University of Southern Denmark

Treatment of chronic post-herpetic neuralgia with autologous fat grafts

a first-in-the-world case reportSollie, Martin; Sørensen, Jens Ahm

Published in:British Journal of Pain

DOI:10.1177/2049463718817570

Publication date:2019

Document version:Accepted manuscript

Citation for pulished version (APA):Sollie, M., & Sørensen, J. A. (2019). Treatment of chronic post-herpetic neuralgia with autologous fat grafts: afirst-in-the-world case report. British Journal of Pain, 13(4), 239-243. https://doi.org/10.1177/2049463718817570

Go to publication entry in University of Southern Denmark's Research Portal

Terms of useThis work is brought to you by the University of Southern Denmark.Unless otherwise specified it has been shared according to the terms for self-archiving.If no other license is stated, these terms apply:

• You may download this work for personal use only. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying this open access versionIf you believe that this document breaches copyright please contact us providing details and we will investigate your claim.Please direct all enquiries to puresupport@bib.sdu.dk

Download date: 03. Jul. 2021

https://doi.org/10.1177/2049463718817570https://doi.org/10.1177/2049463718817570https://portal.findresearcher.sdu.dk/en/publications/695c6119-c8c9-4fab-8ad3-98d6ef8d9f21

1

Title

Treatment of Chronic Post-Herpetic Neuralgia with Autologous Fat Grafts: A first in the world case report

Abstract A 60-year-old woman suffering from severe chronic post-herpetic neuralgia (PHN) was treated with simple autologous fat grafting to the affected area of skin. Post-operatively she reported a great improvement in her symptoms. The effect was stable throughout the three months follow-up period. This case report presents a first in the world case of using fat grafting to treat chronic post-herpetic neuralgia and discusses the future potential of this as a primary treatment of this syndrome. This report presents partial data of a pilot study registered at clinicaltrials.org. (ClinicalTrials.gov Identifier: NCT03584061) Key points:

- PHN is chronic pain in the skin area of previous outbreak of Herpes Zoster. - PHN is a common, very painful and exceptionally drug-resistant condition. - The future prevalence of PHN will most likely increase as the population ages. - Pharmacological treatment is often unsuccessful and alternative treatments are not

available. - Autologous fat grafting shows promise in relieving pain from PHN.

Keywords Post-herpetic neuralgia, neuralgia, fat grafting, autologous fat grafting, stem cells.

2

Introduction Postherpetic neuralgia (PHN) is a neuropathic pain syndrome occurring after an outbreak herpes zoster (HZ) or “shingles”. It is caused by a reactivation of varicella zoster virus (VZV)1,2. The risk of developing PHN after HZ is reported being between 5% to 30% and the pain can last up to 10 years3. Clinically, the disease is characterized by a painful, unilateral vesicular eruption, which usually occurs with limited dermatomal distribution1. Pain is the predominant symptom in all phases of the disease and is reported in up to 90% of patients4. Most patients with PHN describe three types of pain: a constant deep, aching or burning pain, a paroxysmal, lancinating pain, and allodynia5.

Treatment of PHN is complex and the neuropathic pain is exceptionally drug-resistant5. Several broad recommendations on treatment of the neuropathic pain have been published 6–8. There is, however, currently, no internationally accepted guideline of treating PHN1. Treatment consists of topically and systemically administered medication. The present standard of care in not very effective and new treatments are needed. One such approach is autologous fat grafting. Fat tissue is abundant in most individuals and fat grafting is a safe and simple procedure. Fat grafting has shown potential in treating several painful conditions, such as post-mastectomy pain and scar-related pain, but it has not previously been used to treat post-herpetic neuralgia9–11.

Case presentation The patient was a 60-year old woman with pain in the areas of the previous shingles-rash. The reactivation of VZV had occurred three years previously. The area of outbreak measured 30 x 10 cm and stretched from the right side of the abdomen backwards towards the columna. The patient described the pain in the affected areas as a constant burning, throbbing pain. She had previously tried several pain medications for her condition without any effect. The medications tried were paracetamol, ibuprofen, tramadol, and gabapentin. As she felt they had no effect, she had stopped taking them prior to beginning our treatment. The affected area was marked pre-operatively by the surgeon and the patient. The marked area can be seen in photo 1. The patient was thoroughly informed of the potential risks of the procedure and signed a written consent form prior to surgery. [insert PHOTO1]

3

Photo 1. The area of pain marked pre-operatively. The area

marked with cross-markings was the area with the most predominant pain. This was the area where fat-injection

was performed.

Treatment The procedure was performed under general anesthesia. Liposuction (body-jet; Human med AG, Schwerin, Germany, http://www.humanmed.com) was performed by harvesting fat from the abdomen. Prior to harvesting, the area was prepared by installing ringer-adrenalin solution. 300 cc of fat was harvested. The fat was then decanted. After 15 minutes 120 cc of fat was injected sub-dermally in the marked area of pain using 10 ml cannulas. The patient was then fitted with a compression belt for the area of liposuction. The patient was discharged the same afternoon.

Investigations Outcomes measured were degree and quality of neuropathic pain and Quality of Life. Neuropathic pain was measured using the questionnaire: Neuropathic Pain Symptom Inventory Scale (NPSI) 12. Quality of Life was measured using the Short Form 36 (SF-36)

4

questionnaire 13–15. All questionnaires have validated translations into Danish12,15. The questionnaire was filled out by the patient pre-operatively and three months postoperatively.

Effect of treatment A few days after the surgery the patient reported improvement of her symptoms. This continued throughout the follow-up period. The patient experienced improvement in all measured parameters. Quality of life was measured using the SF-36 questionnaire. The patient reported improvement in all Quality of Life-parameters (FIGURE 1). The degree and quality of pain were measured using the NPSI. The patient reported improvement in all types of recorded pain (FIGURE 2). The patient did not report any disturbances in the sensation of the skin. There was no cosmetic effect of the treatment and no severe side effects were observed.

Figure 1. Results of the SF-36 recorded pre-surgery and 3 months post-surgery. The maximum score of each parameter was 100.

5

Figure 2. Results of the NPSI recorded pre-surgery and 3 months post-surgery. The maximum score of each parameter was 10.

Discussion Relevance of treatment: One in four people will suffer from HZ in their lifetime and the risk is markedly increased after the age of 50, with an incidence of almost 50% in elderly individuals. The prevalence of PHN will likely increase in the future as the population ages. The resolve of the disease is slow and the disease has been shown to have a negative impact on Quality of Life 16–18. Today’s treatment regimen of medications has potentially serious side effects and the risk of addiction. It is therefore important that we find an effective way of treating these patients. Pathophysiology: The pathophysiology behind HZ and PHN is neural damage to both the peripheral and central nervous system. HZ also induces neuroinflammation, a process that normally promotes regeneration and healing. If the resolution of neuroinflammation is disturbed, the result may

6

be chronic pain19,20. The direct damage and continued inflammation lower the threshold for action potentials, causing the nerves to fire painful signals, even by non-painful stimuli21. Skin biopsies of people affected by HZ and PHN have shown a lowered number of free epidermal nerve endings, with an even lower number in people with PHN compared to HZ alone 22. The aim of treatment should, therefore, be to modulate the signaling by the nerve endings by resolving the neuroinflammation and by repairing the damage and possibly help increase the number of free epidermal nerve ending. Fat grafting, safety, and possible effect: Fat grafting has been used for many years and has proven to be a simple and safe procedure. The most common side effects such as; numbness, bruising, pain, swelling, infection, and changes in skin sensation are usually mild and easily treated. Fat grafting has shown potential in treating painful conditions such as post-mastectomy pain syndrome, painful neurinomas, and painful scars9–11,23 The exact mechanism of fat grafting on painful conditions is not known and there are several theories being debated. First, fat grafting has a potential anti-inflammatory effect. In mouse model studies fat grafting to the sub-dermal tissues has shown an anti-inflammatory effect, both in the skin and in the spinal cord. The level of neuropathic pain was also reduced 24. The stem cells within the fatty tissue could also play a role in the pain-relieving effect. Adipose Derived Stem Cells (ADSC) have shown the ability to secrete several different growth factors in vitro, possibly inducing repair of damaged nerves25. The use of ADSC alone has also proven to have a pain relieving effect in people affected by neuropathic trigeminal pain26. The third possible effect could be the injected fats ability to act as a filler that cushions and improves chronic pain. In our study, this is unlikely as the amount of injected fat was very small. Fat grafting is also a relatively inexpensive treatment. When the liposuction equipment has been acquired, the cost of each individual treatment is low. Though no cost-benefit analysis has been performed, we would argue that a single treatment of fat grafting is preferable compared to a lifetime of medications. We believe that the method presented could be a potential treatment for patients affected by PHN. Future studies are needed to investigate the effect. This case study is a part of a pilot study currently undergoing at our department. Based on the promising preclinical and clinical results, we are planning a phase II study in our department to further test the feasibility and safety of this procedure (ClinicalTrials.gov Identifier: NCT03584061) )

References 1. Gan EY, Tian EAL, Tey HL. Management of herpes zoster and post-herpetic neuralgia. Am J Clin Dermatol 2013; 14: 77–85.

7

2. Schutzer-Weissmann J, Farquhar-Smith P. Post-herpetic neuralgia - a review of current management and future directions. Expert Opin Pharmacother 2017; 18: 1739–1750. 3. Kawai K, Gebremeskel BG, Acosta CJ. Systematic review of incidence and complications of herpes zoster: towards a global perspective. BMJ Open 2014; 4: e004833. 4. Johnson RW, Bouhassira D, Kassianos G, et al. The impact of herpes zoster and post-herpetic neuralgia on quality-of-life. BMC Med 2010; 8: 37. 5. Truini A, Galeotti F, Haanpaa M, et al. Pathophysiology of pain in postherpetic neuralgia: a clinical and neurophysiological study. Pain 2008; 140: 405–410. 6. Attal N, Cruccu G, Baron R, et al. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol 2010; 17: 1113-e88. 7. Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: systematic review, meta-analysis and updated NeuPSIG recommendations. Lancet Neurol 2015; 14: 162–173. 8. Moulin D, Boulanger A, Clark AJ, et al. Pharmacological management of chronic neuropathic pain: revised consensus statement from the Canadian Pain Society. Pain Res Manag 2014; 19: 328–335. 9. Caviggioli F, Maione L, Forcellini D, et al. Autologous fat graft in postmastectomy pain syndrome. Plast Reconstr Surg 2011; 128: 349–352. 10. Klinger M, Caviggioli F, Klinger FM, et al. Autologous fat graft in scar treatment. J Craniofac Surg 2013; 24: 1610–1615. 11. Maione L, Vinci V, Caviggioli F, et al. Autologous fat graft in postmastectomy pain syndrome following breast conservative surgery and radiotherapy. Aesthetic Plast Surg 2014; 38: 528–532. 12. Bouhassira D, Attal N, Fermanian J, et al. Development and validation of the Neuropathic Pain Symptom Inventory. Pain 2004; 108: 248–257. 13. Bjorner JB, Damsgaard MT, Watt T, et al. Tests of data quality, scaling assumptions, and reliability of the Danish SF-36. J Clin Epidemiol 1998; 51: 1001–1011. 14. Bjorner JB, Kreiner S, Ware JE, et al. Differential item functioning in the Danish translation of the SF-36. J Clin Epidemiol 1998; 51: 1189–1202. 15. Bjorner JB, Thunedborg K, Kristensen TS, et al. The Danish SF-36 Health Survey: translation and preliminary validity studies. J Clin Epidemiol 1998; 51: 991–999. 16. Laurent B, Vicaut E, Leplège A, et al. Prevalence and impact on quality of life of post-herpetic neuralgia in French medical centers specialized in chronic pain management: the ZOCAD study. Med Mal Infect 2014; 44: 515–524. 17. Mizukami A, Sato K, Adachi K, et al. Impact of Herpes Zoster and Post-Herpetic Neuralgia on Health-Related Quality of Life in Japanese Adults Aged 60 Years or Older: Results from a Prospective, Observational Cohort Study. Clin Drug Investig 2018; 38: 29–37. 18. Serpell M, Gater A, Carroll S, et al. Burden of post-herpetic neuralgia in a sample of UK residents aged 50 years or older: findings from the Zoster Quality of Life (ZQOL) study. Health Qual Life Outcomes 2014; 12: 92. 19. Sommer C, Leinders M, Üçeyler N. Inflammation in the pathophysiology of neuropathic pain. Pain 2018; 159: 595–602. 20. Huh Y, Ji R-R, Chen G. Neuroinflammation, Bone Marrow Stem Cells, and Chronic Pain. Front Immunol 2017; 8: 1014. 21. Woolf CJ, Mannion RJ. Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet 1999; 353: 1959–1964. 22. Oaklander AL. The density of remaining nerve endings in human skin with and without

8

postherpetic neuralgia after shingles. Pain 2001; 92: 139–145. 23. Vaienti L, Gazzola R, Villani F, et al. Perineural fat grafting in the treatment of painful neuromas. Tech Hand Up Extrem Surg 2012; 16: 52–55. 24. Huang S-H, Wu S-H, Lee S-S, et al. Fat Grafting in Burn Scar Alleviates Neuropathic Pain via Anti-Inflammation Effect in Scar and Spinal Cord. PLoS One; 10. Epub ahead of print September 14, 2015. DOI: 10.1371/journal.pone.0137563. 25. Rehman J, Traktuev D, Li J, et al. Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation 2004; 109: 1292–1298. 26. Vickers ER, Karsten E, Flood J, et al. A preliminary report on stem cell therapy for neuropathic pain in humans. J Pain Res 2014; 7: 255–263.