, with lower pain scores observed up to 24 weeks after treatment. The dose ranged from 100-200 units, administered via intradermal and subcutaneous injections. There were no differences in adverse events between the substances [4].

Several studies have associated pain improvement with an increase in the patient's quality of life. Pain reduction was evaluated using the VNS, and this effect persisted for approximately 2 months or more [6, 7, 12].

The articles by Apalla et al. and Xiao et al. conducted a study with 30 patients with NPH who were randomized between BTX-A and placebo. Both studies achieved over 50% improvement in pain and quality of life. On the other hand, the study by Ranoux et al. used 29 patients who were randomized for treatment with BTX-A and placebo, resulting in over 50% improvement in pain for the patients who received BTX-A. When analyzing the results on the EVN scale and comparing them with the studies by Apalla et al., Xiao et al., and Ranoux et al., we observed similarities in the duration of pain improvement with IncoBoNT/A. The three articles, along with our analysis, provided evidence of pain reduction in the first two weeks and stable pain levels from 12 to 16 weeks. In some cases, a positive effect was also observed up to 24 weeks [8, 9, 13].

Just like in our study, other works have observed a direct proportional relationship between pain intensity and the levels of anxiety and depression in patients [1]. Therefore, once treated, patients benefit from positive effects in the psychological realm as well, reducing depressive and anxious symptoms, and consequently improving their quality of life.

Moreover, Xeomin® is a purified form of the neurotoxin without conjugated proteins in its composition, that way it becomes safer for repeating the dose within a shorter interval, which is essential for better treatment efficacy.

The treatment of PHN is challenging due to its refractory nature. The use of IncoBoNT/A (Xeomin®) in PHN represents a promising therapeutic approach capable of providing pain relief and enhancing patients' quality of life.

We conclude that subcutaneous injection of Xeomin® proves to be effective in the treatment of this disease, with a consequent improvement in the patient's quality of life. Large-scale studies and long-term follow-up are warranted to further confirm the analgesic effects of IncoBoNT/A for patients suffering from the pain of PHN.

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