TY - JOUR
T1 - Intraepidermal Nerve Fiber Analysis in Human Patients and Animal Models of Peripheral Neuropathy
T2 - A Comparative Review
AU - Mangus, Lisa M.
AU - Rao, Deepa B.
AU - Ebenezer, Gigi J.
N1 - Funding Information:
The authors would like to thank Michael Polydefkis and Joseph Mankowski for their professional guidance as well as Baohan Pan, Kelly Wagner, and Megan McCarron for their expert technical assistance. The author(s) received no financial support for the research, authorship, and/or publication of this article.
Publisher Copyright:
© The Author(s) 2019.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Analysis of intraepidermal nerve fibers (IENFs) in skin biopsy samples has become a standard clinical tool for diagnosing peripheral neuropathies in human patients. Compared to sural nerve biopsy, skin biopsy is safer, less invasive, and can be performed repeatedly to facilitate longitudinal assessment. Intraepidermal nerve fiber analysis is also more sensitive than conventional nerve histology or electrophysiological tests for detecting damage to small-diameter sensory nerve fibers. The techniques used for IENF analysis in humans have been adapted for large and small animal models and successfully used in studies of diabetic neuropathy, chemotherapy-induced peripheral neuropathy, HIV-associated sensory neuropathy, among others. Although IENF analysis has yet to become a routine end point in nonclinical safety testing, it has the potential to serve as a highly relevant indicator of sensory nerve fiber status in neurotoxicity studies, as well as development of neuroprotective and neuroregenerative therapies. Recently, there is also interest in the evaluation of IENF via skin biopsy as a biomarker of small fiber neuropathy in the regulatory setting. This article provides an overview of the anatomic and pathophysiologic principles behind IENF analysis, its use as a diagnostic tool in humans, and applications in animal models with focus on comparative methodology and considerations for study design.
AB - Analysis of intraepidermal nerve fibers (IENFs) in skin biopsy samples has become a standard clinical tool for diagnosing peripheral neuropathies in human patients. Compared to sural nerve biopsy, skin biopsy is safer, less invasive, and can be performed repeatedly to facilitate longitudinal assessment. Intraepidermal nerve fiber analysis is also more sensitive than conventional nerve histology or electrophysiological tests for detecting damage to small-diameter sensory nerve fibers. The techniques used for IENF analysis in humans have been adapted for large and small animal models and successfully used in studies of diabetic neuropathy, chemotherapy-induced peripheral neuropathy, HIV-associated sensory neuropathy, among others. Although IENF analysis has yet to become a routine end point in nonclinical safety testing, it has the potential to serve as a highly relevant indicator of sensory nerve fiber status in neurotoxicity studies, as well as development of neuroprotective and neuroregenerative therapies. Recently, there is also interest in the evaluation of IENF via skin biopsy as a biomarker of small fiber neuropathy in the regulatory setting. This article provides an overview of the anatomic and pathophysiologic principles behind IENF analysis, its use as a diagnostic tool in humans, and applications in animal models with focus on comparative methodology and considerations for study design.
KW - intraepidermal nerve fibers (IENFs)
KW - peripheral nerve
KW - peripheral neuropathy
KW - primate
KW - rodent
KW - sensory neuropathy
KW - stereology
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U2 - 10.1177/0192623319855969
DO - 10.1177/0192623319855969
M3 - Article
C2 - 31221022
AN - SCOPUS:85068163950
SN - 0192-6233
VL - 48
SP - 59
EP - 70
JO - Toxicologic pathology
JF - Toxicologic pathology
IS - 1
ER -