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.     

Sequential differentiation of sensory innervation in the mystacial pad of the ferret

The mystacial pad of the ferret has an elaborate sensory innervation provided by three types of terminal nerves that arise from the infrorbital branch of the trigeminal nerve. Deep and superficial vibrissal nerves innervate nearly exclusive targets in the large follicle–sinus complexes (F-SCs) at the base of each tactile vibrissa. Dermal plexus nerves innervate the fur between the vibrissae. Each type of nerve provides a similar variety of sensory endings, albeit to different targets. In this study, Winkelmann and Sevier-Munger reduced silver techniques revealed that most of the endings differntiate postnatally in an overlapping sequence like that observed previously in the rat. Afferents from the deep vibrissal nerves begin to differentiate first, followed successively by those from superficial vibrissal nerves and the dermal plexus. Within each type of nerve, Merkel endings begin to differentiate first, followed successively by lanceolate endings and circumferential endings. In the ferret, the differentiation of the intervibrissal fur and its innervation is slightly delayed but substantially overlaps the development of the vibrissal innervation, whereas in the rat it occurs almost entirely later. There was no evidence of a transient exuberant or misplaced innervation or other secondary remodeling. Differentiating afferents and endings are located only in the sites normally seen in the adult, suggesting a high degree of afferent-target specificity. In the ferret, innervation is virtually lacking in one target—the inner conical body of the F-SCs, which is densely innervated in the rat. This lack was due to a failure of innervation to develop rather than to a secondary elimination of a transient innervation. © 1993 Wiley-Liss, Inc.     

Successive waves of differentiation of cutaneous afferents in rat mystacial skin

The present study has traced the sequence of maturation of sensory receptors in the mystacial pad of postnatal rats. At birth the follicle-sinus complexes (F-SC) are well innervated by deep vibrissal nerves although the number of axons entering the sinus is less than that in the adult. The innervation of the F-SC by the conus or superficial vibrissal nerves derived from skin nerves that form the superficial dermal nerve plexus is limited to the Merkel rete ridge collar at birth, and the innervation to the inner conical body is conspicuously absent. The inner conical body innervation begins to appear 3-4 days after birth and rapidly matures over the week. By 3 weeks of age the F-SCs have a mature sensory innervation. At birth small guard hairs are present in the intervibrissal pelage and are associated with scant axons of the superficial dermal nerve plexus, but no mature sensory terminals are present. The sensory innervation of the intervening pelage begins to differentiate during the second week and mature piloneural complexes can be recognized by 3 weeks of age. Innervation to vellus hairs is still developing at 3-4 weeks of age. These maturational changes in peripheral sensory innervation correlate with gradual changes in the structure of barrels in the first somatosensory cortex (SI). Sequential waves of differentiation of sensory receptors appear to be a general feature of neural 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)     

Similarities and differences in the innervation of mystacial vibrissal follicle-sinus complexes in the rat and cat: a confocal microscopic study

Our confocal three-dimensional analyses revealed substantial differences in the innervation to vibrissal follicle-sinus complexes (FSCs) in the rat and cat. This is the first study using anti-protein gene product 9.5 (PGP9.5) immunolabeling and confocal microscopy on thick sections to examine systematically the terminal arborizations of the various FSC endings and to compare them between two species, the rat and the cat, that have similar-appearing FSCs but different exploratory behaviors, such as existence or absence of whisking. At least eight distinct endings were clearly discriminated three dimensionally in this study: 1) Merkel endings at the rete ridge collar, 2) circumferentially oriented lanceolate endings, 3) Merkel endings at the level of the ring sinus, 4) longitudinally oriented lanceolate endings, 5) club-like ringwulst endings, 6) reticular endings, 7) spiny endings, and 8) encapsulated endings. Of particular contrast, each nerve fiber that innervates Merkel cells at the level of the ring sinus in the rat usually terminates as a single, relatively small cluster of endings, whereas in the cat they terminate en passant as several large clusters of endings. Also, individual arbors of reticular endings in the rat ramify parallel to the vibrissae and distribute over wide, overlapping territories, whereas those in the cat ramify perpendicular and terminate in tightly circumscribed territories. Otherwise, the inner conical body of rat FSCs contains en passant, circumferentially oriented lanceolate endings that are lacking in the cat, whereas the cavernous sinus of the cat has en passant corpuscular endings that are lacking in the rat. Surprisingly, the one type of innervation that is the most similar in both species is a major set of simple, club-like endings, located at the attachment of the ringwulst, that had not previously been recognized as a morphologically unique type of innervation. Although the basic structure of the FSCs is similar in the rat and cat, the numerous differences in innervation suggest that these species would have different tactile capabilities and perceptions possibly related to their different vibrissa-related exploratory behaviors.     

Adaptations in the structure and innervation of follicle-sinus complexes to an aquatic environment as seen in the Florida manatee (Trichechus manatus latirostris)

Florida manatees are large-bodied aquatic herbivores that use large tactile vibrissae for several purposes. Facial vibrissae are used to forage in a turbid water environment, and the largest perioral vibrissae can also grasp and manipulate objects. Other vibrissae distributed over the entire postfacial body appear to function as a lateral line system. All manatee vibrissae emanate from densely innervated follicle-sinus complexes (FSCs) like those in other mammals, although proportionately larger commensurate with the caliber of the vibrissae. As revealed by immunofluorescence, all manatee FSCs have many types of C, Adelta and Abeta innervation including Merkel, club, and longitudinal lanceolate endings at the level of the ring sinus, but they lack other types such as reticular and spiny endings at the level of the cavernous sinus. As in non-whisking terrestrial species, the inner conical bodies of facial FSCs are well innervated but lack Abeta-fiber terminals. Importantly, manatee FSCs have two unique types of Abeta-fiber endings. First, all of the FSCs have exceptionally large-caliber axons that branch to terminate as novel, gigantic spindle-like endings located at the upper ring sinus. Second, facial FSCs have smaller caliber Abeta fibers that terminate in the trabeculae of the cavernous sinus as an ending that resembles a Golgi tendon organ. In addition, the largest perioral vibrissae, which are used for grasping, have exceptionally well-developed medullary cores that have a structure and dense small-fiber innervation resembling that of tooth pulp. Other features of the epidermis and upper dermis structure and innervation differ from that seen in terrestrial mammals.     

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.     

TrkC kinase expression in distinct subsets of cutaneous trigeminal innervation and nonneuronal cells

Neurotrophin-activated receptor tyrosine kinases (Trks) regulate sensory neuron survival, differentiation, and function. To permanently mark cells that ever express TrkC-kinase, mice with lacZ and GFP reporters of Cre recombinase activity were crossed with mice having IRES-cre inserted into the kinase-containing exon of the TrkC gene. Prenatal reporter expression matched published locations of TrkC-expression. Postnatally, more trigeminal neurons and types of mystacial pad innervation expressed reporter than immunodetectable TrkC, indicating that some innervation transiently expresses TrkC-kinase. Reporter-tagged neurons include all those that immunolabel for TrkC, a majority for TrkB, and a small proportion for TrkA. TrkA neurons expressing TrkC-reporter range from small to large size and supply well-defined types of mystacial pad innervation. Virtually all small neurons and C-fiber innervation requires TrkA to develop, but TrkC-reporter is present in only a small proportion that uniquely innervates piloneural complexes of guard hairs and inner conical bodies of vibrissa follicle-sinus complexes. TrkC-reporter is expressed in nearly all presumptive Adelta innervation, which is all eliminated in TrkA knockouts and partially eliminated in TrkC knockouts. Many types of Abeta-fiber innervation express TrkC-reporter including all Merkel, spiny, and circumferentially oriented lanceolate endings, and some reticular and longitudinally oriented lanceolate endings. Only Merkel endings require TrkC to develop and survive, whereas the other endings require TrkA and/or TrkB. Thus, TrkC is required for the existence of some types of innervation that express TrkC, but may have different functions in others. Many types of nonneuronal cells affiliated with hair follicles and blood vessels also express TrkC-reporter but lack immunodetectable TrkC.     

Sensory innervation in the inner conical body of the vibrissal follicle-sinus complex of the rat

The innervation of the inner conical body of the vibrissal follicle-sinus complex of the rat was examined by high-voltage and conventional transmission electron microscopy of serial and semi-serial sections. The inner conical body is innervated by axons supplied almost exclusively by several superficial vibrissal nerves that arise from the infraorbital branch of the trigeminal nerve and converge upon the neck of the follicle-sinus complex. Each superficial vibrissal nerve contains a few Aδ myelinated axons and several bundles of 20–30 unmyelinated axons. These axons enter the inner conical body and distribute circumferentially within 7–10 ring-like arrays that encircle the vibrissal follicle and are stacked through the superficial-to-deep extent of the inner conical body. Each ring consists of 1 or 2 myelinated axons and several small bundles of 2–15 unmyelinated axons enclosed in sheaves of parallel collagen fibrils. Myelinated axons provide exclusively lanceolate endings that may arise at the termination of the axon or at nodes of Ranvier. Within the small bundles, unmyelinated axons individually terminate in succession as abrupt cytoplasmic swellings referred to as cytoplasmic blebs, which contain mitochondria or clusters of clear or dense-core vesicles. Because of their affiliation with collagen fibrils and the proximity of myelinated axons, the blebbed endings may have been misinterpreted as Ruffini endings in previous studies. Their structure, distribution, and origin from unmyelinated axons suggest that the blebbed endings may constitute a unique array of low-threshold C-mechanoreceptors. © 1993 Wiley-Liss, Inc.     

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.     

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.     

A comparative light microscopic analysis of the sensory innervation of the mystacial pad. II. The common fur between the vibrissae

The innervation to the common fur between the vibrissae was examined in the hamster, mouse, rat, gerbil, rabbit, guinea pig, and cat. Samples were taken from central locations among the more caudal vibrissae in the mystacial pad and processed with Richardson's variant of the Bielschowsky silver technique or with Winkelmann's silver technique to selectively stain peripheral axons and terminals. Additional samples were taken among the rostral vibrissae in the rat. We found major unpredictable species-related variations in the distribution of receptor types, innervation density, and the quantity of innervation in the skin between neighboring vibrissae. The common fur is composed of numerous larger guard hairs and even more numerous smaller vellus hairs. The guard hairs usually are richly innervated with fully developed piloneural complexes composed primarily of a pallisade of lanceolate endings and a circumferential array of Ruffini and free nerve endings. The vellus hairs are usually innervated by individual or shared free nerve endings. The piloneural complexes in the cat, rat, and mouse are usually complete, whereas those in the other species were usually incomplete and lacked Ruffini endings. There is considerable interspecies variation in the relative quantity of innervation between homologous neighboring vibrissae. The quantity of innervation is related to a combination of receptor completeness, innervation density, and distance between vibrissae. The quantity of intervibrissal fur innervation is by far highest in the cat, relatively high in the rabbit, relatively low in the hamster and caudal mystacial pad of the rat, and lowest in the mouse, gerbil, guinea pig, and rostral mystacial pad of the rat. The differences in the innervation between the cat and the rabbit correlate well with published physiologic data on types of receptor units. Also, barrels are most prominent in species having relatively low quantities of intervibrissal innervation and are less prominent or absent in species having high quantities of intervibrissal innervation.     

Abnormal sensory and motor reinnervation of rat muscle spindles following nerve transection and suture

Summary Muscle spindles from the lower lumbrical muscles of rats were studied by transmission and scanning electron microscopy following reinnervation (i) after a single sciatic nerve crush lesion and (ii) after transection and immediate epineurial suture of the sciatic nerve. In all muscle spindles, regenerated sensory or motor nerve endings were encountered 3 months after making the lesions although in the nerve-transection group, regenerated nerve endings were seen less frequently before 6 months of recovery. Abnormalities in reinnervated spindles following neurotomy comprised: (1) multiplicity of axonal sprouts (hyperinnervation), sometimes irregularly related to, although never in direct contact with, regenerated sensory nerve endings; (2) altered contact relationships between sensory nerve endings and intrafusal muscle fibers; (3) abnormal structure of nerve endings; and (4) irregular association of Schwann cell processes to regenerated sensory nerve endings. These findings indicate that reinnervation of muscle spindles following transection and suture of a peripheral nerve, i.e., after complete interruption of its continuity, in fact, occurs although the fine structural abnormalities observed are supposed to interfere with adequate functional restoration.Supported by a grant from the Deutsche Forschungsgemeinschaft: Di 386/1-1     

Directional specificity of regenerating primary sensory neurons after peripheral nerve crush or transection and epineurial suture A sequential double-labeling study in the rat

Clinical and experimental observations have demonstrated that peripheral nerve transection generally results in lasting disturbed sensory discrimination whereas nerve crush is followed by more or less complete functional restoration. This has been explained by an increased misdirection of regenerating fibers after transection as compared to crush injury. In the present study, sequential double-labeling was used to investigate the relative proportions of peripherally misdirected sensory fibers in the sural and tibial nerve branches after crush or transection of the parent sciatic nerve in the rat. Control experiments showed that 0.21% ± 0.12 (mean ± S.D.) of all labeled tibial and sural neurons normally send axons to both nerves. After sciatic nerve crush or transection, 1.31% ± 0.78 and 3.79% ± 3.01, respectively, of all labeled tibial and sural axons were double-labeled indicating previously sural axons now having an axon in the tibial. Statistically significant differences in the percentages of bidirectional sciatic sensory neurons were found between the normal controls and after crush injury (P < 0.01) or transection injury (P < 0.001), respectively, but not between transection and crush (P > 0.05). The results indicate that the number of sensory neurons having an axon in two peripheral nerves is normally very small, that a substantial number of sensory axons become misdirected after both crush and transection with resuture, and that the number of misdirected fibers in the major sciatic branches after these types of injury is similar.     

Anatomical consequences of neonatal infraorbital nerve transection upon the trigeminal ganglion and vibrissa follicle nerves in the adult rat

A large body of experimental literature has demonstrated that neonatal infraorbital nerve damage in rodents produces anatomical and/or functional alterations of the normal whisker representation in central trigeminal structures. Less is known about the organization of primary afferent components of the trigeminal system following this manipulation. Such information provides an important basis for interpreting the central changes observed following damage of infraorbital nerve fibers at birth. We have therefore examined the composition and order of peripheral innervation in the pathway from the trigeminal ganglion to the vibrissa follicles in adult rats subjected to unilateral neonatal infraorbital nerve transection. Electron microscopy was used to determine the number and diameter of myelinated and unmyelinated fibers in vibrissa follicle nerves of these animals. Wheat germ agglutinin-horseradish peroxidase and fluorescent retrograde tracers were employed to examine the number and diameter, as well as the topographic organization and branching, of ganglion cells innervating the vibrissae in these rats. The data presented below indicate that neonatal infraorbital nerve transection has the following consequences within the adult trigeminal nerve and ganglion: 1) an alteration of the gross morphology of vibrissal nerves, 2) a significant reduction in the average number (85.4%) and diameter (32.6%) of myelinated, but not unmyelinated, follicle nerve axons, 3) a significant decrease in the average number (36.8%) of trigeminal ganglion cells innervating vibrissa follicles, 4) no significant change in the distribution of ganglion cell diameters, 5) an increase in peripheral branching (1.8-fold) of these ganglion cell axons, and 6) an alteration of somatotopic order within the trigeminal ganglion. Taken together, these data indicate that neonatal infraorbital nerve transection produces a profound reorganization of the primary afferent component of the trigeminal neuraxis.     

Prior collateral sprouting enhances elongation rate of sensory axons regenerating through acellular distal segment of a crushed peripheral nerve

Regenerating axons in crushed peripheral nerves grow through their distal nerve segments even in the absence of Schwann cell support, but their elongation rate is reduced by 30%. We examined whether prior exposure of sensory neurons to trophic factors achieved either by collateral sprouting or regeneration after conditioning lesion could enhance subsequent regeneration of their axons after crush, and compensate for loss of cell support. Collateral sprouting of the peroneal cutaneous sensory axons in the rat was evoked by transection of adjacent peripheral nerves in the hind leg. The segment of the peroneal nerve distal to the crush was made acellular by repeated freezing. Sensory axon elongation rate during regeneration was measured by the nerve pinch test. Prior axonal sprouting for two weeks increased the elongation rate of sensory axons through the acellular distal nerve segment back to normal value observed in control crushed nerves. The number of axons in the acellular distal segment at a fixed distance from the crush site was about 50% greater in sprouting than in control non-sprouting nerves. However, prior sprouting caused no further increase of axon elongation rate in control crushed nerves. Prior collateral sprouting, therefore, could in some respect compensate for loss of cell support in the distal nerve segment after crush lesion. This suggests that loss of cell-produced trophic factors is probably responsible for slower elongation rate through the acellular distal nerve segment. Surprisingly, prior conditioning lesion caused no enhancement of elongation rate of the sensory axons regenerating in the absence of cell support.     

Regeneration of motor axons in the rat sciatic nerve studied by labeling with axonally transported radioactive proteins.

Labeling regenerating axons with axonally transported radioactive proteins provides information about the location of the entire range of axons from the fastest growing ones to those which are trapped in the scar. We have used this technique to study the regeneration of motor axons in the rat sciatic nerve after a crush lesion. From 2 to 14 days after the crush the lumbar spinal cord was exposed by laminectomy and multiple injections of [3H]proline were made stereotactically in the ventral horn. Twenty-four hours later the nerves were removed and the distribution of radioactivity along the nerve was measured by liquid scintillation counting. There was a peak of radioactivity in the regenerating axons distal to the crush due to an accumulation of label in the tips of these axons. After a delay of 3.2 +/- 0.2 (S.E.) days, this peak advanced down the nerve at a rate of 3.0 +/- 0.1 (S.E.) mm/day. The leading edge of this peak, which marks the location of the endings of the most rapidly growing labeled fibers, moved down the nerve at a rate of 4.4 +/- 0.2 mm/day after a delay of 2.1 +/- 0.2 days; this is the same time course as that of the most rapidly regenerating sensory axons in the rat sciatic nerve, measured by the pinch test. Another peak of radioactivity at the crush site, presumed to represent the ends of unregenerated axons or misdirected sprouts, declined rapidly during the first week, and more slowly thereafter.     

Specific and nonspecific regeneration of motor axons after sciatic nerve injury and repair in the rat

The pattern of motor axon regeneration following unilateral sciatic nerve lesions (freezing or transection) was studied in adult rats. Transected nerves were repaired with epineurial or fascicular sutures. Four months after the lesion, the motor neuron cell body localization in the spinal cord of plantar or common peroneal nerve axons were examined bilaterally with retrograde transport of horseradish peroxidase. Motor neuron cell body localization was similar bilaterally after freezing, indicating that regenerating axons had reached their original peripheral innervation territory. However, after nerve transection, irrespective of whether epineurial or fascicular sutures were used, motor neuron cell body distribution on the operated side was abnormal with numerous labeled cell bodies located outside the area of the normal motor neuron pool. This finding indicates that after nerve transection the normal pattern of motor axon innervation is not restored even after fascicular nerve repair.     

Uptake of horseradish peroxidase in sensory nerve terminals of mouse trigeminal nerve

Summary Uptake of horseradish peroxidase (HRP) in sensory nerve terminals in sinus hair in the nose of the mice was studied after local (s.c.) or i.v. injection. HRP spread into the sinus hair follicles and surrounded the nerve terminals of the Merkel disc endings and lanceolate terminals. It was incorporated into vacuoles and vesicles of these terminals. Subsequently, HRP was demonstrated in nerve cell bodies in the ophthalmomaxillary part of the trigeminal ganglion, indicating a somatopetal axonal transport of the tracer. In this way the sensory neurons may be subjected to various influences from the periphery