Immunohistological demonstration of S-100 protein in the cutaneous nervous system

S-100 protein, isolated from mammalian brain, has widely been used for immunohistochemical marker of the glia cells and the cells derived from the neural crest. In the present study, we made anti S-100 protein antibody and studied the immunoreactive distribution of S-100 protein in the cutaneous nervous system. Albino rabbits were immunized with S-100 protein and complete Freund adjuvant, and antiserum was purified by ion-exchange chromatography. Formalin-fixed normal human skin and sciatic nerve of rat were examined by the PAP method. S-100 protein was detected in Schwann cells of sciatic nerve of rat and cutaneous nerve bundles of human skin specimens. Meissner corpuscles and inner core cells of Pacinian corpuscles of human skin were S-100 protein positive. These findings suggest that the staining of S-100 protein with PAP method is a simple and reliable method to demonstrate the cutaneous nervous system. Also, lamellar cells of Meissner corpuscles and inner core cells of Pacinian corpuscles are indicated to be Schwann cell origin.     

Myelin basic protein-positive nerve fibres in human Meissner corpuscles

Myelinated nerve fibres forming sensory corpuscles become amyelinic before entering the corpuscle. Interestingly, in Meissner corpuscles from monkey myelin basic protein (MBP), a specific component of myelin sheath co-localized with neuronal markers. To investigate whether or not this also occurs in human digital Meissner corpuscles, we used single and double immunohistochemistry to detect MBP associated with axonic (protein gene product (PGP) 9.5) or Schwann and Schwann-related cell (S100 protein) markers. We also studied these markers in Pacinian corpuscles. Nerve fibres immunoreactive for MBP were detected in about 25% of the Meissner corpuscles examined; however, MBP never co-localized with PGP 9.5 and MBP occasionally co-localized with S100 protein. MBP-immunoreactive fibres associated with Meissner corpuscles were observed at the periphery of the lamellar cells or within the corpuscle between the lamellar cells. These results describe the distribution of myelinated nerve fibres expressing MBP in human Meissner corpuscles, which is important when studying Meissner corpuscles in cutaneous biopsies used for the diagnosis of peripheral and degenerative neuropathies.     

Immunohistochemical localization of laminin and type IV collagen in human cutaneous sensory nerve formations

We used immunohistochemical techniques and monoclonal antibodies to localize two basement membrane components (laminin and type IV collagen) in the nerves and sensory nerve formations, or corpuscles, supplying human digital skin. Furthermore, neurofilament proteins, S-100 protein and epithelial membrane antigen were studied in parallel. In dermal nerve trunks, immunostaining for laminin and type IV collagen was found to be co-localized in the perineurium and the Schwann cells, the stronger immunoreactivity being at the external surface of the cells. In the Meissner digital corpuscles, the immunoreactivity for laminin and type IV collagen was mainly observed underlying the cell surface of lamellar cells, while the cytoplasm was weakly immunolabelled or unlabelled. Finally, within Pacinian corpuscles co-localization of the two basement membrane molecules was encountered in the inner core, intermediate layer, outer core and capsule. Laminin and type IV collagen immunoreactivities were also found in blood vessels and sweat glands, apparently labelling basement membrane structures. The present results provide evidence for the presence of basement membrane in all periaxonic cells forming human cutaneous sensory nerve formations, and suggest that all of them are able to synthesize and release some basement membrane components, such as laminin and type IV collagen. The possible role of laminin in sensory nerve formations is discussed.     

Nerve growth factor receptor immunoreactivity in Meissner and Pacinian corpuscles of the human digital skin

The presence of nerve growth factor receptors (NGFr) in sensory nerve corpuscles of human digital skin, primarily Meissner and Pacinian corpuscles, was investigated immunohistochemically using two monoclonal antibodies directed against human-NGFr. To ensure the localization of NGFr immunoreactivity (IR) alternative sections to that processed for NGFr detection were assayed for neurofilament protein (NFP) and S-100 protein which selectively label the axon and the periaxonic specialized cells (lamellar cells of Meissner's corpuscles; inner-core cells of Pacinian corpuscles), respectively. Occurrence of NGFr IR was observed in both types of sensory corpuscles. In Meissner's corpuscles NGFr-IR was found in the lamellar cells, whereas in the Pacinian corpuscles the lamellae of the inner core, outer core, and capsule displayed NGFr IR. Moreover, a positive IR was observed in the central axon of some Pacinian corpuscles. However, remarkable differences were encountered among Pacinian corpuscles in the pattern of NGFr IR distribution. Present results demonstrate puscles in the pattern of NGFr IR distribution. Present results demonstrate the presence of NGFr IR in sensory nerve corpuscles of the human digital skin, suggesting that NGFr could be involved in the concentration of NGF and in the conveying of this molecule from the cutaneous sources to the cell body of NGF-dependent primary sensory neurons. However, the mechanisms involved in this process remain to be clarified. © 1993 Wiley-Liss, Inc.     

S100α and S100β proteins in human cutaneous sensory corpuscles: Effects of nerve and spinal cord injury

S100 protein in the vertebrate peripheral nervous system consists of homo- or heterodimers of S100α and S100β proteins, the first predominating in neurons and the second in glial cells. Recently, however, occurrence of S100β protein in neurons has been reported. The expression of S100 protein by Schwann cells, as well as their derivatives in sensory corpuscles, depends on the sensory axon (i.e., the Schwann cell–axon contact). The present study analyzed the distribution of S100α and S100β proteins in human cutaneous sensory corpuscles and the effects of peripheral or central sensory axon severance in the expression of these proteins. Simple or double immunohistochemistry was carried out using a panel of antibodies against S100α, S100β or S100α+β proteins, and the sections were examined by light or laser confocal scanning microscopy. Skin samples were obtained from normal subjects and patients with spinal cord injury, nerve entrapment, and nerve sections plus graft. The lamellar cells of Meissner corpuscles as well as the inner-core lamellae of the Pacinian corpuscles displayed strong immunoreactivity (IR) for all antigens examined, the most intense labeling being obtained for S100β protein. The pattern of immunostaining was unchanged after spinal cord injury, whereas the number of stained corpuscles as well as the intensity of IR for each antigen decreased in cutaneous sensory corpuscles after nerve injury, both entrapment and section plus graft. No evidence was found of axonal labeling. The present results provide evidence that Schwann-related cells in human cutaneous sensory corpuscles contain both S100α and S100β and that the expression of these proteins is dependent on the functional and structural integrity of sensory fibers. Anat. Rec. 251:351–359, 1998. © 1998 Wiley-Liss, Inc.     

Bcl-2 immunoreactivity in human cutaneous Meissner and Pacinian corpuscles

The occurrence and distribution of Bcl-2, a protein involved in the death-life cell pathways, was investigated in the peripheral sensory nervous system of healthy adult humans, including lumbar dorsal root ganglia, nerve trunks and glabrous skin (to analyze sensory corpuscles) using Western blot and immunohistochemistry. The antibody used labelled a protein of 26 kDa of estimated molecular weight corresponding with Bcl-2. Immunohistochemistry showed that only a neuronal population in dorsal root ganglia, some axons in peripheral nerves and the axon supplying Meissner and Pacinian corpuscles contained Bcl-2, whereas peripheral glial cells (i.e. satellite glial cells, Schwann cell, and lamellar cells of sensory corpuscles) did not. These results suggest that in normal conditions, Bcl-2 is only present in some neuronal, but not glial, elements of the sensory peripheral nervous system. The functional significance, if any, of these results remains to be determined.     

Development of Meissner‐like and Pacinian sensory corpuscles in the mouse demonstrated with specific markers for corpuscular constituents

The development of Meissner‐like and Pacinian corpuscles was studied in mice [from postnatal day (Pd) 0 to 42] by using immunohistochemistry for specific corpuscular constituents. The battery of antigens investigated included PGP 9.5 protein and neurofilaments, as markers for the central axon; S100 protein, vimentin, and p75^LNGFR protein, to show Schwann‐related cells; and epithelial membrane antigen to identify perineurial‐related cells. In Meissner‐like corpuscles immunoreactivity (IR) for neuronal markers was found by Pd7 and later. The lamellar cells of these corpuscles expressed first S100 protein IR (Pd7 to Pd42), then vimentin IR (Pd12 to Pd42), and transitory p75^LNGFR IR (Pd7 to Pd19–20). Vimentin IR, but not epithelial membrane antigen, was detected in the capsule‐like cells of the Meissner‐like corpuscles. On the other hand, the density of Meissner‐like corpuscles progressively increased from Pd0 to Pd19–20. Pacinian corpuscles were identified by Pd7. From this time to Pd42 the central axon showed IR for neuronal markers, and the inner core cells were immunoreactive for S100 protein. Moreover, vimentin IR was detected in the inner core cells by Pd19 and later. Unexpectedly, the central axons displayed S100 protein IR (from Pd7 to P28), while p75^LNGFR protein IR or epithelial membrane antigen IR were never detected. Taken together, and based on the expression of the assessed antigens alone, the present results suggest that the Meissner‐like and the Pacinian corpuscles in mice become mature around Pd19–Pd28 and Pd20, respectively. Furthermore, these results provide a baseline timetable for future studies in the normal or altered development of sensory corpuscles in mice since specific sensory corpuscles are functionally associated with different subtypes of sensory neurons the development of which is selectively disturbed in genetically manipulated mice. Anat Rec 258:235–242, 2000. © 2000 Wiley‐Liss, Inc.     

Chondroitin Sulfate in Human Cutaneous Meissner and Pacinian Sensory Corpuscles

Chondroitin sulfate is a glycosaminoglycan involved in maintaining the morphofunctional properties of the extracellular matrix in peripheral nerves, but its distribution in human sensory corpuscles is unknown despite the role of extracellular matrix in mechanotransduction and axonal guidance. In this study we used immunohistochemistry to analyze the distribution of chondroitin sulfate in human cutaneous Meissner and Pacinian corpuscles. Chondroitin sulfate expression was absent from Meissner corpuscles. In Pacinian corpuscles chondroitin sulfate was found associated to a CD34 positive endoneurial-related layer, interposed between the S100 protein positive inner core cells, and the vimentin positive inner core and outer core-capsule cells. Therefore, the intermediate CD34+/chondroitin sulfate+ intermediate layer present in Pacinian corpuscles isolates the neural segment of the corpuscles (axon and inner core) from the non-neural segments (outer core and capsule). These results suggest a role of chondroitin sulfate in the proper axonal growth and guidance, within the neuronal compartment of the Pacinian corpuscles during development and reinnervation, can be hypothesized. Moreover, a role of CS in mechanotransduction cannot be ruled out. Anat Rec, 302:325–331, 2019. © 2018 Wiley Periodicals, Inc.     

Immunohistochemical localization of acid-sensing ion channel 2 (ASIC2) in cutaneous Meissner and Pacinian corpuscles of Macaca fascicularis

Acid-sensing ion channel 2 (ASIC2) is a member of the degenerin/epithelial sodium channel superfamily, presumably involved mechanosensation. Expression of ASIC2 has been detected in mechanosensory neurons as well as in both axons and Schwann-like cells of cutaneous mechanoreceptors. In these studies we analysed expression of ASIC2 in the cutaneous sensory corpuscles of Macaca fascicularis using immunohistochemistry and laser confocal-scanner microscopy. ASIC2 immunoreactivity was detected in both Meissner and Pacinian corpuscles. It was found to co-localize with neuron-specific enolase and RT-97, but not with S100 protein, demonstrating that ASIC2 expression is restricted to axons supplying mechanoreceptors. These results demonstrate for the first time the presence of the protein ASIC2 in cutaneous rapidly adapting low-threshold mechanoreceptors of monkey, suggesting a role of this ion channel in touch sense.     

p75 and TrkA neurotrophin receptors in human skin after spinal cord and peripheral nerve injury,with special reference to sensory corpuscles

Human skin, including nerves and sensory corpuscles, displays immunoreactivity (IR) for low- (p75) and high-affinity (TrkA-like) receptors for nerve growth factor (NGF), the best characterized member of the family of neurotrophins. This study was designed to analyze the changes induced by spinal cord and peripheral nerve injuries in the expression of neurotrophin receptors in digital skin, with special reference to nerves and sensory corpuscles. Skin biopsy samples were obtained from 1) the hand and toes of normal subjects, 2) below the level of the lesion of patients with spinal cord injury affecting dorsal and lateral funiculi, 3) the cutaneous territory of entrapped peripheral nerves (median and ulnar nerves), and 4) the cutaneous territory of sectioned and grafted nerves (median nerve). The pieces were formalin-fixed and paraffin-embedded, cut in serial sections, and processed for immunohistochemistry using antibodies against human p75 and TrkA proteins. The percentage of sensory corpuscles displaying IR for p75 and TrkA-like, as well as the intensity of IR developed within them, was assessed using quantitative image analysis. Spinal cord severance causes a decrease in p75 IR in Meissner and Pacinian corpuscles, whereas TrkA-like IR did not vary. In other nonnervous tissues (i.e., epidermis, sweat glands), both p75 and TrkA-like IR was diminished or even absent. Similar but more severe changes were encountered in the skin from the territory of entrapped nerves. Finally, in subjects with sectioned-grafted nerves, p75 IR was found close to controls in nerves, reduced in Meissner corpuscles, and absent in the inner core of the Pacinian ones; TrkA-like IR was in the perineurium, a small percentage of Meissner corpuscles (about 7%), and the outer core and capsule of the Pacinan corpuscles. In the nonnervous tissues, p75 IR was practically absent, whereas TrkA-like IR did not change. No changes in the expression of neurotrophin receptors were observed in Merkel cells of the different groups. Present results show the following: 1) expression of nerve p75 IR in human cutaneous sensory corpuscles is sensitive to central deafferentation, to blockade or difficulty in axonal transport, and to disruption of axonalcontinuity independently of possible restoration of axonal integrity due to grafts; 2) expression of TrkA-like IR in nerves and sensory corpuscles is sensitive only to nerve transection; 3) the corpuscular Schwann-related cells are the only cells involved in the above modifications, the perineurial cells remaining unchanged; 4) the expression of p75 and TrkA-like IR by Merkel cells is independent of normal innervation; 5) an adequate innervation of the skin seems to be necessary for the expression of p75 but not TrkA-like in nonneuronal cells, especially in the epidermis. A role for NGF in the maintenance of epidermis integrity is discussed. Anat. Rec. 251:371–383, 1998. © 1998 Wiley-Liss, Inc.     

Sensory Innervation of the Female Human Umbilical Skin: Morphological Studies

Background: Sensory stimuli are conducted by several cutaneous sensory nerves and tactile corpuscles. The latter are specialized sensory organs that represent the starting point of many afferent sensory pathways. To date, our knowledge about the distribution of the sensory innervation in the umbilical skin of females is incomplete.

Aim of the study: To elucidate the morphology of the cutaneous innervation of the normal female umbilical skin.

Materials and methods: Biopsies of normal umbilical skin were obtained from female patients undergoing umbilical hernial repair. The specimens were processed for both immunohistological (antibodies against PGP9.5, pan-neuronal marker, and S-100 protein, marker of Schwann cells) and ultrastructural (transmission electron microscopy) examinations.

Results: The authors found abundant genital end-bulb-like structures, numerous epidermal and dermal Merkel cells, Meissner and Ruffini corpuscles, intraepidermal nerve terminals, and multiple free nerve endings surrounding the ducts and acini of the sweat glands.

Conclusions: The umbilical skin of females has abundant sensory innervation similar to that of the glans penis.     

成人手指皮神经的免疫组织化学研究

采用 SP免疫组化的方法 ,研究 S— 10 0蛋白在人手指皮肤的感觉神经的表达情况 ,结果发现在每个真皮乳头嵴内都有 S— 10 0蛋白性标记物存在 ,标记出的结构是触觉小体。而环层小体则广泛分布在真皮网织层和皮下组织层。皮神经和其他感觉小体分布在血管和汗腺附近。本研究结果为探讨手指损伤后的感觉障碍和认识某些皮肤病的原因提供了实验资料。     

Tumour of Wagner-Meissner touch corpuscles*

Summary Two benign tumours composed mainly or exclusively of Wagner-Meissner corpuscles are described. In the first case the touch corpuscles are composed of closely piled laminar cells and surrounded by argyrophilic fibres. In the second case some Schwann cells are observed in between the tactile corpuscles. The light microscopic, electron-microscopic and immunohistochemical results demonstrate that these corpuscles are comparable with the tactile end organs of the skin. Immunohistochemically, neuron-specific enolase, vimentin and protein S-100 could be demonstrated in the tactile corpuscles. Neural processes present in normal Meissner corpuscles are absent and immunohistochemically no nerve fibres or nerve endings can be demonstrated using antibodies to neurofilaments as they are observed in normal touch corpuscles of the skin.Tumours which consist mainly of multiple touch corpuscles have not been described in the literature. It is suggested to call these tumours Wagner-Meissner neurilemmoma.Dedicated to Professor Dr. Dr. h.c. K. Lennert in honor of his 65th birthday     

Immunohistochemical localization of the high-affinity NGF receptor (gp 140-trkA) in the adult human dorsal root and sympathetic ganglia and in the nerves and sensory corpuscles supplying digital skin

Background: Nerve growth factor (NGF) is produced in target issues of sympathetic and neural-crest derived sensory neurons, including skin, to provide them trophic support. The biological effects of NGF on responsive cells are mediated by specific high-affinity receptors. Recently, a protein tyrosine kinase of ? 140 kDa molecular weight, encoded by the proto-oncogene trkA, has been identified as the high-affinity NGF receptor (gp140-trkA). The present work was undertaken to study the localization of gp140-trkA-like immunoreactivity (IR) in human peripheral ganglia (sympathetic and dorsal root ganglia), and in glabrous skin. Methods: Lumbar dorsal root ganglia, para- and prevertebral sympathetic ganglia, and digital glabrous skin were studied immunohistochemically using a rabbit anti-gp140-trkA polyclonal antibody. In order to accurately establish the localization of gp140-trkA IR, the neurofilament proteins and S-100 protein were studied in parallel in: (1) sensory and sympathetic ganglia, to label neuron cell bodies and satellite or supporting cells, respectively; (2) human skin, to label axons, Schwann and related cells within nerves and sensory corpuscles. Moreover, a quantitative study (neuron size, intensity of immunostaining) was carried out on sympathetic and dorsal root ganglia neuron cell bodies. Results: A specific gp140-trkA-like IR was found in: (1) a subpopulation (65%) of primary sensory neuron cell bodies, including most of the largesized ones but also small- and intermediate-sized ones; (2) most of sympathetic neuron cell bodies (82%); (3) theineurial cell, Schwann cells, and large axons of the nerve trunks supplying digital skin; (4) the lamellar cells of Meissner corpuscles; (5) the central axon, inner-core, outer-core, and capsule of Pacinian corpuscles. In addition, the occurrence of gp140-trkA-like IR was observed in some non-nervous tissues of the skin, including epidermis (mainly in the basal layer), sweat glands, and arterial blood vessels. Conclusions: Present results provide evidence for the localization of gp140-trkA-like IR in: (1) nerve cells which are known to be NGF-responsive, and (2) non-nervous cutaneous tissues which are innervated by NGF-dependent peripheral neruons. These findings suggest that, in addition to the well-established role of NGF on sensory and sympathetic neurons, this neurotrophin may be able to regulate some other functions on non-nervous cell which are targets for NGF-dependent peripheral neurons. © 1994 Wiley-Liss, Inc.     

Heparan sulfate in human cutaneous Meissner's and Pacinian corpuscles

Heparan sulfate proteoglycans are pericellular/cell surface molecules involved in somatosensory axon guidance in the peripheral nervous system. However, the distribution of heparan sulfate proteoglycans in the extracellular matrix of human cutaneous sensory corpuscles is unknown. Immunohistochemistry and immunofluorescence assays were performed to define the localization of heparan sulfate proteoglycans in human cutaneous Meissner's and Pacinian corpuscles using two anti-heparan sulfate antibodies together with anti-S100 protein, anti-PGP9.5, anti-CD34 (to immunolabel basement membranes, Schwann cells, axon and the intermediate endoneurial layer of Pacinian corpuscles, respectively), anti-Type IV collagen, and anti-chondroitin sulfate antibodies. Heparan sulfate proteoglycans were colocalized with Type IV collagen in Meissner's corpuscles and were located in the outer core lamellae and capsule, but not in the inner core or the intermediate layer, in Pacinian corpuscles. Chondroitin sulfate was observed in the intermediate layer of Pacinian corpuscles but was never colocalized with heparan sulfate proteoglycans. The present results strongly suggest that heparan sulfate proteoglycans are associated with the basement membranes of the lamellar cells in Meissner's corpuscles and with the complex outer core capsule in Pacinian corpuscles. The functional significance of these results, if any, remains to be elucidated.     

Reinnervation of Pacinian corpuscles by CNS axons after transplantation to the dorsal column: incidence and ultrastructure

Summary We have investigated the capacity of injured axons in the spinal dorsal columns of young adult rats to reinnervate grafted Pacinian corpuscles. A branch of the hindlimb interosseous nerve with a group of crural Pacinian corpuscles attached to it was autotransplanted to the surface of the spinal cord and the nerve stump was implanted into the dorsal column. Two to three months later 16 grafts were removed for examination by light and electron microscopy. By 3 months after transplantation almost all Schwann cell columns of the grafted nerve branch were occupied by regenerated myelinated and unmyelinated axons. Of 41 corpuscles examined by electron microscopy 24 were reinnervated by 1–3 myelinated fibres which gave rise to multiple terminals in the inner core. The remaining corpuscles appeared to be denervated. Only two of the reinnervated corpuscles contained regenerated endings which reiterated the distinct ultrastructure of normal presynaptic terminals of CNS axons, characterized by clusters of lucent vesicles and paramembranous densities. All other corpuscles were reinnervated by terminals which resembled peripheral mechanosensory endings as they contained mitochondria and very few vesicles. One such corpuscle was coinnervated by small terminals filled with large dense cored vesicles. We assume that the majority of grafted Pacinian corpuscles have been reinnervated by dorsal column axons and that the regenerated terminals with the ultrastructure of peripheral mechanosensory endings derive from central axons of primary sensory neurons, which are apparently capable of constructing mechanosensory-like terminals in response to signals from the Pacinian corpuscles. The vesicle-filled endings are probably formed by second order sensory neurons, corticospinal neurons and small peptidergic neurons unable to adjust their terminals to the new target.     

Multiple innervation of rat pacinian corpuscles regenerated after neonatal axotomy

The regeneration of Pacinian corpuscles was studied on the crural interosseous membrane in rats in which the sciatic nerve has been crushed at birth. The original population of developing Pacinian corpuscles rapidly degenerated after neonatal axotomy. Subsequently, the regenerating axons induced the differentiation of corpuscles de novo.The first regenerating Pacinian corpuscles were found on the interosseous membrane 19 days after neonatal axotomy. Each was, as a rule, supplied by several regenerating axons and contained a rudimentary inner core enclosing the largest axon terminal. By day 40 postnatal, the regenerated corpuscles usually contained several axon terminals enclosed by 2–7 inner cores compressed within a common outer capsule. The majority of corpuscles remained polyaxonal and contained multiple inner cores up to at least 11 months. This is in contrast to normal corpuscles that have one terminal enclosed in an inner core and capsule.The mean number of regenerated Pacinian corpuscles was13.2 ± 1.3 (±s.e.; n = 5) at one to four months after axotomy, i.e. 27.5% of the mean number48.0 ± 1.3 (n = 5) corpuscles found on normal interosseous membranes. The number of regenerated axons of the interosseous nerve supplying the corpuscles was decreased to about 40% of the normal number. The regenerated corpuscles were small and the diameters of the regenerated axons were much reduced.The permanent polyaxonality of newly formed Pacinian corpuscles together with their small size and number is an example of an aberrant course of regeneration in the rat after axotomy performed during the critical perinatal period of development.     

Effects of different types of injury to the inferior alveolar nerve on the behavior of Schwann cells during the regeneration of periodontal nerve fibers of rat incisor

The present study reports on different regeneration patterns of axons and Schwann cells in the periodontal ligament of the rat incisor using immunohistochemistry of protein gene product 9.5 (PGP 9.5) and S-100 protein. Three kinds of injury (transection, crush and segmental resection) were applied to the inferior alveolar nerve. In normal animals, PGP 9.5- and S-100-immunoreactivities were detected in the axons and Schwann cell elements of periodontal Ruffini endings, respectively. They were restricted to the alveolus-related part, occurring only rarely in the tooth-related part and in the shear zone (the border between the alveolus-related and tooth-related parts). Both transection and segmental resection caused the complete disappearance of PGP 9.5-immunoreactive nerve fibers in the periodontal ligament, while a small number of them could be found following the crush injury. Regenerating PGP 9.5-reactive nerve fibers appeared at 5 days and 21 days following the transection and segmental resection, respectively. The regeneration of periodontal nerve fibers completed in a period of 21-28 days and 14-21 days following the transection and crush, respectively, but was not completed even at 56 days following the segmental resection. The behavior of Schwann cells during regeneration was similar after the different nerve injuries; spindle-shaped S-100-immunoreactive cells, presumably Schwann cells, appeared in the shear zone and the tooth-related part. These cells disappeared 5-7 days prior to the completion of the regeneration of axonal elements of the periodontal ligament following the transection and crush. Following the segmental resection, in contrast, spindle-shaped S-100-positive cells disappeared from the tooth-related part at 42 days, although the axonal regeneration of periodontal Ruffini endings proceeded even until 56 days. We thus conclude that the duration of the migration of Schwann cells depends on the state of the regeneration of axons.     

The structure and function of cutaneous sensory receptors

The present review of cutaneous sensory receptors begins with a consideration of free nerve endings (FNEs) that can be considered as sensory terminals evidencing the least structural specialization of the axon and associated cells. Using the criteria established by Kruger et al (1981), FNEs of both A delta and C fibers can be identified on the basis of ultrastructural characteristics that include an intimate relationship between axons and the associated epithelium, the lack of a complete Schwann cell investment, the accumulation of numerous vesicles and other cytoplasmic organelles, and for A delta terminals a 1:1 relationship between axon and investing Schwann cell. Using these criteria, the so-called genital end bulbs of the human glans penis are merely a skein of FNEs based on the ultrastructural study of Halata and Munger (1986). Hair follicles of most species studied to date (the exception being the rabbit and to some extent the guinea pig) are multiply innervated with lanceolate, Ruffini and FNEs. The lanceolate terminals are the rapidly adapting terminals that are numerous in guard hairs. Ruffini terminals of hairs resemble those of the periodontal ligament or joint capsules and both are remarkably similar to Golgi tendon organs in terms of ultrastructural characteristics. The key ultrastructural characteristic is the encircling of collagen bundles by axons and associated Schwann and connective tissue cells. Axons frequently enter the epidermis either to terminate as FNEs or become associated with Merkel cells in glabrous skin at the base of the papillary ridges or in clusters of Merkel cells in hairy skin in touch domes or Haarscheiben. Merkel cells have clusters of apparent secretory granules polarized toward the axon and the axon is typically a slowly adapting mechanoreceptor. The function of the granules is not known. Pacinian corpuscles are the largest of the corpuscular receptors of the dermis and are characterized by an elaborate inner core of stacks of numerous thin lamellae arranged in a bilaterally symmetrical manner. Based on the fact that the lamellae are coupled with gap junctions and the outer core lamellae isolated by numerous tight junctions, the authors have proposed that the unique ionic environment may be in part responsible for the remarkable sensitivity of Pacinian corpuscles (Munger and Ide, 1987). Meissner corpuscles are a typical corpuscular receptor of murine (Ide, 1976, 1977), marsupial and primate glabrous skin (Munger, 1971). The axons typically weave back and forth between stacks of lamellae.(ABSTRACT TRUNCATED AT 400 WORDS)     

Reinnervation of transplanted Pacinian corpuscles by ventral root axons: Ultrastructure of the regenerated nerve terminals

Summary This study addresses two questions. Can mature, denervated and transplanted Pacinian corpuscles accept innervation from motor axons? If so, does the alien target influence the structural characteristics of the regenerated motor axon terminals? Pacinian corpuscles from the hind leg of young rats, together with a segment of the nerve branch through which they receive their sensory innervation, were autotransplanted to the surface of the spinal cord and the nerve stump anastomosed to the central stump of a transected lumbar ventral root. Between 4 and 5 months later the grafts were studied by electron microscopy. Ventral root axons regenerated through the endoneurial tubes of the grafted nerve to reach the corpuscles, most of which became reinnervated by one to three myelinated fibres. The fibres lost their myelin sheaths before entering the inner core, branched, and gave rise to multiple terminals in the inner core. The regenerated terminals were packed with spherical synaptic vesicles and closely resembled normal motor nerve terminals. Thus motor axons are able to reinnervate Pacinian corpuscles but the structural characteristics of the terminals are apparently not modified by the alien target tissue. This finding contrasts with previous studies, in which it was found that terminals of the central axons of large dorsal root ganglion cells, induced to reinnervate Pacinian corpuscles, displayed the structural characteristics of peripheral sensory endings rather than those of dorsal root terminals in the spinal cord.