Erythromelalgia as a form of neuropathy.
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Adult↗
Biomedical subjects
B L Munger
Publications and source records attributed to B L Munger.
The differentiation of the skin and its appendages. I. Normal development of papillary ridges.
In the present study, the normal development of papillary ridges was studied in the volar pads of both fore and hindpaws of the opossum, Monodelphis domesticus. At birth, the developmental state of the opossum's paws is equivalent to that of a six-week human embryo. The development of papillary ridges in the opossum occurs entirely postnatally and the hindpaw lags behind the forepaw by at least four days in most developmental parameters. Papillary ridge formation is preceded by four events: skin innervation, Merkel cell differentiation, mesenchymal condensation, and epidermal proliferation. The apical pads at the tips of the digits and the interdigital pads between the heads of the metacarpals (or metatarsals) have a unique pattern of innervation and mesenchymal content as compared to the non-pad skin. Each pad is innervated by a prominent nerve trunk and axons ascend towards the epidermis providing a density of innervation that exceeds that in the non-pad epidermis. Merkel cells are absent in non-pad epidermis but present in the pads prior to the onset of formation of papillary ridges. A loose aggregation of mesenchyme forms the core of the pads and the superficial dermis is more cellular in the pads as compared to the equivalent dermis in surrounding non-pad skin. Developing papillary ridges always contained Merkel cell-axon complexes. Merkel cell axon complexes serve as the anatomical substrate of slowly adapting (SA) mechanoreceptors. The presence of these complexes during early skin differentiation is consistent with the use of the opossum's forepaw in climbing to the nipple, but also suggests other possible functions. We hypothesize that the nervous system might play a role in the timing or patterning of the formation of papillary ridges.
Animals↗
The differentiation of the skin and its appendages. II. Altered development of papillary ridges following neuralectomy.
In order to test the hypothesis that the nervous system is an important determinant of skin differentiation, deletions of the left lumbosacral dorsal root ganglia (DRGs), the sources of cutaneous afferents to the left hindpaw, were performed on opossum pups at day 1 when hindpaws have just begun to be innervated. At birth, each lumbosacral DRG measures about 200 microns rostrocaudally and a deletion measuring 1 mm would span 4-5 DRGs. Following survival periods of 5-24 days, serial sections through the trunk documented partial left lumbosacral DRG deletion and a variable degree of spinal cord destruction. The blood supply to the trunk and hindpaws was preserved. Bilateral enlargement of residual DRGs was observed and regenerating skin at the site of the deletion was hyperplastic and hyperinnervated. The skin of the plantar pads of the hindpaws was studied following the neuralectomies. Statistically significant differences were observed between the left (experimental) and right (control) hindpaws. The density of innervation of the left hindpaw was reduced compared to the right hindpaw, development of papillary ridges was retarded by 3-4 days, and non-innervated Merkel cells were hypogranulated. This period of delay in ridge development is probably a reflection of the expansion of residual DRGs into the peripheral domains of deleted DRGs. The present study confirms a role for afferent nerves in the timing of cutaneous differentiation and a mutual trophic dependence between cutaneous nerves and Merkel cells in the epidermis.
Animals↗
An experimental painful peripheral neuropathy due to nerve constriction. I. Axonal pathology in the sciatic nerve.
A constriction injury to the sciatic nerve of the rat produces a painful peripheral neuropathy that is similar to the conditions seen in man. The pathology of the sciatic nerve in these animals was examined at 10 days postinjury, when the abnormal pain sensations are near maximal severity. The nerves were examined with (1) complete series of silver-stained longitudinal sections of pieces of the nerve (3 cm or more) that contained the constriction injury in the center, (2) toluidine blue-stained semithin sections taken at least 1 cm proximal and 1 cm distal to the constriction, and (3) EM sections taken adjacent to those stained with toluidine blue. One centimeter or more proximal to the constriction, both myelinated and unmyelinated axons were all normal. Nearer to the constriction, extensive degeneration of myelinated axons became increasingly common, as did signs of endoneurial edema. Distal to the constriction, the nerve was uniformly edematous and full of myelinic degeneration. There was a profound loss of large myelinated axons and a distinctly less severe loss of small myelinated and unmyelinated axons. These observations show that at 10 days postinjury the constriction produces a partial and differential deafferentation of the sciatic nerve's territory. The absence of degeneration in the nerve 1 cm proximal to the constriction indicates the survival of the primary afferent neurons whose axons are interrupted.
Animals↗
Intravascular plastic catheters. How they potentiate tumor necrosis factor release and exacerbate complications associated with sepsis.
We tested the hypothesis that long-term intravascular cannulation exacerbates the harmful effects of an infectious challenge. Four groups of rats were initially studied: rats without intravascular catheters or infection (group 1), rats without catheters with a polymicrobial infection (group 2), rats with catheters but no infection (group 3), and rats with catheters and infection (group 4). Infected animals had an increased mortality and generated a significantly increased tumor necrosis factor response compared with noninfected animals. Animals with catheters and infection generated far less cardiac output than animals from the other three groups. No histologic changes differentiated the four groups. Therefore, the presence of a sterile intravascular catheter significantly increases cardiac dysfunction and mortality rates in rats with chronic bacteremia. These results suggest that intravascular plastic catheters potentiate the destructive cascade of events produced by the host in response to bacteremia.
Abscess↗
Differentiation of the anterior body wall and truncal epidermis and associated co-migration of cutaneous nerves and mesenchyme.
The present study examines the relationship between the migration of mesenchyme and associated cutaneous nerves that are involved in the closure of the anterior body wall in embryonic mice and rats by light and electron microscopy. The sternum is formed by the migration of condensations of mesenchyme originating in the dorsolateral body wall known as sternal bands. In the course of analyzing this process in rodent embryos we have identified similar paired caudal extensions of the sternal bands that are responsible for the closure of the abdominal wall following resolution of the umbilical hernia, and we suggest these bands of mesoderm should be referred to as the abdominal bands. Both the sternal and abdominal bands are associated with the development of the segmental spinal nerves and their cutaneous terminal branches. The first cutaneous nerve to reach the skin surface in rats is the later cutaneous nerve (PCN and ACN) at E13.5 days. The ACN co-migrates with the sternal and abdominal bands, and terminal branches of axons from the ACN approach the epidermis during this migration. Differentiation of the epidermis could be recognized as a change in shape of epidermal cells from squamous to cuboidal, and this initial differentiation coincides with the onset of cutaneous innervation, beginning at the site of the LCN and following the extent of innervation of the PCN as well as the migration of the mesodermal bands and associated ACN. The paired ACN's meet in the ventral midline at E16.5 in rats as the sternal bands fuse, and terminal axons from both nerves densely innervate the midline skin.(ABSTRACT TRUNCATED AT 250 WORDS)
Abdominal Muscles↗
Neuro-cutaneous interactions in embryonic development: implications for medical dermatoglyphics.
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Animals↗
The development of Meissner corpuscles in primate digital skin.
Digital skin from fetal and neonatal primates was examined using light and electron microscopic techniques to document the development of the Meissner corpuscle. Generation of the receptor was initiated early in the third trimester by fine neurites which left the superficial dermal nerve plexus, ascended the dermal papillae and entered the basal epidermis. As maturation of the Meissner corpuscle continued, the axons were confined to the apex of the dermal papilla, where they were oriented parallel to the surface to the surface of the skin and terminated among cytoplasmic extensions of presumptive lamellar cells. During late fetal life the complexity of the lamellar cell stacking increased and the lamellar cell bodies were found solely at the base of the receptor. Numerous axon terminals were evident between the cytoplasmic lamellae. The appearance of the neonatal Meissner corpuscle was indistinguishable from that of the adult, indicating that the complete cycle of development is concluded before birth.
Animals↗
Myotome and early neurogenesis in chick embryos.
The present study was undertaken in order to verify the identification of profiles of presumptive growth cones in vivo. The developing spinal nerves of chick embryos were studied by light and electron microscopy. We traced the onset of efferent and afferent innervation of the myotome in 2- to 4-day-old chick embryos in order to be sure that we were examining the growing tips of axons. In the process of studying these growing axons, we were able to observe some unique relationships of neural tube, myotome, and differentiating spinal nerves. The neural tube tightly abuts the myotome in Hamburger and Hamilton's (HH) stage 14 chick embryos and cytoplasmic projections from the myotome directly abut the neural tube. The first ventral roots could be identified in HH stage 15 embryos and dorsal roots in HH stage 16 embryos, both under 2 1/2 days of age. The advancing spinal nerve courses toward the anterior or cranial half of the myotome, and growth cones directly contact the medial wall of the myotome. The spinal nerves continue to abut tightly the myotome during the succeeding day of embryonic life, and growth cones enter the substance of the myotome by 3 days, or HH stage 19 embryos. These dorsolaterally directed axons will form the dorsal ramus of the spinal nerves and the ventral ramus continues to be contiguous with the myotome. Invasion of the myotome by axons (putative innervation), and thus innervation of myotomal cells in the 3-day chick embryos, was a totally unexpected finding. The myotome and its potential derivatives thus have extensive neural contact by 3 days of embryonic life in the chick. These findings document a parallel differentiation of afferent and efferent elements of the nervous system and confirm previous accounts identifying growth cones in an intact organism. These findings suggest that afferent as well as efferent nerves may have critical roles in the differentiation of the mesodermal as well as ectodermal derivatives.
Animals↗
The early ontogeny of the afferent nerves and papillary ridges in human digital glabrous skin.
The present study examines the early ontogeny of afferent nerves in human embryonic glabrous digital skin and documents the onset of cutaneous innervation and papillary (sweat duct) ridge formation by light and electron microscopy. The skin examined in this study was taken from 3 developmental stages of decreasing embryonic age: embryos older than 10 weeks estimated gestational age (EGA) representing the period of primary ridge formation, embryos of 8-9 weeks EGA representing the period immediately prior to ridge formation; and embryos 6-8 weeks EGA representing the period weeks before the onset of ridge formation. The earliest papillary ridges are present in 10 week EGA embryos, with small ridges present in two sites: the center of the proximal third and also at the tip of the distal phalangeal or apical pad. These papillary ridges typically contained Merkel cells. Papillary ridges formed progressively in a radial manner from these central foci. The proximal focus corresponds to the geometric center of the mature dermatoglyphic pattern of loops, arches, or whorls. This radial wave of ridge differentiation is discontinuous with the abrupt cessation of ridge formation responsible for the discontinuities in the mature papillary ridges and the corresponding dermatoglyphic print. Skin over the proximal and middle phalanges developed papillary ridges beginning in the 12th week. No papillary ridges could be identified in embryos of 8-9 weeks EGA, but a large number of growth cones are present in the superficial dermis subjacent to differentiating Merkel cells. The basal lamina of the epidermis was discontinuous wherever growth cones abutted Merkel cells. Merkel cells not directly associated with axons were also present in the epidermis of embryos of 8-9 weeks EGA. The embryos of 6-8 weeks EGA lack any sign of Merkel cells and/or melanocytes, but developing neurovascular bundles with axonal growth cones near the epidermis could be identified by light and electron microscopy. Presumptive Schwann and perineural cells are also seen in the dermis. We conclude that the developing afferent nerve fibers provide a grid which influences the temporal and/or spatial factors involved in the sequential onset and cessation of formation of papillary ridges. Thus the dermatoglyph can reflect the ontogeny of the afferent nervous system that occurred prior to papillary ridge development. These observations lend support to the concept that successive waves of afferent neural development have an important role in the spatial and temporal sequence of papillary ridge formation and thus the formation of both the dermatotopic map of the digits and the dermatoglyph.
Embryonic and Fetal Development↗
Degeneration and regeneration of peripheral nerve in the rat trigeminal system: III. Abnormal sensory reinnervation of rat guard hairs following nerve transection and crush.
The present study was undertaken in an attempt to better understand the abnormalities of cutaneous sensibility that are present in patients following nerve injury with concomitant cutaneous denervation and subsequent reinnervation. Reinnervated intervibrissal pelage of the rat mystacial pad was studied in silver-impregnated sections 3 and 5 months after transecting and 2 and 5 months after crushing the infraorbital nerve. The sensory terminals on guard and vellus hairs were analyzed in serial paraffin sections and in thick frozen sections. In normal rat mystacial skin, approximately nine/ten of innervated guard hairs have a typical piloneural complex consisting of a palisade of highly regular lanceolate terminals surrounded by circularly arranged Ruffini terminals and free nerve endings (FNEs). The remaining one of ten innervated guard hairs has only circularly arranged presumptive FNEs and Ruffini terminals. Vellus hairs, either singly or in clusters, typically have only circularly arranged terminals that in many cases are simple FNEs. We first recognized abnormalities in innervation of hairs following nerve transection and fully expected nerve terminals to be completely normal following nerve crush. Almost all reinnervated sensory nerve terminals associated with guard hairs were markedly abnormal following nerve transection and quantitatively abnormal following nerve crush. Following nerve transection, lanceolate terminals were almost completely absent, and they were remarkably reduced in number following nerve crush. Vellus hairs when reinnervated typically lacked the complex circular presumptive Ruffini terminals. These findings may be in part the basis for the abnormal cutaneous sensory perceptions (dysasthesias and paresthesias) noted in human subjects following damage to nerves with subsequent sensory reinnervation of the skin.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Membrane relationships in murine Meissner corpuscles: cytology of freeze-substituted tissue.
Mechanoreceptive sensory corpuscles (murine Meissner corpuscles) in the toe pad skin of mice, consisting of axon terminals and lamellar cells, were studied following freeze-substitution in order to clarify the plasma membrane relationships between axon terminals and lamellar cells. Tissue preservation of corpuscles was excellent when the corpuscle was located within 10 microns from the contact surface with the precooled metal block. The axolemmata appeared more electron-opaque than did plasma membranes of lamellar cells. The inner leaflet of the unit membranes was thicker than the outer leaflet in the axolemma, and the contour of cell plasma membranes was relatively smooth and straight. Characteristic focal or regional approximations of plasma membranes were noted between the axon and abutting lamellae. Such membrane appositions resembled gap junctions, although no gap junctions were found between the axon and lamellae in chemically fixed materials. Similar gap junction-like close appositions of plasma membranes also were found between neighboring lamellae. These approximations occurred more frequently than typical gap junctions seen in chemically fixed materials. These findings indicate that there may be a relationship of the plasma membranes in the axon terminals and in abutting lamellae as well as between neighboring lamellae that have not been identified as yet in conventional chemically fixed material. Another striking finding was that basal laminae on lamellar cells exhibited the same electron opacity as the surrounding connective tissue matrix and thus the two are indistinguishable from one another. Furthermore, the lamina lucida was not evident, and basal lamina material was directly contiguous with the plasma membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The morphogenesis of the posterior neural tube and tail in Monodelphis domesticus.
The process of secondary neuralation has been studied in the Brazilian opossum, Monodelphis domesticus. Secondary neuralation in this mammal was found to have qualities of secondary neuralation that were present in both the chick and the mouse. In this study, four stages of secondary neuralation were found beginning with the medullary cord stage. Other stages in the differentiation of the secondary neural tube were: differentiation of the neuroepithelium, cavitation of the medullary cord, and proliferation of the neural tube. The process of secondary neuralation proceeded in a rostral-to-caudal direction and was found to be independent of age. Diastematomyelia (doubling of the tube) was found in several animals. The process of cavitation was completed by the joining of several small, focal cavities in a rostral-to-caudal direction. The most distinctive feature of secondary neuralation in this animal was the finding of axons within the secondary neural tube, a feature not characteristic of either the chick or the mouse.
Animals↗
The reinnervation of denervated skin.
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Animals↗
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)
Animals↗
Neurophysiologic aspects of allogeneic skin and upper extremity composite tissue transplantation in primates.
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Animals↗
The enigma of sensitivity in Pacinian corpuscles: a critical review and hypothesis of mechano-electric transduction.
The present report reviews the physiological and morphological specializations of Pacinian corpuscles and other mechanoreceptors that are present in the skin and connective tissues of the body as well as the cochlea. The remarkable sensitivity of Pacinian corpuscles is such that the only form of mechanical energy that could be perceived by a Pacinian corpuscle is a sound wave. In fact the human finger as demonstrated by Munger and Ide (1987) can perceive sound waves when water is the coupling agent. The structural specializations are equally remarkable with extensive membrane specializations of both the inner core and inner portion of the outer core. The halves of the inner core are each coupled with gap junctions and the inner portion of the outer core joined with numerous tight junctions. The cleft regions have specializations involving the axolemma that consist of numerous axonal spines containing bundles of filaments projecting into the cleft of the inner core. These structural specializations are thought to represent specializations for mechano-electric transduction analogous in many respects to the hair cells of the cochlea. A hypothesis for mechano-electric transduction is presented that may account in part for the extreme sensitivity of Pacinian corpuscles and other mechanoreceptors.
Animals↗
A cytologic study of Grandry corpuscle development in chicken toe skin.
The developmental sequence of Grandry corpuscles was traced in the toe skin of embryonic, young and adult chickens by light and electron microscopy. The developing Grandry cells as well as Schwann cells can first be identified at stage 38 (approximately 12 days of incubation) due to the cytoplasmic content of scattered secretory granules of approximately 100 nm in diameter. Such developing Grandry cells are always associated with nerve fibers. During late stages (stages 40-42, 14-16 days of incubation) several immature Grandry cells formed cell clusters in the dermis. Such cell clusters were always in contact with growing nerve tips of Schwann cells. Immature Grandry cells were separated from one another and dispersed in the connective tissue compartment at stages 44-45 (near hatching). By the time of hatching the developing Grandry cells began to have the morphological characteristics of adult cells. They were relatively large in cell diameter (approximately 10 micron) containing numerous secretory granules and bundles of filamentous material. These cells had finger-like cytoplasmic processes. The Grandry cells at this time had an intimate relationship with nerve fibers and satellite cells. The fact that Grandry cells were always associated with nerve fibers throughout development would support the hypothesis that Grandry cells are derived from neural elements, perhaps neural crest. Satellite cells of Grandry corpuscles are apparently derived from Schwann cells. Grandry cells and corpuscles are adult in form by two to three months of age.
Animals↗