Dorsal Root Fibers Research Articles

Spinal motor mapping by epidural stimulation of lumbosacral posterior roots in humans.

SummaryEpidural electrical stimulation of the spinal cord is an emergent strategy for the neurological recovery of lower-extremity motor function. Motoneuron pools are thought to be recruited by stimulation of posterior roots. Here, we linked electromyographic data of epidurally evoked lower-extremity responses of 34 individuals with upper motoneuron disorders to a population model of the spinal cord constructed using anatomical parameters of thousands of individuals. We identified a relationship between segmental stimulation sites and activated spinal cord segments, which made spinal motor mapping from epidural space possible despite the complex anatomical interface imposed by the posterior roots. Our statistical approach provided evidence for low-threshold sites of posterior roots and effects of monopolar and bipolar stimulation previously predicted by computer modeling and allowed us to test the impact of different upper motoneuron disorders on the evoked responses. Finally, we revealed a statistical association between intraoperative and postoperative mapping of the spinal cord.

Tactile innervation densities across the whole body.

The skin is our largest sensory organ and innervated by afferent fibers carrying tactile information to the spinal cord and onto the brain. The density with which different classes of tactile afferents innervate the skin is not constant but varies considerably across different body regions. However, precise estimates of innervation density are only available for some body parts, such as the hands, and estimates of the total number of tactile afferent fibers are inconsistent and incomplete. Here we reconcile different estimates and provide plausible ranges and best estimates for the number of different tactile fiber types innervating different regions of the skin, using evidence from dorsal root fiber counts, microneurography, histology, and psychophysics. We estimate that the skin across the whole body of young adults is innervated by ∼230,000 tactile afferent fibers (plausible range: 200,000-270,000), with a subsequent decrement of 5-8% every decade due to aging. Fifteen percent of fibers innervate the palmar skin of both hands and 19% the region surrounding the face and lips. Slowly and fast-adapting fibers are split roughly evenly, but this breakdown varies with skin region. Innervation density correlates well with psychophysical spatial acuity across different body regions, and, additionally, on hairy skin, with hair follicle density. Innervation density is also weakly correlated with the size of the cortical somatotopic representation but cannot fully account for the magnification of the hands and the face.

Prior perineural or neonatal treatment with capsaicin does not alter the development of spinal microgliosis induced by peripheral nerve injury

Peripheral nerve injury is associated with spinal microgliosis which plays a pivotal role in the development of neuropathic pain behavior. Several agents of primary afferent origin causing the microglial reaction have been identified, but the type(s) of primary afferents that release these mediators are still unclear. In this study, specific labeling of C-fiber spinal afferents by lectin histochemistry and selective chemodenervation by capsaicin were applied to identify the type(s) of primary afferents involved in the microglial response. Comparative quantitative morphometric evaluation of the microglial reaction in central projection territories of intact and injured peripheral nerves in the superficial (laminae I and II) and deep (laminae III and IV) spinal dorsal horn revealed a significant, about three-fold increase in microglial density after transection of the sciatic or the saphenous nerve. Prior perineural treatment of these nerves with capsaicin, resulting in a selective defunctionalization of C-fiber afferent fibers failed to affect spinal microgliosis. Similarly, peripheral nerve injury-induced increase in microglial density was unaffected in rats treated neonatally with capsaicin known to result in a near-total loss of C-fiber dorsal root fibers. Perineural treatment with capsaicin per se did not evoke a significant increase in microglial density. These observations indicate that injury-induced spinal microgliosis may be attributed to phenotypic changes in injured myelinated primary afferent neurons, whereas the contribution of C-fiber primary sensory neurons to this neuroimmune response is negligible. Spinal myelinated primary afferents may play a hitherto unrecognized role in regulation of neuroimmune and perisynaptic microenvironments of the spinal dorsal horn.

Morphological study of myelinated and unmyelinated fibres in the sacrococcygeal dorsal roots of the rat.

The number and calibre of myelinated and unmyelinated fibres of the sacrococcygeal dorsal roots innervating the tail of rats were studied by means of light and electron microscopy. There were an estimated total of 12,500 myelinated and 25,500 unmyelinated dorsal root fibres innervating the tail of a rat. The results showed that from the second sacral (S2) to the fourth sacral (S4) segment, the fibre diameter spectrum of myelinated fibres within each dorsal root was bimodal with two peaks at 5 microns and 10 microns, respectively. The first sacral (S1) segment was composed of numerous smaller-size myelinated fibres, thus forming a right-skewed distribution. The coccygeal (Co) segments showed a unimodal distribution peaking at 10 microns for the first (Co1) segment and gradually shifting to 7 microns for the third (Co3) segment. Overall, there was a continuous relative increase of the larger vs. the smaller myelinated fibres from the sacral to coccygeal segments. The fibre diameter of unmyelinated fibres of all these roots was unimodal with a single peak at 0.5 microns. The ratio of unmy- elinated to myelinated fibre numbers was on average 2.83 for the S1-S2 roots, 1.66 for the S3-S4 roots, and 1.24 for the coccygeal roots. The comparison of the left- and right-side nerve fibres show that there was no significant difference, thus implying a symmetrical sensory innervation of the rat's tail.

Computational Study of the Effect of Electrode Polarity on Neural Activation Related to Paresthesia Coverage in Spinal Cord Stimulation Therapy

Using computer simulation, we investigated the effect of electrode polarity on neural activation in spinal cord stimulation and propose a new strategy to maximize the activating area in the dorsal column (DC) and, thus, paresthesia coverage in clinical practice. A new three-dimensional spinal cord model at the T10 vertebral level was developed to simulate neural activation induced by the electric field distribution produced by different typical four-contact electrode polarities in single- and dual-lead stimulation. Our approach consisted of the combination of a finite element model of the spinal cord developed in COMSOL Multiphysics and a nerve fiber model implemented in MATLAB. Five evaluation parameters were evaluated, namely, the recruitment ratio, the perception and discomfort thresholds, and the activating area and depth. The results were compared quantitatively. The dual-guarded cathode presents the maximum activating area and depth in single- and dual-lead stimulation. However, the lowest value of the ratio between the perception threshold in DC and the perception threshold in the dorsal root (DR) is achieved when the guarded cathode is programmed. Although the two versions of bipolar polarity (namely bipolar 1 and bipolar 2) produce higher activating area and depth than the guarded cathode, they are suitable for producing DR stimulation. Similarly, dual-lead stimulation is likely to activate DR fibers because the electrodes are closer to these fibers. The results suggest that the activating area in the DC is maximized by using the dual-guarded cathode both in single- and dual-lead stimulation modes. However, DC nerve fibers are preferentially stimulated when the guarded cathode is used. According to these results, the new electrode programming strategy that we propose for clinical practice first uses the dual-guarded cathode, but, if the DR nerve fibers are activated, it then uses guarded cathode polarity.

Efferent projections of dorsal root afferents in the spinal cord of the lamprey Lampetra fluviatilis

Arborization of dorsal root afferents was studied in the lamprey spinal cord by the method of horseradish peroxidase transport. Direct evidence was obtained for the presence of efferent fibers in dorsal roots, representing collaterals that depart from ascending and descending intraspinal branches of sensory axons and travel towards the periphery through the adjacent roots.

Transplantation of Cultured Olfactory Bulb Cells Prevents Abnormal Sensory Responses during Recovery from Dorsal Root Avulsion in the Rat

The central branches of the C7 and C8 dorsal roots were avulsed close to their entry point into the spinal cord in adult rats. The forepaw responses to heat and cold stimuli were tested at 1, 2, and 3 weeks after injury. Over this period, the paws were sensitive to both stimuli at 1-2 weeks and returned toward normal at 3 weeks. Immunohistology showed no evidence of axonal regeneration into the spinal cord in a control group of rats with avulsion only, implying that adjacent dorsal roots and their corresponding dermatomes were involved in the recovery. In a further group of rats, a mixture of bulbar olfactory ensheathing cells and olfactory nerve fibroblasts were transplanted into the gap between the avulsed roots and the spinal cord at the time of avulsion. These rats showed no evidence of either loss of sensation or exaggerated responses to stimuli at any of the time points from 1 to 3 weeks. Immunohistology showed that the transplanted cells formed a complete bridge, and the central branches of the dorsal root fibers had regenerated into the dorsal horn of the spinal cord. These regenerating axons, including Tuj1 and CGRP immunoreactive fibers, were ensheathed by the olfactory ensheathing cells. This confirms our previous demonstration of central regeneration by these transplants and suggests that such transplants may provide a useful means to prevent the development of abnormal sensations such as allodynia after spinal root lesions.

AB299. SPR-26 Micturition and defecation behavior following pelvic decentralization in a canine model

ObjectiveWe demonstrated motor reinnervation of the decentralized canine urinary bladder by increased detrusor pressure induced by electrical stimulation of the transferred genitofemoral or femoral nerves in 21 of 28 animals. We previously reported evidence of bladder and bowel fullness sensation in these new neuronal pathways based on observation of micturition and defecation postures in the reinnervated animals. Our focus here was to determine whether these postures are eliminated in decentralized animals.MethodsThe pelvis was decentralized by bilateral transection of the hypogastric nerves and all spinal nerve roots caudal to L7 in 6 female canines. A separate group of 6 female canines was decentralized identically with the additional bilateral transection of L7 dorsal roots. Video surveillance of the housing cages allowed measurement of the frequency and duration of urination and defecation postures at monthly intervals post operatively (PO) by observers blinded to the surgical interventions.ResultsIn the 6 animals with intact L7 dorsal roots, 3 displayed micturition postures 1 month, 6/6 at 2 and 3 months and 5/6 at 4 months PO. In the 6 animals with the additional L7 dorsal root transections, micturition postures were observed in 2/6 at 1 and 2 months and 3/6 at 3 and 4 months PO. In the L7 dorsal root intact animals, defecation postures were observed in 0/6 at 1 month and 2/6 at 2, 3 and 4 months PO. In the L7 dorsal root transected group, 1/6 showed defecation postures at 1 and 2 months but not at 4 months, and 1/6 showed these postures at 3 and 4 months PO.ConclusionsIn the L7 dorsal root intact animals, although half were unable to sense bladder fullness and 0/6 could not sense bowel fullness at 1 month PO, all were able to sense bladder fullness at 2 and 3 months and all but 1 at 4 months PO, suggesting sprouting of sensory bladder innervation likely from the remaining lower lumbar dorsal root fibers. Fewer dogs with L7 dorsal root transected were able to detect bladder fullness. The ability of 3/6 animals in the L7 dorsal root transected group to sense bladder fullness at 2–4 months PO may be from sensory nerve sprouting or variations in the bladder sensory innervation, as we described previously. Bowel fullness sensation appears to be primarily mediated by sacral sensory innervation.Funding Source(s)NIH 1R01NS070267

Síndrome de Ross en un paciente pediátrico: reporte de caso

Se presenta el caso de un paciente de 6 años de edad con hipohidrosis segmentaria en el hemicuerpo derecho, pupila tónica de Adie e hiporreflexia ipsilateral. Con esta tríada se hizo el diagnóstico clínico de la tríada del síndrome de Ross.
 La importancia de este caso radica en la identificación de la hipohidrosis como una manifestación de un desorden autonómico. Su fisiopatología es la denervación posganglionar de las fibras colinérgicas parasimpáticas entre el ganglio ciliar y el iris (pupila tónica), degeneración presináptica de las fibras de la raíz dorsal que transmiten el impulso al asta ventral (hiporreflexia) y la degeneración de las fibras simpáticas posganglionares de las glándulas sudoríparas, su causa no es clara.
 El curso es crónico, con extensión variable del área dishidrótica. Los pacientes pueden tener compromiso de la termorregulación y alteración en la calidad de vida, por lo que debe enseñarse al paciente y cuidadores estrategias para evitar el sobrecalentamiento corporal.

Computational analysis of kilohertz frequency spinal cord stimulation for chronic pain management.

Kilohertz frequency spinal cord stimulation (KHFSCS) is an emerging therapy for treating refractory neuropathic pain. Although KHFSCS has the potential to improve the lives of patients experiencing debilitating pain, its mechanisms of action are unknown and thus it is difficult to optimize its development. Therefore, the goal of this study was to use a computer model to investigate the direct effects of KHFSCS on specific neural elements of the spinal cord. This computer model consisted of two main components: (1) finite element models of the electric field generated by KHFSCS and (2) multicompartment cable models of axons in the spinal cord. Model analysis permitted systematic investigation into a number of variables (e.g., dorsal cerebrospinal fluid thickness, lead location, fiber collateralization, and fiber size) and their corresponding effects on excitation and conduction block thresholds during KHFSCS. The results of this study suggest that direct excitation of large-diameter dorsal column or dorsal root fibers require high stimulation amplitudes that are at the upper end or outside of the range used in clinical KHFSCS (i.e., 0.5 to 5 mA). Conduction block was only possible within the clinical range for a thin dorsal cerebrospinal fluid layer. These results suggest that clinical KHFSCS may not function through direct activation or conduction block of dorsal column or dorsal root fibers. Although these results should be validated with further studies, the authors propose that additional concepts and/or alternative hypotheses should be considered when examining the pain relief mechanisms of KHFSCS.

Trans-spinal direct current stimulation modifies spinal cord excitability through synaptic and axonal mechanisms.

The spinal cord is extremely complex. Therefore, trans‐spinal direct current stimulation (tsDCS) is expected to produce a multitude of neurophysiological changes. Here, we asked how tsDCS differentially affects synaptic and nonsynaptic transmission. We investigated the effects of tsDCS on synaptically mediated responses by stimulating the medullary longitudinal fascicle and recording responses in the sciatic nerve and triceps and tibialis anterior muscles. Response amplitude was increased during cathodal‐tsDCS (c‐tsDCS), but reduced during anodal‐tsDCS (a‐tsDCS). After‐effects were dependent on the frequency of the test stimulation. c‐tsDCS‐reduced responses evoked by low‐frequency (0.5 Hz) test stimulation and increased responses evoked by high‐frequency (400 Hz) test stimulation. a‐tsDCS had opposite effects. During and after c‐tsDCS, excitability of the lateral funiculus tract (LFT) and dorsal root fibers was increased. However, a‐tsDCS caused a complex response, reducing the excitability of LFT and increasing dorsal root fiber responses. Local DC application on the sciatic nerve showed that the effects of DC on axonal excitability were dependent on polarity, duration of stimulation, temporal profile (during vs. after stimulation), orientation of the current direction relative to the axon and relative to the direction of action potential propagation, distance from the DC electrode, and the local environment of the nervous tissue. Collectively, these results indicate that synaptic as well as axonal mechanisms might play a role in tsDCS‐induced effects. Therefore, this study identified many factors that should be considered in interpreting results of DCS and in designing tsDCS‐based interventions.

Будова та кровопостачання L2-S2 дорзальних корінців спинного мозку щурів різного віку

The paper presents information of hystometryc and electron microscopic research of nerve fibres of spinal cord dorsal roots and their blood circulation system of rats in the postnatal period of ontogenesis. The basic types of nerve fibres are revealed and characterized. Their composition which reflects the close morphological mutually causal structure of nerves and ways of blood microcirculatory is shown. It can determine the character of age-specific processes in the dorsal roots.

Recent advances in understanding of various chronic pain mechanisms through lysophosphatidic acid (LPA) receptor signaling

Lysophosphatidic acid (LPA) receptor (LPA1) signaling plays the key role in initiation of nerve injury-induced neuropathic pain [1-4]. LPA, which is produced in the spinal cord following the sciatic nerve injury causes a calpain-mediated demyelination of dorsal root fibers and sprouting through LPA1 receptor, leading to an induction of synaptic reorganization underlying allodynia. The LPA1 signaling also initiates the up-regulation of Cavα2δ1 in DRG, leading to an enhancement of spinal pain transmission underlying hyperalgesia. Similar LPA1-mediated chronic abnormal pain and underlying mechanisms are observed in mouse models with Meth-A sarcoma surrounding sciatic nerve (cancer model) or with chemotherapy (paclitaxel). Central neuropathic pain following spinal nerve injury is now recently found to include the LPA1-mediated mechanisms. In contrast, (arthritic) inflammatory pain following Complete Freund Adjuvant treatment fails to show the involvement of LPA1 signaling. Thus it seems that many models of neuropathic pain, but not inflammatory pain model include LPA1-mediated mechanisms. Recent studies revealed that another subtype LPA3 receptor plays a crucial role in neuropathic pain mechanisms in terms of LPA biosynthesis. Nerve injury and intrathecal administration of LPA increased the levels of lysophosphatidylcholine (LPC) and LPA in the spinal dorsal horn and dorsal root with peaks at 1 - 2 h. We obtained the evidence for in vitro LPA biosynthesis in spinal dorsal horn and dorsal root as well as in vivo one. In these studies we successfully identified the species of LPC and LPA molecules by use of Mass Spectrometery. Major species are the molecules with lipid chain 16:0, 18:0 or 18:1, and their contents were all time-dependently increased by nerve injury. Interestingly, there was an LPA-induced amplification of LPA biosynthesis through an activation of LPA3 receptor and microglia. The microglial involvement was found to play key roles as an initiation of neuropathic pain mechanisms including LPA3-mediated amplification of LPA biosynthesis.

Electrode alignment of transverse tripoles using a percutaneous triple-lead approach in spinal cord stimulation

The aim of this modeling study is to determine the influence of electrode alignment of transverse tripoles on the paresthesia coverage of the pain area in spinal cord stimulation, using a percutaneous triple-lead approach. Transverse tripoles, comprising a central cathode and two lateral anodes, were modeled on the low-thoracic vertebral region (T10–T12) using percutaneous triple-lead configurations, with the center lead on the spinal cord midline. The triple leads were oriented both aligned and staggered. In the staggered configuration, the anodes were offset either caudally (caudally staggered) or rostrally (rostrally staggered) with respect to the midline cathode. The transverse tripolar field steering with the aligned and staggered configurations enabled the estimation of dorsal column fiber thresholds (IDC) and dorsal root fiber thresholds (IDR) at various anodal current ratios. IDC and IDR were considerably higher for the aligned transverse tripoles as compared to the staggered transverse tripoles. The aligned transverse tripoles facilitated deeper penetration into the medial dorsal columns (DCs). The staggered transverse tripoles always enabled broad and bilateral DC activation, at the expense of mediolateral steerability. The largest DC recruited area was obtained with the rostrally staggered transverse tripole. Transverse tripolar geometries, using percutaneous leads, allow for selective targeting of either medial or lateral DC fibers, if and only if the transverse tripole is aligned. Steering of anodal currents between the lateral leads of the staggered transverse tripoles cannot target medially confined populations of DC fibers in the spinal cord. An aligned transverse tripolar configuration is strongly recommended, because of its ability to provide more post-operative flexibility than other configurations.

Lysophosphatidic Acid as the Initiator of Neuropathic Pain

The injury-induced intense stimulation of spinal cord neurons causes lysophosphatidic acid (LPA) biosynthesis. LPA(1) receptor activation causes demyelination and sprouting of dorsal root fibers, leading to an induction of synaptic reorganization underlying allodynia, in which innocuous (tactile) stimuli cause intense pain. The LPA(1) signal also initiates the up-regulation of Ca(v)α2δ1 in dorsal root ganglion and PKCγ in the dorsal horn, underlying mechanisms for characteristic neuropathic hyperalgesia in myelinated sensory (A-type) fibers. On the other hand, the LPA(3) receptor mediates microglia activation at the early stage after nerve injury and LPA-induced LPA biosynthesis. Thus, both the LPA(1) and LPA(3) receptors play key roles in the initiation step using a feed-forward system for neuropathic pain.

Spinal Microglial Motility is Independent of Neuronal Activity and Plasticity in Adult Mice

Microglia are the resident macrophages in the central nervous system. In the spinal cord dorsal horn, microglia stay in resting condition during physiological sensory processing, and are activated under pathological conditions such as peripheral nerve injury. In cases such as this, the nearby resting microglia increase their motility and accumulate at the site of injury. However, direct evidence to support that nerve activity can enhance the motility of microglia has not yet to be reported. In this study we investigated whether the activation of spinal microglia under in vivo nerve injury may be mimicked by neuronal activity in the spinal cord slice preparation. We found that local application of spinal excitatory neurotransmitters, such as glutamate and substance P did not cause any change in the motility of microglial cells in the spinal cord dorsal horn. The motility of microglial cells is unlikely modulated by other transmitters, neuromodulators and chemokines, because similar applications such as GABA, serotonin, noradrenaline, carbachol, fractalkine or interleukin did not produce any obvious effect. Furthermore, low or high frequency stimulation of spinal dorsal root fibers at noxious intensities failed to cause any enhanced extension or retraction of the microglia processes. By contrast, focal application of ATP triggered rapid and robust activation of microglial cells in the spinal dorsal horn. Our results provide the first evidence that the activation of microglia in the spinal cord after nerve injury is unlikely due solely to neuronal activity, non-neuronal factors are likely responsible for the activation of nerve injury-related microglial cells in the spinal dorsal horn.

Autotaxin and Lysophosphatidic Acid1 receptor-Mediated Demyelination of Dorsal Root Fibers by Sciatic Nerve Injury and Intrathecal Lysophosphatidylcholine

BackgroundAlthough neuropathic pain is frequently observed in demyelinating diseases such as Guillain-Barré syndrome and multiple sclerosis, the molecular basis for the relationship between demyelination and neuropathic pain behaviors is poorly understood. Previously, we found that lysophosphatidic acid receptor (LPA1) signaling initiates sciatic nerve injury-induced neuropathic pain and demyelination.ResultsIn the present study, we have demonstrated that sciatic nerve injury induces marked demyelination accompanied by myelin-associated glycoprotein (MAG) down-regulation and damage of Schwann cell partitioning of C-fiber-containing Remak bundles in the sciatic nerve and dorsal root, but not in the spinal nerve. Demyelination, MAG down-regulation and Remak bundle damage in the dorsal root were abolished in LPA1 receptor-deficient (Lpar1-/-) mice, but these alterations were not observed in sciatic nerve. However, LPA-induced demyelination in ex vivo experiments was observed in the sciatic nerve, spinal nerve and dorsal root, all which express LPA1 transcript and protein. Nerve injury-induced dorsal root demyelination was markedly attenuated in mice heterozygous for autotaxin (atx+/-), which converts lysophosphatidylcholine (LPC) to LPA. Although the addition of LPC to ex vivo cultures of dorsal root fibers in the presence of recombinant ATX caused potent demyelination, it had no significant effect in the absence of ATX. On the other hand, intrathecal injection of LPC caused potent dorsal root demyelination, which was markedly attenuated or abolished in atx+/- or Lpar1-/- mice.ConclusionsThese results suggest that LPA, which is converted from LPC by ATX, activates LPA1 receptors and induces dorsal root demyelination following nerve injury, which causes neuropathic pain.

Differential NR2B subunit expression at dorsal root and ventrolateral funiculus synapses on lumbar motoneurons of neonatal rat

Synapse specific differences in NR2 subunit expression exist in several systems within the mammalian CNS. Here we have studied such differences on motoneurons in the neonatal rat cord using ifenprodil known to inhibit voltage-, use- and glycine-independent responses mediated by NR2B-containing N-methyl- d-aspartate receptors (NMDARs) with high specificity. In neonatal rats (P1–P9), the synapses made by the dorsal root (DR) fibres were more sensitive to ifenprodil than ventrolateral funiculus (VLF) connections on the same motoneuron. DR connections exhibited very little additional blockade to bath-applied MK-801 whereas VLF connections displayed a further decrease in amplitude. This suggests that at this immediate postnatal age, DR synapses on motoneurons contain a higher proportion of ifenprodil-sensitive diheteromeric NR1/NR2B receptors than VLF synapses. Since DR synapses have been shown in other studies to be less mature than VLF synapses on the same motoneuron at this developmental stage, these data are interpreted as indicating that less mature NMDA receptors feature a higher proportion of NR2B subunits which declines as the synapse matures. This novel finding of staggered development of NMDA receptors from different synaptic inputs on the same motoneuron is discussed in the context of its developmental and functional implications.

Mechanosensitive Primary Bladder Afferent Activity in Rats With and Without Spinal Cord Transection

Spinal cord injury induces functional and morphological changes in bladder afferent pathways. However, direct evidence for changes in the excitability of afferent nerve activity primarily originating from the bladder has not been clearly demonstrated. Thus, we determined the characteristics of peripheral mechanosensitive bladder afferents in the pelvic nerve and possible afferent changes in Adelta and C fibers after spinal cord injury. Adult female rats were divided into 2 groups, including spinal cord injured and neurologically intact animals. In the spinal cord injury group the spinal cord was transected at Th9 at 4 weeks before functional experiments. For single unit afferent activity monitoring fine filaments were dissected from the L6 dorsal root and bladder afferent fibers were identified. Single unit afferent activity was studied during constant filling with saline. Two afferent patterns were linked to small phasic increases in intravesical pressure during bladder filling, including accelerated and nonaccelerated types. The incidence of the accelerated type was significantly higher in the spinal cord injury group than in the neurologically intact group regarding Adelta and C fibers. However, we found no relationship between conduction velocity and the functional properties of bladder mechanosensitive afferent fibers in neurologically intact or spinal cord injured rats. Results indicate that mechanosensitive bladder afferent activity has several patterns and is facilitated after spinal cord injury, especially in concert with small bladder contractions (micromotions). The functional properties of these individual afferent fibers are not related in an obvious manner to their conduction velocity and, thus, probably the afferent fiber type.

The dorsal root ganglion in Friedreich’s ataxia

Atrophy of dorsal root ganglia (DRG) and thinning of dorsal roots (DR) are hallmarks of Friedreich's ataxia (FRDA). Many previous authors also emphasized the selective vulnerability of larger neurons in DRG and thicker myelinated DR axons. This report is based on a systematic reexamination of DRG, DR and ventral roots (VR) in 19 genetically confirmed cases of FRDA by immunocytochemistry and single- and double-label immunofluorescence with antibodies to specific proteins of myelin, neurons and axons; S-100alpha as a marker of satellite and Schwann cells; laminin; and the iron-responsive proteins ferritin, mitochondrial ferritin, and ferroportin. Confocal images of axons and myelin allowed the quantitative analysis of fiber density and size, and the extent of DR and VR myelination. A novel technology, high-definition X-ray fluorescence (HDXRF) of polyethylene glycol-embedded fixed tissue, was used to "map" iron in DRG. Unfixed frozen tissue of DRG in three cases was available for the chemical assay of total iron. Proliferation of S-100alpha-positive satellite cells accompanied neuronal destruction in DRG of all FRDA cases. Double-label visualization of peripheral nerve myelin protein 22 and phosphorylated neurofilament protein confirmed the known loss of large myelinated DR fibers, but quantitative fiber counts per unit area did not change. The ratio of myelinated to neurofilament-positive fibers in DR rose significantly from 0.55 to 0.66. In VR of FRDA patients, fiber counts and degree of myelination did not differ from normal. Pooled histograms of axonal perimeters disclosed a shift to thinner fibers in DR, but also a modest excess of smaller axons in VR. Schwann cell cytoplasm in DR of FRDA was depleted while laminin reaction product remained prominent. Numerous small axons clustered around fewer Schwann cells. Ferritin in normal DRG localized to satellite cells, and proliferation of these cells in FRDA caused wide rims of reaction product about degenerating nerve cells. Mitochondrial ferritin was not detectable. Ferroportin was present in the cytoplasm of normal satellite cells and neurons, and in large axons of DR and VR. In FRDA, some DRG neurons lost their cytoplasmic ferroportin immunoreactivity, whereas the cytoplasm of satellite cells remained ferroportin positive. Ferroportin in DR axons disappeared in parallel with atrophy of large fibers. HDXRF of DRG detected regional and diffuse increases in iron fluorescence that matched ferritin expression in satellite cells. The observations support the conclusions that satellite cells and DRG neurons are affected by iron dysmetabolism; and that regeneration and inappropriate myelination of small axons in DR are characteristic of the disease.