Neuropathic Pain due to Small Fiber Neuropathy in

Authors: Brigitte A Brouwer Bianca T A de Greef Janneke G J Hoeijmakers Margot Geerts Maarten van Kleef Ingemar S J Merkies Catharina G Faber

Publish Date: 2015/08/04

Volume: 32, Issue: 8, Pages: 611-621

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Abstract

Over the last 10 years the diagnosis small fiber neuropathy SFN has gained recognition worldwide Patients often suffer from severe neuropathic pain that may be difficult to treat A substantial subset of patients with SFN is aged 65 years or older and these patients often exhibit comorbidities and usage of multiple drugs making neuropathic pain treatment more challenging In this review we highlight relevant pathophysiological aspects and discuss currently used therapeutic strategies for neuropathic pain Possible pitfalls in neuropathic pain treatment in the elderly will be underlinedSmall fiber neuropathy SFN is a peripheral neuropathy in which predominantly the unmyelinated Cfibers and thinly myelinated Aδfibers are affected 1 The diagnosis is based on clinical symptoms reduced intraepidermal nerve fiber density in skin biopsy and/or abnormal temperature threshold tests 2 3 4 and no large nerve fiber involvement at physical examination or nerve conduction tests The prevalence is at least 53 cases per 100000 inhabitants and the rates are higher in elderly patients 5 Many conditions have been associated with SFN such as diabetes mellitus hyperlipidemia amyloidosis Fabry syndrome celiac disease sarcoidosis and other systemic illnesses human immunodeficiency virus HIV infection and hereditary sensory and autonomic neuropathies 3 Recently also pathogenic mutations in sodium channels NaV17 NaV18 and NaV19 were reported in patients with painful neuropathy 6 Despite a comprehensive workup of patients with SFN in a substantial proportion ranging from 24 to 93  in different series no underlying cause can be identified 3SFN patients often suffer from devastating pain and have a severely reduced quality of life 7 In addition to the typical SFNrelated complaints neuropathic pain and autonomic symptoms such as dry mouth dry eyes micturation problems or bowel dysfunction anxiety depression sleeping problems and fatigue may also influence qualityoflife expectations 8 9 10 Pain severity is associated with a high use of medication frequent physician consultations and substantial health care costs 10For the symptomatic treatment of neuropathic pain in SFN mostly general guidelines are used 11 12 13 14 15 Pharmacological treatment options mainly are antidepressants 16 anticonvulsants 17 and opioids 18 with generally disappointing results 14Understanding pathways and mechanisms involved in the development of neuropathic pain is important to define possible therapeutic targets Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage 19 As the definition suggests pain is a subjective phenomenon and is difficult to catch in an objective outcome measure 20 21 22 23 In humans pain represents a final integrative package consisting of neurophysiological processes as well as contextual psychological and sociocultural factors

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