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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. [ABSTRACT FROM AUTHOR]

The morphology of cutaneous sensory and autonomic innervation in human trigeminal territory is still unknown. The aim of this study is to describe facial cutaneous innervation using skin biopsy. This new tool could be useful in understanding the mechanisms underlying several facial pain conditions. In 30 healthy subjects, we quantified epidermal nerve fibers ( ENFs) and dermal myelinated fibers ( MFs) in V1, V2 and V3, using indirect immunofluorescence and confocal microscopy applied to 2-mm punch skin biopsies from areas adjacent to the eyebrow, upper and lower lip. Using selective markers, we also evaluated the distribution of peptidergic, cholinergic and noradrenergic fibers. Facial skin appeared abundantly innervated and rich in annexes. The ENF density decreased and the MF density increased, moving from the supraorbital to the perioral skin. Noradrenergic sudomotor fibers were particularly and constantly expressed compared with other body sites. Distribution of vasoactive intestinal peptide-immunoreactive ( VIP-ir) fibers appeared peculiar for their constant presence in the subepidermal neural plexus - in close contact, but without colocalization with calcitonin gene related peptide ( CGRP) and substance P ( Sub- P)-ir fibers. Finally, in perioral skin samples, we observed striated muscle fibers with their motor nerves and motor endplates. Our work provides the first morphological study of human facial cutaneous innervation, highlighting some unique features of this territory. Quantification of unmyelinated and myelinated fibers on 2-mm punch biopsies appeared to be feasible and reliable. Facial skin biopsy may be a new approach with which to study and to better characterize facial pain syndromes. [ABSTRACT FROM AUTHOR]

Neuropathic pain, i.e. pain arising as a direct consequence of a lesion or disease of the somatosensory system, affects about the 7 % of the general population. In this short review, we describe the most reliable laboratory tools for assessing neuropathic pain, such as quantitative sensory testing, laser-evoked potential recordings and skin biopsy, procedures that selectively assess nociceptive pathways. [ABSTRACT FROM AUTHOR]

Objective: To assess whether pain in the anterior-lateral part of the thigh in women affected by endometriosis is due to femoral nerve invasion by endometriotic implants. Design: Case-control study. Setting: Hospital. Patient(s): We enrolled 30 patients with endometriosis and leg pain in the anterior-lateral part of the thigh and 30 healthy women. Intervention(s): Skin biopsy and neurologic examination for detection of neuropathy. Main Outcome Measure(s): Intraepidermal small fiber density reduction and positive neurologic examination agree with sensitive neuropathy. Result(s): Biopsy results showed no statistically significant difference between the case group and the control group. At neurologic examination nine patients in the study group (30°/o) showed positive results, none in the control group showed signs. These nine patients had reduced intraepidermal small fiber density, compared to the lower cutoff values of the control group, suggesting a sensitive neuropathy. Conclusion(s): When there is leg pain in women with endometriosis it is important to distinguish neuropathic from referred pain. Skin biopsy and neurologic examination should be introduced in the management of leg pain in endometriosis, due to their low invasiveness to diagnose a sensitive neuropathy. As a result early detection of nerve injuiy and planning for a prompt specific treatment would be possible. [ABSTRACT FROM AUTHOR]

Although the most widely agreed neurophysiological tool for investigating small fiber damage is laser-evoked potential (LEP) recording, no study has documented its diagnostic accuracy. In this clinical, neurophysiological, and skin biopsy study, we collected age-corrected LEP normative ranges, verified the association of LEPs with pinprick sensory disturbances in the typical diabetic mixed fiber polyneuropathy, and assessed the sensitivity and specificity of LEPs in diabetic small fiber neuropathy. From 288 LEP recordings from the face, hand, and foot in 73 healthy subjects, we collected age-corrected normative ranges for LEPs. We then selected 100 patients with mixed-fiber diabetic neuropathy and 25 patients with possible small-fiber diabetic neuropathy. In the 100 patients with mixed fiber neuropathy, we verified how LEP abnormalities were associated with clinically evident pinprick sensory disturbances. In the 25 patients with possible pure small fiber neuropathy, using the skin biopsy for assessing the intraepidermal nerve fiber density as a reference standard, we calculated LEP sensitivity and specificity. In healthy participants, age strongly influenced normative ranges for all LEP variables. By applying age-corrected normative ranges for LEPs, we found that LEPs were strongly associated with pinprick sensory disturbances. In relation to the skin biopsy findings, LEPs yielded 78% sensitivity and 81% specificity in the diagnosis of diabetic small fiber neuropathy. Our study, providing age-corrected normative ranges for the main LEP data and their diagnostic accuracy, helps to make LEPs more reliable as a clinical diagnostic tool, and proposes this technique as a less invasive alternative to skin biopsy for diagnosing diabetic small fiber neuropathy. [ABSTRACT FROM AUTHOR]