Abstract
Postherpetic neuralgia (PHN) is a common and exceptionally drug-resistant neuropathic pain condition. In this cross-sectional skin biopsy study, seeking information on the responsible pathophysiological mechanisms we assessed how ophthalmic PHN affects sensory and autonomic skin innervation. We took 2-mm supraorbital punch skin biopsies from the affected and unaffected sides in 10 patients with ophthalmic PHN. Using indirect immunofluorescence and a large panel of antibodies including protein gene product (PGP) 9.5 we quantified epidermal unmyelinated, dermal myelinated and autonomic nerve fibers. Although skin biopsy showed reduced epidermal and dermal myelinated fiber density in specimens from the affected side, the epidermal/dermal myelinated nerve fiber ratio was lower in the affected than in the unaffected side (p < 0.001), thus suggesting a predominant epidermal unmyelinated nerve fiber loss. Conversely, autonomic skin innervation was spared. Our study showing that ophthalmic PHN predominantly affects unmyelinated nerve fiber and spares autonomic nerve fiber might help to understand the pathophysiological mechanisms underlying this difficult-to-treat condition.
Highlights
Ophthalmic postherpetic neuralgia (PHN) is a disabling and extensively investigated neuropathic pain condition caused by herpes zoster and persisting or recurring for at least 3 months in areas supplied by the ophthalmic division of the trigeminal nerve (IHS Classification, 2013)
An approach based on immunofluorescence and confocal microscopy using double and triple immunostaining with an extensive panel of antibodies including the pan-neuronal marker protein gene product (PGP) 9.5, the basement membrane marker, collagen IV (ColIV), and antibodies for various myelinated and unmyelinated nerve fiber populations, has proved to provide distinct information on sensory and autonomic nerve fibers, and possibly assess skin innervation more accurately (Doppler et al, 2012; Nolano et al, 2013)
Confocal immunofluorescence analysis showed that skin innervation in the supraorbital punch skin biopsies from patients with PHN differed strikingly between the unaffected (Figures 2A,C,E) and affected sides (Figures 2B,D,F)
Summary
Studies assessing cutaneous innervation in skin biopsy specimens have provided new insight into the mechanisms underlying neuropathic pain in several conditions (Sommer and Lauria, 2007). Epidermal innervation consists mainly of unmyelinated C-fiber terminals, with relatively few small myelinated Aδ-fibers that lose their myelin sheath and reach the epidermis as unmyelinated free nerve endings. An approach based on immunofluorescence and confocal microscopy using double and triple immunostaining with an extensive panel of antibodies including the pan-neuronal marker PGP 9.5, the basement membrane marker, collagen IV (ColIV), and antibodies for various myelinated and unmyelinated nerve fiber populations, has proved to provide distinct information on sensory and autonomic nerve fibers, and possibly assess skin innervation more accurately (Doppler et al, 2012; Nolano et al, 2013)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.