TY - JOUR
T1 - Small-fiber neuropathy: Expanding the clinical pain universe
AU - Sopacua, M.
AU - Hoeijmakers, J.G.J.
AU - Merkies, I.S.J.
AU - Lauria, G.
AU - Waxman, S.G.
AU - Faber, C.G.
N1 - Funding Information:
Part of our research is funded by the European Union seventh Frame-
Funding Information:
work Programme (grant n 602273).
Funding Information:
information European Union seventh Framework Programme, Grant/Award Number: 602273Part of our research is funded by the European Union seventh Framework Programme (grant n 602273). All authors contributed equally to researching data for the article, discussion of content, writing the article, and to the editing and review of the manuscript before submission.
Publisher Copyright:
© 2018 Peripheral Nerve Society
PY - 2019/3/1
Y1 - 2019/3/1
N2 - Small-fiber neuropathy (SFN) is a disorder of thinly myelinated A delta and unmyelinated C fibers. SFN is clinically dominated by neuropathic pain and autonomic complaints, leading to a significant reduction in quality of life. According to international criteria, the diagnosis is established by the assessment of intraepidermal nerve fiber density and/or quantitative sensory testing. SFN is mainly associated with autoimmune diseases, sodium channel gene variants, diabetes mellitus, and vitamin B12 deficiencies, although in more than one half of patients no etiology can be identified. Recently, gain-of-function variants in the genes encoding for the Na(v)1.7, Na(v)1.8 and Na(v)1.9 sodium channel subunits have been discovered in SFN patients, enlarging the spectrum of underlying conditions. Sodium channel gene variants associated with SFN can lead to a diversity of phenotypes, including different pain distributions and presence or absence of autonomic symptoms. This suggests that SFN is part of a clinical continuum. New assessments might contribute to a better understanding of the cellular and molecular substrates of SFN and might provide improved diagnostic methods and trial designs in the future. Identification of the underlying mechanisms may inform the development of drugs that more effectively address neuropathic pain and autonomic symptoms of SFN.
AB - Small-fiber neuropathy (SFN) is a disorder of thinly myelinated A delta and unmyelinated C fibers. SFN is clinically dominated by neuropathic pain and autonomic complaints, leading to a significant reduction in quality of life. According to international criteria, the diagnosis is established by the assessment of intraepidermal nerve fiber density and/or quantitative sensory testing. SFN is mainly associated with autoimmune diseases, sodium channel gene variants, diabetes mellitus, and vitamin B12 deficiencies, although in more than one half of patients no etiology can be identified. Recently, gain-of-function variants in the genes encoding for the Na(v)1.7, Na(v)1.8 and Na(v)1.9 sodium channel subunits have been discovered in SFN patients, enlarging the spectrum of underlying conditions. Sodium channel gene variants associated with SFN can lead to a diversity of phenotypes, including different pain distributions and presence or absence of autonomic symptoms. This suggests that SFN is part of a clinical continuum. New assessments might contribute to a better understanding of the cellular and molecular substrates of SFN and might provide improved diagnostic methods and trial designs in the future. Identification of the underlying mechanisms may inform the development of drugs that more effectively address neuropathic pain and autonomic symptoms of SFN.
KW - amyotrophic-lateral-sclerosis
KW - autosomal-dominant
KW - congenital insensitivity
KW - corneal confocal microscopy
KW - diagnostic criteria
KW - inherited erythromelalgia
KW - laser-evoked potentials
KW - na(v)1.7 sodium-channels
KW - neuropathic pain
KW - of-function mutation
KW - pain management
KW - scn9a mutations
KW - skin biopsy
KW - small-fiber neuropathy
KW - sodium channel variants
KW - SKIN BIOPSY
KW - INHERITED ERYTHROMELALGIA
KW - OF-FUNCTION MUTATION
KW - NA(V)1.7 SODIUM-CHANNELS
KW - CONGENITAL INSENSITIVITY
KW - SCN9A MUTATIONS
KW - AMYOTROPHIC-LATERAL-SCLEROSIS
KW - LASER-EVOKED POTENTIALS
KW - CORNEAL CONFOCAL MICROSCOPY
KW - AUTOSOMAL-DOMINANT
U2 - 10.1111/jns.12298
DO - 10.1111/jns.12298
M3 - (Systematic) Review article
SN - 1085-9489
VL - 24
SP - 19
EP - 33
JO - Journal of the Peripheral Nervous System
JF - Journal of the Peripheral Nervous System
IS - 1
ER -