Post-Herpetic Pain Managed According to The Recommendations of the Italian Society of Mesotherapy

Domenico Russo 1 , Massimo Mammucari 2* , Silvia Natoli 3 , Enrica Maggiori 2 , Luciano Antonaci 2 , Renato Fanelli 2 , Chiara Giorgio 4 , Anna Rosa Catizzone 5 , Fiammetta Troili 5 , Alessandra Gallo 5 , Costanza Guglielmo 5 , Flora Canzona 6 , Dario Dorato 5 , Raffaele Di Marzo 5 , Stefania Santini 5 , Rodolfo Gallo 5 , Piergiovanni Rocchi 5 , Gianpaolo Ronconi 7 , Paola E Ferrara 7 , Michela Guarda 1

or opiates, but adverse events may occur frequently [6][7][8]. Systemic drugs use is limited by the patient's age, illnesses, and coexisting treatment. Mesotherapy is a technique by which a small quantity of drug is administered in the superficial layer of the skin, through several micro-injections. The injected drug spreads slowly into the underlying tissues and generates analgesia, equivalent to systemic treatment [9,10]. Indeed, it has been hypothesized that intradermal administration allows the drug to interact with dermal structures capable of modulating some forms of pain [11]. This technique is useful in many localized painful conditions, particularly when systemic drugs are not tolerated, or the risk of drugdrug interactions is high [12]. We report a clinical case in order to underline the usefulness of the applied intradermal therapy according to the recommendations of the Italian mesotherapy society.

Case Report
A 68 years old female, affected by chronic renal insufficiency, aortic and mitral insufficiency, and rheumatoid arthritis, assumed prednisone and methotrexate. She developed Herpes Zoster disease, all along the right T5 dermatome. The Zoster was managed with Famciclovir (1500 mg/day for ten days). One month later, the skin eruption was resolving, but the ongoing pain persisted and about 20 severe painful attacks occurred every day.
When the patient arrives at our service, she reported past severe drowsiness using pregabalin, duloxetine, and Venlafaxine, so all these drugs had been discontinued. At the time she was assuming tapentadol 100 mg/day, reporting nausea and drowsiness, so we switched to fentanyl patch 12,5 mcg/h, started micronized palmitoylethanolamide (PEA) every 12 hours, and performed a Scrambler Therapy cycle. Scrambler Therapy is an electro-analgesia used on neuropathic pain [13,14]; it was applied 45-minutes daily, for ten consecutive days. After two weeks, ongoing pain became light, but we did not obtain any improvement in the number and intensity of painful attacks. The skin healed, so we started the Lidocaine patch (700 mg 12 hours, every day) and continued fentanyl and PEA. Two weeks later, daily painful attacks decreased to 10 and pain was getting better.
Unfortunately, severe nausea raised again and fentanyl was discontinued. Moreover, the Lidocaine  patch caused skin irritation, after three weeks of application. All drugs were discontinued, and pain rose immediately to the previous level. Itch became a dominant symptom. Pain levels and adverse events for every step are reported in Table-1.
Since the patient showed intolerance to anticonvulsants, antidepressants, opioids, and lidocaine patches, we decided to apply local intradermal therapy (Fig-1). This term refers to a series of dermal micro deposits of the drug, which results in its slow diffusion into the underlying tissues [11,12]. We implemented the first session of mesotherapy with lidocaine 10 mg/ml solution. Every session we injected about 25 mg of lidocaine, by a needle (27G, 4 mm) inclined 30° with respect to the skin surface. For each micro-puncture, a minimal amount of medication was injected (0,1-0,2 ml) to produce a small wheal, which raised slightly the surface layer of the skin. To provide a better comfort to the patients we did not inject in the painful area, but all along the superior and inferior border of the interested dermatome. Every point of injection was about 3 cm far from the previous. The patients reported moderate but bearable pain, during the needle insertion. After a week, the patient reported significant improvement, increasing in the following weeks. Only itch worse. After a week from the last session and after a month of follow up the number of pain attacks did not increase (Table-2).

Discussion
Despite the lack of data in this indication [15], the reported case suggests that post-herpetic neuralgia could be managed with mesotherapy. Our patient suspended all systemic drugs for adverse events. The lidocaine-based patch is a good option to reduce postherpetic pain; however, local adverse reactions may limit its application. In this critical condition, we decided to apply lidocaine by intradermal route (mesotherapy technique). A significant reduction in the number of painful attacks was recorded, with considerable patient satisfaction. Mesotherapy has produced better results in terms of efficacy and tolerability than the patch. This result was maintained one month after the last session. In contrast, when we suspended the lidocaine patch, the patient had an immediate exacerbation of pain. The greater diffusion in the tissues underlying the site of inoculation could in part explain this difference, but mesotherapy could act not only pharmacologically: the skin could play an active role as well the reflexological effect due to the needle insertion [16].
In favor of this hypothesis, data have recently been recorded in favor of intradermal treatment both with respect to the oral route [17] and to the intravenous route [18]. It would be interesting to compare lidocaine patch versus lidocaine mesotherapy in a randomized controlled trial.

Conclusion
Waiting for wider clinical studies, we recommend applying mesotherapy according to the rules of good clinical practice (Table-3) constantly updated by the Italian mesotherapy society [20]. We strongly recommend involving the patient in the therapeutic strategy through valid informed consent [21]. We strongly emphasize that patient satisfaction is a crucial element in pain therapy. Mesotherapy allows exploiting a further weapon useful in some forms of localized pain. The role played by local intradermal micro-injection (mesotherapy) should be better evaluated in clinical research. Even the health Authorities could suggest the application of this technique for its drug sparing effect.

Contribution
DR treated and described the case, MM and DR wrote the article, all the other authors reviewed and approved the case according with the Italian mesotherapy's recommendation before submitting it.

Funding
No external funding received to write this Case Report.