The epidermis is innervated by fine nerve endings that are important in mediating nociceptive stimuli. However, their precise role in neuropathic pain is still controversial. Here, we have studied the role of epidermal peptidergic nociceptive fibers that are located adjacent to injured fibers in a rat model of neuropathic pain. Using the Spared Nerve Injury (SNI) model, which involves complete transections of the tibial and common peroneal nerve while sparing the sural and saphenous branches, mechanical hypersensitivity was induced of the uninjured lateral (sural) and medial (saphenous) area of the foot sole. At different time points, a complete foot sole biopsy was taken from the injured paw and processed for Calcitonin Gene-Related Peptide (CGRP) immunohistochemistry. Subsequently, a novel 2D-reconstruction model depicting the density of CGRP fibers was made to evaluate the course of denervation and re-innervation by uninjured CGRP fibers. The results show an increased density of uninjured CGRP-IR epidermal fibers on the lateral and medial side after a SNI procedure at 5 and 10 weeks. Furthermore, although in control animals the density of epidermal CGRP-IR fibers in the footpads was lower compared to the surrounding skin of the foot, 10 weeks after the SNI procedure, the initially denervated footpads displayed a hyper-innervation. These data support the idea that uninjured fibers may play a considerable role in development and maintenance of neuropathic pain and that it is important to take larger biopsies to test the relationship between innervation of injured and uninjured nerve areas.

No abstract

The POU domain transcription factor Oct-6 is a major regulator of Schwann cell differentiation and myelination. During nerve development and regeneration, expression of Oct-6 is under the control of axonal signals. Identification of the cis-acting elements necessary for Oct-6 gene regulation is an important step in deciphering the complex signalling between Schwann cells and axons governing myelination. Here we show that a fragment distal to the Oct-6 gene, containing two DNase I-hypersensitive sites, acts as the Oct-6 Schwann cell-specific enhancer (SCE). The SCE is sufficient to drive spatially and temporally correct expression, during both normal peripheral nerve development and regeneration. We further demonstrate that a tagged version of Oct-6, driven by the SCE, rescues the peripheral nerve phenotype of Oct-6-deficient mice. Thus, our isolation and characterization of the Oct-6 SCE provides the first description of a cis-acting genetic element that responds to converging signalling pathways to drive myelination in the peripheral nervous system.

In the carpal tunnel anatomical interconnections between the tendons of the musculus flexor digitorum profundus are systematically present. These interconnections limit the mutual tendon displacements, which decreases finger independence and may be problematic in a musician’s hand. The present study investigates a possible role of the synovial sheaths in the formation of these intertendinous connections in the carpal tunnel. To this end a morphological model is provided which correlates the often distinctly fibrous structure of the deep flexor tendons in the carpal tunnel and the frequent exchange of tendon fibres between the tendons to the different fingers, with the tendency of the synovial membranes to strongly adhere to the tendons. This model is validated by gross dissection results, and by cross sections of the flexor tendons in the carpal tunnel. In agreement with the model, the anatomic data show that the synovial membranes tend to invade and become trapped in tendons made up from individualised tendon strands, and also strongly adhere to the substantial amounts of tendon fibres which may be exchanged between the flexor tendons proximal to the lumbrical origins. These fibres and the synovial membranes may form a strong fabric able to withstand substantial stretching forces of interconnected oppositely pulled flexor tendons.

The mechanical interactions of tendon loading and motion between FDS and FDP tendons and the distal edge of the A2-pulley (DEA2) were investigated in cadaveric hands. The FDP tendon showed a two-stranded contrarotational spiral of tendon fibres, their course parallel to the FDS fibres. On loading, the FDP tendon changed cross-sectional shape and the two slips of FDS moved closer together, applying lateral force on the FDP tendon. The formula DEA2-MCP/proximal phalanx length was calculated as 0.64 +/- 0.052 mm/mm. Excursions of bifurca and chiasma were measured relative to the DEA2. In full extension the bifurca was well proximal to the DEA2, the chiasma always distal. In flexion, the chiasma approximated to DEA2 level. Therefore, an additional anteroposterior force should exist at DEA2 level between FDS and the DEA2 on the FDP-tendon. The changes in tendon shape and the lateral- and anteroposterior forces produce a "compressional" mechanism on FDP by FDS which may alter frictional resistance. This mechanism is compared with the Chiropteran tendon locking mechanism.