Topography and ultrastructure of sensory nerve endings in the glans penis of the rat.

The aim of the present study was to describe the types and location of sensory nerve endings in the glans penis of the rat on the basis of light and electron microscopy. Free nerve endings are abundant throughout the glans and are derived from either thinly myelinated A delta or unmyelinated C fibers. The free nerve endings derived from A delta fibers often extend into the epidermis as far as the granular layer and exhibit buttonlike terminal thickenings. The distal urethra contains many free nerve endings from C fibers. Numerous lamellated corpuscles are present. Each corpuscle, innervated by one or two medium diameter myelinated nerve fibers, consists of 4-10 spiralling and intertwined inner cores enveloped by Schwann cell lamellae. The corpuscles are usually enclosed by a perineural capsule, although some located near the epidermis lack a capsule. Lamellated corpuscles in the superficial dermis are located adjacent to but not directly under a penile spine and change their orientation when the glans is erect. The dermal papillae of the penile spines are devoid of any neural structure. Lamellated corpuscles are also located within the trabeculae of the corpus spongiosum glands and in the lamina propria of the urethra. Occasionally, unmyelinated nerve bundles are seen inside these corpuscles. Ruffini corpuscles are few in number and are located in the deep connective tissue near the os penis. They have an incomplete connective tissue capsule and the nerve terminals are anchored between collagen fiber bundles. No Merkel nerve endings, Meissner, or Vater-Pacini corpuscles were found in any of the sections. We conclude that the glans penis of the rat contains a sensory receptor complement that is generally similar to the human glans penis but is unlike the glabrous and hairy skin.     

The sensory innervation of primate facial skin. II. Vermilion border and mucosa of lip

The innervation of the vermilion border and mucosa of the monkey lip have been studied by light and election microscopy. Meissner corpuscles are present at the junction between hairy skin and vermilion border usually high in the dermal papillae, tightly abutting the overlying basal layer of the keratinized squamous epithelium. These Meissner corpuscles resemble those described in primate glabrous skin and are characterized by the presence of stacks of lamellae interposed between loops of the terminal axon. The lamellae are cytoplasmic extensions of specialized Schwann cells referred to as lamellar cells. One to three myelinated axons, 2–4 μm in diameter, innervate a single Meissner corpuscle.Coiled simple corpuscles, innervated by 1–3 myelinated axons, 3–5 μm in diameter, are characteristic of the non-keratinized portion of vermilion border and oral mucosa. The terminal axons in simple corpuscles are enveloped by circumferentially arranged cytoplasmic lamellae. Small terminal axoplasmic spikes protrude into spaces between the cytoplasmic lamellae in both Meissner and simple corpuscles. Cytoplasmic lamellae in both receptors are characterized by the presence of numerous pinocytotic vesicles. The lower parts of Meissner as well as simple corpuscles are encapsulated by perineurium and these perineural epithelial cells have incomplete basal lamina on both sides of their flattened cytoplasm. In contrast, corpuscles that are present high in the dermal papillae have scant perineural capsular elements and instead have fibroblast-like cells demarcating the inner core of the corpuscle from the general connective tissue compartment. Endoneural fibroblasts are a constant component of all corpuscular receptors. Tactoids of fibrous long-spacing collagen are present in the endoneural connective tissue of these sensory corpuscles. The vermilion border has 10–20 corpuscular receptors per mm² of surface area. Tastscheiben consisting of clusters of Merkel cells and their associated axons are present in the basal layer of rete ridges and rete pegs throughout the hair skin, vermilion border, and oral mucosa of the primate lip.Free nerve endings (FNE's) have been identified using cytologie criteria described previously⁵⁴. FNE's in the vermilion border and mucosa often establish intimate contact with the basal lamina and/or basal cells of the epithelium. FNE's can also be identified in dermal papillae that contain Meissner and/or simple corpuscles. Ruffini nerve endings are not present in dermal papillae. This relatively dense sensory innervation can be correlated with the known tactile sensitivity of the lip in terms of twopoint as well as force thresholds and expanded areas of thalamic and cortical representation.The innervation of glabrous skin resembles that of hairy skin with Meissner and simple corpuscles of glabrous skin being equivalent to lanceolate terminals of hairy skin. The other sensory terminals of each type of skin are identical. Hairs provide an anatomical substrate for multiple afferent terminals, and rete ridges/dermal papillae are the equivalent structural unit in glabrous skin. Each cutaneous anatomical site can be multiply innervated, and this afferent information is processed centrally over multiple parallel ascending systems.     

Innervation of the digit on the forepaw of the raccoon

The innervation of the digits on the raccoon forepaw was examined by using immunochemistry for protein gene product 9.5, calcitonin-gene related peptide, substance P, neuropeptide-Y, tyrosine hydroxylase, and neurofilament protein. The larger-caliber axons in the ventral glabrous skin terminate as Pacinian corpuscles deep in the dermis, small corpuscles and Merkel endings around the base of dermal papillae, and Merkel endings on rete pegs in dermal papillae. Extensive fine-caliber innervation terminates in the epidermis and on the microvasculature. The innervation is more dense in the distal than in the proximal volar pads. Pacinian endings are also concentrated in the transverse crease separating the distal and proximal pads. In the dorsal hairy skin, hair follicles are well innervated with piloneural complexes. Merkel innervation is located under slight epidermal elevations and in some large Merkel rete pegs located at the apex of transverse skin folds just proximal to the claw. No cutaneous Ruffini corpuscles were found anywhere on the digit. The claw is affiliated with dense medial and lateral beds of Pacinian endings, bouquets of highly branched Ruffini-like endings at the transition from the distal phalanx and unmyelinated innervation in the skin around the perimeter. Encapsulated endings are located at the lateral edge of the articular surface of the distal phalanx. Extensive fine-caliber innervation is affiliated with sweat glands and with the vasculature and is especially dense at presumptive arteriovenous sphincters. Virtually all of the sweat gland and vascular innervation is peptidergic, whereas most of the unmyelinated epidermal innervation is nonpeptidergic.     

The innervation of the primate fungiform papilla — development, distribution and changes following selective ablation

The development of the terminal parts of the chorda tympani nerve, lingual nerve and cranial sympathetics in the macaque fungiform papillae were studied by light- and electron microscopy. Their respective distributions in the intra- and extragemmal compartments of papillae from adult macaques were examined following selective ablation of each nerve.Prior to midgestation, a single bundle of unmyelinated axons which contained numerous axoaxonic synapses passed through the subepithelial connective tissue and ramified in the single nascent chemosensory corpuscle and surrounding non-gustatory epithelium. Following midgestation

1. (1), additional chemosensory corpuscles appeared, possibly by division of existing corpuscles,

2. (2) myelination of axons was begun,

3. (3) axoaxonic synapses were eliminated, and

4. (4) nerve terminals appeared in the subepithelial connective tissue as free nerve endings and coiled simple nerve endings. In the perinatal period, coiled simple endings, corpuscular receptors and Meissner corpuscles were present in the papilla core. Large numbers of intra-epithelial nerve endings were present in the extragemmal epithelium throughout development. Tonofilament collars ensheathed intra-epithelial axons and 80–100 nm dense core granules, occupying adjacent epithelial cells, appeared to be sequestered near such axons.

Experimental selective ablation indicated that the terminal parts of chorda tympani fibers were present only within chemosensory corpuscles. In contrast, lingual nerve endings were present both in the extragemmal epithelium and chemosensory corpuscles and also were the sole supply of corpuscular receptors. Sympathetics appeared to be sparsely distributed in the papilla core.Intra-epithelial axons degenerated within 24 h following transection, while axons with Schwann or lamellar cell sheaths or myelin persisted for at least 3 days.     

The sensory innervation of primate facial skin. I. Hairy skin

The present study analyzes the variety of sensory nerve terminals present in the hairy skin of the monkey face. In addition to vellus hairs, guard hairs and sinus hairs, a unique type of sinus hair has been identified in the skin of the lip designated a hemisinus hair. Hemisinus hairs have a smaller blood sinus as contrasted to sinus hairs in that the sinus does not extend to the bulb of the hair follicle.Each type of hair of the face and the lip has its own distinctive pattern of innervation utilizing 5 identifiable unique nerve terminals: free nerve endings, Merkel, lanceolate, Ruffini, and finally, scattered corpuscular receptors at least in some sinus hairs. Hemisinus and guard hairs lack corpuscular receptors and thus can have 4 different terminals, although Merkel terminals are not consistently present in guard hairs. Vellus hairs have only 3 types of receptors: lanceolate, Ruffini and free nerve endings.Free nerve endings (FNE's) have been found in the connective tissue capsule of primate sinus and hemisinus hairs in the angle between the hair shaft and sebaceous gland and in the same site in guard and vellus hairs. Small diameter myelinated fibers branch and end blindly in the connective tissue or can be intimately associated with the sebaceous gland. FNE's are characterized by the presence of numerous mitochondria, occasional electron opaque lipoidal inclusions, granules of glycogen, a variable population of small vesicles, a tendency to a 1:1 relationship between Schwann cell and enveloped axon. The Schwann cell investment is often deficient with the axolemma directly abutting its basal lamina.Merkel cells and associated axons are present in rete ridge collars surrounding sinus and hemisinus hairs and in the external root sheath of these two types of sinus hairs. Hemisinus hairs have scant Merkel cells as compared to sinus hairs.Lanceolate terminals are arranged longitudinally with respect to the axis of the hair and abut the basal lamina of the external root sheath. Guard hairs have a complete palisade of 2–3 dozen lanceolate terminals; however, vellus hairs may have scant or no lanceolate terminals.Ruffini terminals can be identified on all 4 hair types. Some vellus hairs lack Ruffini terminals, whereas all sinus and hemisinus hairs and most guard hairs have Ruffini terminals. The ultrastructural as well as light microscopic criteria for the identification of each of these receptors has been described and discussed.     

Distribution and terminal arborizations of cutaneous mechanoreceptors in the glabrous finger pads of the monkey

Recent electrophysiological studies demonstrated that neurons in the somatosensory cortex of monkeys respond to tangential forces applied to glabrous skin. To unravel the peripheral basis for this cortical response, we determined the distribution of presumptive low-threshold mechanoreceptors innervating the distal finger pads of monkeys. Endings were reconstructed in immunolabeled serial sections imaged by epifluorescence and confocal microscopy. Although classically implicated as cutaneous stretch receptors, no Ruffini corpuscles were found in the glabrous skin. Ruffini-like endings were only detected at the base of the finger nails. Pacinian corpuscles were sparsely distributed in the deep dermis. Meissner corpuscles (MCs) in dermal papillary ridges had a comparably high density in the thumb, index, and fifth fingers. Each MC was innervated by several large-caliber axons. Within the limits of our reconstructions, some of these axons terminated in only one MC, whereas others innervated several MCs. Merkel endings covered about 80% of the base of the intermediate epidermal ridges that form the pattern of fingerprints. In some cases, the distal tip of a Merkel-related axon gave rise to a several terminal branches that supplied endings to tightly circumscribed (30-70 microm) clusters of Merkel cells. In other cases, the nodes of axons gave rise to en passant branches that formed extended chains of endings among Merkel cells spread over territories up to 300 microm long. Based on their relatively diffuse distributions, the axons that innervate multiple MCs or the axons with en passant Merkel terminations seem most suited to transduce tangential forces.     

Sensory nerve endings in rhesus monkey sinus hairs

The sensory innervation of primate sinus hairs has been studied by light and electron microscopy. For light microscopy paraffin sections as well as thick frozen sections were impregnated with silver and compared with serial semi-thin sections of tissue prepared for electron microscopy. One type of sensory terminal is present in the epidermis surrounding the hair follicle, and four specific nerve terminals have been identified within the blood sinus. An epidermal rete ridge collar encircles the hair shaft and contains ∽200 Merkel cellneurite complexes. Numerous other Merkel cell-neurite complexes are present in the external root sheath of the hair follicle beneath a thick glassy membrane innervated by ∽65 nerve fibers. At this level 10–15 lanceolate or palisade terminals are situated in the connective tissue. Up to 10 simple encapsulated corpuscles can be identified above the level of lanceolate endings and Merkel cell terminals. Ruffini corpuscles are closely applied to the glassy membrane below the lanceolate and Merkel terminals at the level where nerve fibers penetrate the capsule of the sinus. All of these terminals are supplied by 80–100 large diameter myelinated fibers distributed approximately as follows: 65 innervate Merkel cell-neurite complexes, 15 to lanceolate, 10 to simple corpuscles, and 10 to Ruffini corpuscles. The innervation of the rete ridge collar is independent of that of the sinus consisting of 10–12 fibers derived from the superficial dermal network. Each of these sensory terminals can be correlated with specific functional parameters as described in numerous neurophysiologic studies. Merkel cell-neurite complexes and Ruffini corpuscles are slowly adapting receptors; lanceolate terminals and simple corpuscles are rapidly adapting receptors.     

The innervation of the primate fungiform papilla--development, distribution and changes following selective ablation

The development of the terminal parts of the chorda tympani nerve, lingual nerve and cranial sympathetics in the macaque fungiform papillae were studied by light- and electron microscopy. Their respective distributions in the intra- and extragemmal compartments of papillae from adult macaques were examined following selective ablation of each nerve. Prior to midgestation, a single bundle of unmyelinated axons which contained numerous axoaxonic synapses passed through the subepithelial connective tissue and ramified in the single nascent chemosensory corpuscle and surrounding non-gustatory epithelium. Following midgestation, additional chemosensory corpuscles appeared, possibly by division of existing corpuscles, myelination of axons was begun, axoaxonic synapses were eliminated, and nerve terminals appeared in the subepithelial connective tissue as free nerve endings and coiled simple nerve endings. In the perinatal period, coiled simple endings, corpuscular receptors and Meissner corpuscles were present in the papilla core. Large numbers of intra-epithelial nerve endings were present in the extragemmal epithelium throughout development. Tonofilament collars ensheathed intra-epithelial axons and 80-100 nm dense core granules, occupying adjacent epithelial cells, appeared to be sequestered near such axons. Experimental selective ablation indicated that the terminal parts of chorda tympani fibers were present only within chemosensory corpuscles. In contrast, lingual nerve endings were present both in the extragemmal epithelium and chemosensory corpuscles and also were the sole supply of corpuscular receptors. Sympathetics appeared to be sparsely distributed in the papilla core. Intra-epithelial axons degenerated within 24 h following transection, while axons with Schwann or lamellar cell sheaths or myelin persisted for at least 3 days.     

The early embryogenesis of papillary (sweat duct) ridges in primate glabrous skin: the dermatotopic map of cutaneous mechanoreceptors and dermatoglyphics

The present study documents the early innervation of the epidermis prior to the onset of differentiation of the papillary (sweat duct) ridge in glabrous digital skin of rhesus monkey embryos measuring 45, 50 and 55 mm (crown-rump) length. We observed small papillary ridges, spaced at a distance of approximately 40 microns, projecting into the dermis in the center of the distal glabrous digital pad of digits 2-5 in the 55-mm embryo. The other digital pads lacked any sign of ridge formation. A two-dimensional, approximately hexagonal grid of afferent nerves was present in the superficial dermis of all digital and palmar pads. At regular intervals of approximately 40 microns, afferent nerves ascended from the superficial dermal nerve plexus and innervated the overlying epidermis. By electron microscopy, axonal growth cones were identified contacting Merkel cells that projected several microns down into the superficial dermis in the digital pad of digit 3. Thus, the earliest wave of differentiated dorsal root ganglion neuroblasts innervates Merkel cells. Schwann cells partially encircled these growing axon tips and could be identified by the presence of rough endoplasmic reticulum and free ribosomes. The youngest embryo studied had no sign of ridge formation; however, axons ascended from the superficial dermal nerve net at 30-40-microns intervals to innervate the epidermis. We conclude that afferent nerve fibers provide a two-dimensional grid that could modulate the spacing and arrangement of the papillary or sweat duct ridges of successive digits. Such an interaction is possible between digits based on the overlapping dermatotopic maps of each rete ridge. An abnormal fingerprint could thus reflect abnormal dorsal root ganglion neuroblasts expressed through mesenchyme and epidermis.     

Comprehensive immunofluorescence and lectin binding analysis of intervibrissal fur innervation in the mystacial pad of the rat

The innervation of the intervibrissal fur in the mystacial pad of the rat and mouse was examined by immunofluorescence with a wide variety of antibodies for neuronal related structural proteins, enzymes, and peptides as well as for lectin binding histofluorescence with Griffonia simplicifolia (GSA). Anti-protein gene product 9.5 (PGP) immunofluorescence labeled all sets of axons and endings. The innervation in the upper dermis and epidermis was distributed through a four tiered dermal plexus. From deep to superficial, the second tier was the source of all apparent myelinated mechanorceptors, the third tier of nearly all the peptidergic and GSA binding innervation, and the fourth tier of nonpeptidergic GSA negative innervation (peptide-/GSA-). Three types of mechanoreceptors—Merkel, transverse lanceolate, and longitudinal lanceolate endings—innervated guard hair follicles. All had similar labeling characteristics for 160 kDa and 200 kDa neurofilament subunits, peripherin, carbonic anhydrase, synaptophysin, and S100. Palisades of longitudinal lanceolate endings were part of piloneural complexes along circumferentially oriented sets of transverse lanceolate endings, peptidergic free nerve endings (FNEs), and peptide-/GSA- FNEs. The longitudinal lanceolate endings were the only mechanoreceptors in the mystacial pad that had detectable calcitonin gene-related peptide. The epidermis contained four types of unmyelinated endings: simple free nerve endings (FNEs), penicillate endings, cluster endings and bush endings. Only the simple FNEs were clearly peptidergic. Virtually all others were peptide-/GSA-. Each bush ending was actually an intermingled cluster of endings formed by several unmyelinated axons and occasionally an Aδ axon. In contrast to the other unmyelinated innervation to the epidermis, bush endings labeled with an antibody against the Schwann cell protein S100. The necks and mouths of follicles, as well as superficial vasculature, were innervated by a mixture of unmyelinated peptidergic and/or GSA labeled sensory and sympathetic axons. Small presumptive sweat glands were innervated by three sets of peptidergic axons of which one was immunoreactive for somatostatin. Potential functions of the various sets of innervation are discussed. J. Comp. Neurol. 385:185–206, 1997. © 1997 Wiley-Liss, Inc.     

Labeling of cutaneous sensory nerve endings with axonally transported horseradish peroxidase and wheat germ agglutinin-horseradish peroxidase conjugate: a methodological study in the rat

Practical aspects on the use of horseradish peroxidase (HRP) and wheat germ agglutinin-horseradish peroxidase conjugate (WGA-HRP) to trace peripheral cutaneous nerve endings have been studied. The parameters studied included application site of the tracer, post-application survival time, tracer concentration and tracer volume. These parameters were examined in the glabrous skin of the rat hindpaw. The best results were obtained with injections of 1 microliter WGA-HRP (20 micrograms/microliter) in dorsal root ganglia innervating the examined cutaneous region and a postinjection survival time of 18-36 h. With this approach extensive and heavy labeling was achieved of epidermal nerve endings, nerve endings in Merkel cell-neurite complexes and Meissner corpuscles. Useful, but less extensive labeling of these types of peripheral nerve endings, was obtained with injections of HRP in the lumbar spinal cord dorsal horn.     

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)     

Degeneration and regeneration of peripheral nerve in the rat trigeminal system. I. Identification and characterization of the multiple afferent innervation of the mystacial vibrissae

Light and electron microscopic techniques were utilized to examine the sensory innervation of the rat mystacial vibrissa. Each vibrissa is innervated by a large nerve bundle that enters the hair below the level of the Ringwulst and a smaller bundle (conus nerve) that pierces the capsule at the top of the hair. The main nerve bundle innervates four types of sensory receptors: (1) free nerve endings (FNEs), (2) lanceolate receptors in the connective tissue below the Ringwulst, (3) Merkel cell-neurite complexes in the outer root sheath, and (4) lanceolate receptors in the intermediary zone. The smaller nerve bundle innervates the area of the sinus hair referred to as the conical body and supplies (1) a Ruffini corpuscle, (2) FNEs, and (3) lanceolate receptors in the inner conical body. The Ruffini complex of the inner conical body and the FNEs of the dense connective tissue below the Ringwulst have not been identified in previous morphological studies of the rat sinus hair. The Ruffini corpuscle, characterized by the compartmentalization of collagen bundles by Schwann cells and fibroblasts (septal cells), encircles the hair shaft in a manner analogous to the Ruffini complexes of nonsinus hairs. Identification of this receptor in the rat vibrissa provides an anatomic explanation for physiological recordings of mystacial primary afferents with slowly adapting type II properties in the rat.     

Distribution and fine structure of calcitonin gene-related peptide-like immunoreactive nerve fibers in the rat skin

Distribution of calcitonin gene-related peptide-like immunoreactive (CGRPI) nerve fibers and their fine structure were examined in the skin of rat foot pads using immunocytochemistry. The CGRPI fibers formed bundles in the dermis and subcutaneous tissue. Two types of single-stranded CGRPI fibers were seen to leave the fiber bundles: one was located along the blood vessels or around the eccrine sweat glands, while the other entered the epidermis directly or through the Meissner's corpuscles in the dermal papillae. CGRPI fibers in the epidermis were distributed widely and were occasionally associated with Merkel cells. Immunoelectron microscopic study revealed that CGRPI fibers located around blood vessels, sweat glands, epidermal keratinocytes and Merkel cells, or in the Meissner's corpuscles did not form typical synaptic contacts with underlying cells, despite being varicose and filled with vesicles resembling synaptic ones. These findings suggested that the CGRP is released non-synaptically from these terminals to influence diffusely the organs surrounding the terminals. These cutaneous fibers seemed to originate from CGRPI neurons (both small type B cells and large type A cells) in the dorsal root ganglia (DRG), because injection of fast blue dye into the cutaneous nerve resulted in labeling of these CGRPI cells in the DRG and excision of the L3-L6 DRG resulted in the non-detection of cutaneous CGRPI fibers in the foot pads. Analysis of the composition of CGRPI fibers found in the rat skin has revealed that these are mostly unmyelinated. C-type fibers with some of them being thin myelinated fibers. This was true even of CGRPI fibers at the proximal end of peripheral neurites of the DRG.(ABSTRACT TRUNCATED AT 250 WORDS)     

Calbindin D-28k- and substance P-immunoreactive primary sensory neurons: Peripheral projections in chick hindlimbs

The peripheral projections of two distinct subpopulations of primary sensory neurons, expressing either calbindin D-28k or substance P, were studied in chick hindlimbs by immunodetecting calbindin D-28k with a rabbit antiserum and substance P with a mouse monoclonal antibody. Calbindin D-28k-immunoreactive axons provided an innervation restricted to specific mechanoreceptors such as muscle spindles, Herbst and Merkel corpuscles, or collars of feather follicles but were absent from Golgi tendon organs. In contrast, substance P-positive axons spread out diffusely in muscles and skin, formed loose plexuses, and extended free branches to the endomysium, arteries, superficial dermis, or dermal pulp of feather follicles. The present results show that calbindin D-28k- and substance P-immunoreactive primary sensory neurons provide distinct modes of innervation to selective targets in peripheral tissues. The results suggest a possible correlation between CaBP-expressing nerve endings and rapidly adapting mechanoreceptors. © 1993 Wiley-Liss, Inc.     

Differential hypertrophy and atrophy among all types of cutaneous innervation in the glabrous skin of the monkey hand during aging and naturally occurring type 2 diabetes

Diabetic neuropathy (DN) is a common severe complication of type 2 diabetes. The symptoms of chronic pain, tingling, and numbness are generally attributed to small fiber dysfunction. However, little is known about the pathology among innervation to distal extremities, where symptoms start earliest and are most severe, and where the innervation density is the highest and includes a wide variety of large fiber sensory endings. Our study assessed the immunochemistry, morphology, and density of the nonvascular innervation in glabrous skin from the hands of aged nondiabetic rhesus monkeys and from age-matched monkeys that had different durations of spontaneously occurring type 2 diabetes. Age-related reductions occurred among all types of innervation, with epidermal C-fiber endings preferentially diminishing earlier than presumptive Adelta-fiber endings. In diabetic monkeys epidermal innervation density diminished faster, became more unevenly distributed, and lost immunodetectable expression of calcitonin gene-related peptide and capsaicin receptors, TrpV1. Pacinian corpuscles also deteriorated. However, during the first few years of hyperglycemia, a surprising hypertrophy occurred among terminal arbors of remaining epidermal endings. Hypertrophy also occurred among Meissner corpuscles and Merkel endings supplied by Abeta fibers. After longer-term hyperglycemia, Meissner corpuscle hypertrophy declined but the number of corpuscles remained higher than in age-matched nondiabetics. However, the diabetic Meissner corpuscles had an abnormal structure and immunochemistry. In contrast, the expanded Merkel innervation was reduced to age-matched nondiabetic levels. These results indicate that transient phases of substantial innervation remodeling occur during the progression of diabetes, with differential increases and decreases occurring among the varieties of innervation.     

Innervation of Putative Rapidly Adapting Mechanoreceptors by Calbindin- and Calretinin-immunoreactive Primary Sensory Neurons in the Rat

Calbindin and calretinin are two homologous calcium-binding proteins that are expressed by subpopulations of primary sensory neurons. In the present work, we have studied the distribution of the neurons expressing calbindin and calretinin in dorsal root ganglia of the rat and their peripheral projections. Calbindin and calretinin immunoreactivities were expressed by subpopulations of large- and small-sized primary sensory neurons and colocalized in a majority of large-sized ones. The axons emerging from calbindin- or calretinin-immunoreactive neurons innervated muscle spindles, Pacini corpuscles and subepidermal lamellar corpuscles in the glabrous skin, formed palisades of lanceolate endings around hairs and vibrissae, and gave rise to intraepidermal nerve endings in the digital skin. Since most of these afferents are considered as rapidly adapting mechanoreceptors, it is concluded that calbindin- or calretinin-expressing neurons innervate particular mechanoreceptors that display physiological characteristics of rapid adaptation to stimuli.     

Developmental dependency of Meissner corpuscles on trkB but not trkA or trkC

The distribution of S100-immunoreactive (ir) corpuscular endings was examined in the palate of wildtype and knockout mice for trkA, trkB or trkC. In wildtype mice, S100-ir corpuscular endings were abundant at the top of palatal rugae. The endings contained 2-4 parallel arrays of S100-ir neurites. The distribution of S100-ir nerve endings in trkA and trkC knockout mice was similar to that in wildtype mice; S100-ir corpuscular endings were abundant in palates of the mutant mice. In trkB knockout mice, the palate was devoid of corpuscular endings, An immunoelectron microscopic method indicated that S100-ir corpuscular endings were identical to Meissner corpuscles. The normal development of Meissner corpuscles is probably dependent on trkB but not trkA or trkC.     

Thalamic connections of two functional subdivisions of the somatosensory forepaw cerebral cortex of the raccoon

The purpose of this study was to compare the thalamic interconnectivities of 2 functionally distinct subdivisions of the somatosensory (Sml) forepaw cortex of the raccoon--the somatotopic subdivision representing the glabrous skin of the digits and the more heterogeneous subdivision representing the hairy skin and claws. Injections of HRP were made into one or the other functional subdivision of a specific digit subgyrus of Sml cortex in 10 adult raccoons. The distribution of HRP-labeled neurons and axon terminals in the thalamus revealed that the 2 sectors have different patterns of thalamic projections. The glabrous skin region of each cortical digit zone was interconnected with a specific crescent-shaped lamella of neurons that extended rostrocaudally through the ventral posterior lateral (VPL) nucleus and typically was separated from adjacent lamellae by small bundles of myelinated fibers. The VPL lamellae constituted relatively distinct digit subnuclei that were connected somatotopically with the glabrous subdivisions of the corresponding cortical digit areas. The projections were dense, topographic, and reciprocal; labeled neurons and axon terminals within a particular lamella overlapped considerably and tended to be arranged in clusters. In contrast, the heterogeneous region of each cortical digit zone was reciprocally connected with the somatotopically appropriate VPL digit subnucleus and with adjoining subnuclei as well. The projections were comparatively sparse, less topographic, and more widely distributed than those of the glabrous skin sectors; groups of HRP-positive neurons and terminals in VPL tended to straddle the borders of the appropriate lamella and extended into adjacent lamellae. Furthermore, small clusters of labeling were found in the dorsal, presumed kinesthetic region of VPL and in portions of the ventral posterior inferior nucleus and the posterior nucleus. These results indicate that the glabrous cortical subdivisions have precise, somatotopically organized connections with specific VPL subnuclei, whereas the heterogeneous cortical subdivisions have more diffuse and scattered connections with several subregions of VPL and other thalamic nuclei as well. These 2 thalamocortical projection patterns may account for many of the differing functional properties of neurons residing within the 2 cortical sectors. Finally, the convergent thalamic projections to the heterogeneous cortical regions could contribute, at least indirectly, to the functional reactivation that occurs within Sml cortex of the raccoon following peripheral nerve transection (Kelahan and Doetsch, 1984).