Bryce L. Munger

The neuroanatomical basis for the protopathic sensibility of the human glans penis.

The human glans penis is covered by stratified squamous epithelium and a dense layer of connective tissue equivalent to the dermis of typical skin. Rete ridges of the epidermis are irregular and vary in height depending on location, age, and presence or absence of a foreskin. The papillary layer of the dermis blends into and is continuous with the dense connective tissue forming the tunica albuginea of the corpus spongiosum of the glans penis. The most numerous nerve terminals are free nerve endings (FNEs) present in almost every dermal papilla, as well as scattered throughout the deeper dermis. FNEs are characterized by an incomplete Schwann cell investment, and contain irregularly scattered neurofilaments and neurotubules, clusters of mitochondria, vesicles of variable size and various inclusions. The ratio of FNEs to corpuscular receptors is approximately 10:1 and a similar ratio of small to large axons is seen in dermal nerves. Genital end bulbs are present throughout the glans, but are most numerous in the corona and near the frenulum. The unique corpuscular receptor of the glans penis consists of axon terminals that at an ultrastructural level resemble a tangled skein of FNEs. Simple, Pacinian and Ruffini corpuscles were occasionally identified predominantly in the corona glandis. Epidermal Merkel nerve endings and other types of mechanoreceptors typically found in primate glabrous skin (lip or digit) are not present. Rarely, dermal Merkel cells have been identified associated with genital end bulbs. The abundance of FNEs in isolated as well as corpuscular form can be correlated with the embryogenesis and known neurophysiologic and psychophysical parameters of sensory function of the glans penis. Finally, the divergence in reported values for the threshold of tactile and painful stimuli when applied to glabrous skin of fingertip and glans penis can be considered as an example of dissociated sensibility. The anatomical basis for this dissociation is the abundance of FNEs and absence of Merkel terminals and typical Meissner corpuscles in the covering of the glans, and the converse in glabrous skin of the digit.

The pilo-ruffini complex: A non-sinus hair and associated slowly-adapting mechanoreceptor in primate facial skin

A spray-type of nerve ending identified as a Ruffini corpuscle closely associated with a non-sinus hair has been defined in terms of its histologic, ultrastructural and physiologic parameters. The hair and its associated mechanoreceptor, termed a pilo-Ruffini complex, responds as a slowly adapting (SA) mechanoreceptor, whereas most non-sinus hair-associated mechanoreceptors are rapidly adapting. Morphologically, the terminal nerve fibers branch repeatedly within a unique connective tissue matrix, and the neurite and associated connective tissue matrix forms a collar around the hair follicle. This receptor, on the basis of its organization, is interpreted as corresponding to the corpuscle or end organ of Ruffini.

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 nerves 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.

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

Abstract 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 (FNEs) 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. FNEs 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.

The Merkel rete papilla — a slowly adapting sensory receptor in mammalian glabrous skin

Abstract The present study has identified the anatomical receptor characterized physiologically as a slowly adapting mechanoreceptor. The receptor has been named a Merkel rete papilla (M-r papilla). An M-r papilla consists of a group of Merkel cells, associated neurites and epidermal cells projecting from the lower portion of a rete ridge into the dermis. Three to six individual nerve fibers enter a papilla and repeatedly divide. Fine terminal branches become associated with Merkel cells in a manner similar to other Merkel cell-neurite complexes described previously. The Merkel cell-neurite complexes in the M-r papillae are the anatomical substrate for the slowly adapting receptors present in raccoon glabrous palmar skin.

Functional properties of mechanoreceptors in glabrous skin of the raccoon's forepaw.

Abstract Utilizing a mechanical stimulator which permits precise control over the velocity and extent of skin displacement, response properties of 76 single myelinated median nerve fibers innervating mechanoreceptors in raccoon glabrous forepaw skin were examined. All units fell into one of two categories, rapidly adapting (34 units), responding only during skin movement, and slowly adapting (42 units), responding during both moving and static phases of skin displacement. Both types had single receptive fields, 85% of which were less than 1 mm 2 in diameter, and low thresholds to mechanical displacement. Frequency of discharge during the moving phase of stimulation was a power function of velocity for both types, but discharge patterns varied. Power function slope constants were greater for the rapidly adapting units, but the slowly adapting units exhibited a higher maximum discharge rate. Results are discussed with particular reference to the possible roles of these receptors in tactile exploratory behavior.

Fetal development of primate chemosensory corpuscles. II: Synaptic relationships in early gestation

Fetal macaque chemosensory corpuscles during the last part of gestation contained chemosensory, sustentacular, and undifferentiated basal cells. Sustentacular cells had apical secretory granules and no specialized contacts with axons. Chemosensory cells contained basal collections of 80–100 nm dense core granules, and specialized axonal contacts of three types—afferent synapses, efferent synapses, and subsurface cisternae. Afferent synapses were commonly present on electron opaque cells with many 80–100‐nm granules, typical 40–60‐nm synaptic vesicles, and a few cisternae of smooth or granular endoplasmic reticulum. Cells with subsurface cisternae and/or efferent synapses were usually electron lucent, lacked vesicles and granules, and contained numerous intracytoplasmic cisternal elements. A continuum of intermediate forms was observed. It is postulated that transition of synaptic arrays accompanies the maturation of individual chemosensory cells.

The Sensorineural Organization of the Digital Skin of the Raccoon (Part 1 of 2)

In a study of first-order mechanoreceptive afferent fibers innervating the raccoons glabrous forepaw skin, two types of units, rapidly and slowly adapting (RA and SA), were distinguished, both belonging to the group II class. General characteristics of the two types have been described, as well as the nature of their response to precisely controlled mechanical stimuli. Average rate of responding of both to mechanical stimuli having constant velocity is a power function of velocity. Vibratory tuning points were in the range of 7–10 Hz for the SA and 20–100 Hz for the RA. The M-r papillae are slowly adapting and exquisitely sensitive mechanoreceptors sitting at the base of each digital rete ridge. The rete ridge is, in turn, mechanically coupled to the grossly observable epidermal domes on the skin surface. Local amplification is evident from the multiple neurites innervating each M-r papilla. Overlapping receptive fields are absent anatomically and physiologically. The discrete and small (<1 mm in diameter) receptive fields permit anatomical localization of the receptor.Information on transient deformation is coded by the dermal simple corpuscles which are rapidly adapting. These also exhibit discrete, small, nonoverlapping receptive fields permitting anatomical localization of the receptor. Their anatomical variability deserves further study.

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.

Multiple afferent innervation of primate facial hairs — Henry Head and Max Von Frey revisited

Large guard hairs as well as small vellus hairs are multiple innervated having lanceolate terminals of variable number. Ruffini corpuscles consisting of fine axonal ramifications are arranged circularly and located external to the lanceolate terminals. Free nerve endings (FNEs) can also be identified on some hairs distinct from Ruffini terminals. Ruffini terminals and FNEs are usually innervated by axons from the superficial dermal nerve net whereas lanceolate terminals are innervated by axons from the deeper portions of the dermal nerve net. All guard hairs have both types of terminals (lanceolate and Ruffini) confirming Hoggan and Hoggan, Retzius and Symonowicz, and most guard hairs have presumptive FNEs. Many vellus hairs have only small Ruffini endings or FNEs. The diameter of axons supplying Ruffini terminals is 1-2 micrometer and those to lanceolate terminals is 2-4 micrometers. Axons innervating lanceolate and Ruffini terminals branch rarely as correlated with small punctate receptive fields. FNEs branch widely and are correlated with large receptive fields of known nociceptors. The multiplicity of anatomically defined terminals is consistent with the known diversity of physiologically defined hair mechanoreceptive afferents as well as perceptual complexity of human hairy skin. The concept of multiple innervation of hairs confirms Heads prediction and could provide the anatomical basis of Heads basic thesis of altered sensibilities in nerve regeneration (i.e. epicritic and protopathic responses). Heads concept of two separate nervous systems, however, is an over-simplification in the light of current knowledge.