Differences between the tactile sensitivity on the anterior torso of normal individuals and those having suffered complete transection of the spinal cord

Using the method of limits and a magnitude estimation procedure, the sense of touch was examined at multiple sites on the anterior torso of normal subjects. Their performance was compared with the performance of individuals having experienced a functionally complete spinal cord transection more than 6 months prior to the tests. Near the insentient regions of the spinal cord-injured patients there was a zone wherein the threshold for light touch was elevated and variable. Within this same transition zone, estimates of the magnitude of a brushing stimulus increased as a linear function of distance from the border for approximately 12 cm away from insentient skin. Throughout the rest of the thorax, spinal cord-injured patients displayed touch thresholds 67% higher than normals and, at the same test sites, spinal cord-injured patients offered estimates of the intensity of the brushing stimulus that averaged 62% higher than normal subjects. The greater intensity of the sensations experienced by spinal cord-injured patients with even very weak stimuli and the smaller range within which they were able to scale stimulus intensity, produced a situation wherein the patients made frequent errors of judgement even on skin regions far from the body parts affected by the lesion. These observations support the hypothesis that spinal cord lesions interrupt tonic modulatory mechanisms having global influences on the sense of touch. This loss produces an elevation of the touch threshold and a reduction of the normal dynamic range of tactile sensory perception for all skin surfaces on the anterior torso.     

Differences in the sensations of warmth on the anterior torso of normal and spinal-cord transected individuals

The threshold to warming was measured at 10 sites on the anterior torso between the umbilicus and the clavicle of normal and spinal-cord transected individuals. In normal individuals, thresholds were higher on the thorax than on the abdomen. Men had higher and more variable thresholds than women. Magnitude estimations of supra-threshold stimuli showed that men offer verbal estimates of warmth that are about half of the size of the estimates given by women to the same stimuli. The psychometric function shows that in women, the sensation of warmth grows more rapidly than in men after starting from a higher initial value. After spinal-cord injury, thresholds for detection of warming were elevated. This effect was most noticeable within 8 cm of the anesthetic zone, but farther away, thresholds were still elevated but uniform as a function of distance, being about 30% higher than in normal individuals. After spinal-cord injury, the psychometric functions show that small stimuli elicit relatively large sensations and that these sensations grow more slowly with increasing skin temperatures than for normal individuals. Thus, for small warm stimuli spinal-cord-injured patients (both men and women) have a response similar to normal women but the slope of the psychometric function is flat, being similar to the slope observed for normal men.     

The effects of heat-induced pain on the detectability,discriminability, and sensation magnitude of vibrotactile stimuli

The effects of heat-induced pain on absolute thresholds, sensation magnitudes and amplitude-difference thresholds were measured at 10 and 100 Hz. Consistent with previous results, heat-induced pain elevated the absolute thresholds by approximately 8.0 dB and lessened the magnitudes of tactile sensations during pain as compared to the non-painful condition. In contrast to these effects, the discriminability of change in the intensity of the vibrotactile stimuli was unaffected by the presence of pain indicating that the effect of pain on tactile sensations is more likely due to sensory rather than cognitive processes (i.e., attention) and that the mechanisms underlying tactile sensitivity as compared to discriminability are different.     

Sensory function above lesion level in spinal cord injury patients with and without pain

Patients with spinal cord injury (SCI) may or may not develop central neuropathic pain despite having cord lesions of apparently the same site, extension and nature. The consequences of the cord lesion in the central nervous system and the mechanisms underlying pain are unclear. In this study, we examined sensory detection and pain thresholds above injury level in 17 SCI patients with central neuropathic pain, in 18 SCI patients without neuropathic pain, and in 20 control subjects without injury and pain. The SCI pain group had significantly higher cold and warm detection thresholds compared with the SCI pain free group and controls and higher tactile detection thresholds compared with the SCI pain free group. No difference in pain or pain tolerance thresholds was seen among pain and pain free SCI patients. These data suggest changes in somatosensory function in dermatomes rostral to the segmental injury level linked to the presence of central neuropathic pain in SCI patients. The results are discussed in relation to current concepts of pain inhibitory and facilitating systems.     

Differences in the sensations of warmth on the anterior torso of normal and spinal-cord transected individuals

The threshold to warming was measured at 10 sites on the anterior torso between the umbilicus and the clavicle of normal and spinal-cord transected individuals. In normal individuals, thresholds were higher on the thorax than on the abdomen. Men had higher and more variable thresholds than women. Magnitude estimations of supra-threshold stimuli showed that men offer verbal estimates of warmth that are about half of the size of the estimates given by women to the same stimuli. The psychometric function shows that in women, the sensation of warmth grows more rapidly than in men after starting from a higher initial value. After spinal-cord injury, thresholds for detection of warming were elevated. This effect was most noticeable within 8 cm of the anesthetic zone, but farther away, thresholds were still elevated but uniform as a function of distance, being about 30% higher than in normal individuals. After spinal-cord injury, the psychometric functions show that small stimuli elicit relatively large sensations and that these sensations grow more slowly with increasing skin temperatures than for normal individuals. Thus, for small warm stimuli spinal-cord-injured patients (both men and women) have a response similar to normal women but the slope of the psychometric function is flat, being similar to the slope observed for normal men.     

Reactions of the rat musculoskeletal system to compressive spinal cord injury (SCI) and whole body vibration (WBV) therapy

Traumatic spinal cord injury (SCI) causes a loss of locomotor function with associated compromise of the musculo-skeletal system. Whole body vibration (WBV) is a potential therapy following SCI, but little is known about its effects on the musculo-skeletal system. Here, we examined locomotor recovery and the musculo-skeletal system after thoracic (T7-9) compression SCI in adult rats. Daily WBV was started at 1, 7, 14 and 28 days after injury (WBV1-WBV28 respectively) and continued over a 12-week post-injury period. Intact rats, rats with SCI but no WBV (sham-treated) and a group that received passive flexion and extension (PFE) of their hind limbs served as controls. Compared to sham-treated rats, neither WBV nor PFE improved motor function. Only WBV14 and PFE improved body support. In line with earlier studies we failed to detect signs of soleus muscle atrophy (weight, cross sectional diameter, total amount of fibers, mean fiber diameter) or bone loss in the femur (length, weight, bone mineral density). One possible explanation is that, despite of injury extent, the preservation of some axons in the white matter, in combination with quadripedal locomotion, may provide sufficient trophic and neuronal support for the musculoskeletal system.     

Identification of key pathways and RNAs associated with skeletal muscle atrophy after spinal cord injury

Objective:This study was performed to investigate the potential key molecules involved in the progression of skeletal muscle atrophy after SCI.Methods:Based on {"type":"entrez-geo","attrs":{"text":"GSE21497","term_id":"21497"}}GSE21497 dataset, the DEmRNAs and DElncRNAs were screened after differentially expressed analysis. Then the enrichment analyses were performed on DEmRNAs. Then the PPI network and ceRNA network were constructed. Finally, the DGIdb was utilized to predict drug-gene interactions.Results:A total of 412 DEmRNAs and 21 DElncRNAs were obtained. The DEmRNAs were significantly enriched in MAPK signaling pathway and FoxO signaling pathway. In addition, UBE2D1, JUN, and FBXO32 had higher node degrees in PPI network, and the top 20 genes with high degree were significantly enriched in FoxO signaling pathway and Endometrial cancer. Moreover, FOXO3 was regulated by hsa-miR-1207-5p and hsa-miR-1207-5p was regulated by lncRNA RP11-253E3.3 in ceRNA network. Finally, 37 drug-gene interactions were obtained based on the 26 genes in ceRNA network.Conclusion:UBE2D1, JUN, and FBXO32 are likely to be related to the progression of skeletal muscle atrophy after SCI, and activating of MAPK signaling pathway, Endometrial cancer and FoxO signaling pathway may induce skeletal muscle inflammation, apoptosis, autophagy and atrophy after SCI. Moreover, RP11-253E3.3-hsa-miR-1207-5p-FOXO3 axis may be a promising therapeutic target for skeletal muscle atrophy after SCI.     

Time course changes to structural,mechanical and material properties of bone in rats after complete spinal cord injury

Objective:Characterise the spatiotemporal trabecular and cortical bone responses to complete spinal cord injury (SCI) in young rats.Methods:8-week-old male Wistar rats received T9-transection SCI and were euthanised 2-, 6-, 10- or 16-weeks post-surgery. Outcome measures were assessed using micro-computed tomography, mechanical testing, serum markers and Fourier-transform infrared spectroscopy.Results:The trabecular and cortical bone responses to SCI are site-specific. Metaphyseal trabecular BV/TV was 59% lower, characterised by fewer and thinner trabeculae at 2-weeks post-SCI, while epiphyseal BV/TV was 23% lower with maintained connectivity. At later-time points, metaphyseal BV/TV remained unchanged, while epiphyseal BV/TV increased. The total area of metaphyseal and mid-diaphyseal cortical bone were lower from 2-weeks and between 6- and 10-weeks post-SCI, respectively. This suggested that SCI-induced bone changes observed in the rat model were not solely attributable to bone loss, but also to suppressed bone growth. No tissue mineral density differences were observed at any time-point, suggesting that decreased whole-bone mechanical properties were primarily the result of changes to the spatial distribution of bone.Conclusion:Young SCI rat trabecular bone changes resemble those observed clinically in adult and paediatric SCI, while cortical bone changes resemble paediatric SCI only.     

Single session exercises and concurrent functional electrical stimulation are more effective on muscles’ force generation than only exercises in spinal cord injured persons: a feasibility study

Objectives:To evaluate impact of first therapy session, containing functional electrical stimulation (FES) and therapeutic exercises (TE) on erector spinae (ES) and rectus abdominis (RA) force generation in persons with spinal cord injury (SCI).Methods:Five men with SCI were divided in two groups - FES+TE received concurrent FES on ES and RA and TE, TE only TE. Participants performed exercises for improving sitting balance and posture. Muscles’ electrical activity was evaluated by electromyography; amplitude (AEMG) and median frequency (MF) were used for analysis.Results:AEMG of ES left (L) increased 292.9% (g=-0.92), right (R) 175% (g=-1.01), RA L 314.3% (g=-0,81, P<0.05), R 266.7% (g=-0.08) in FES+TE. AEMG of ES L increased 47.6% (g=-0.46), R 96.4% (g=-0.95); RA L 7.1% (g=-0.97), but R decreased 6.7% (g=0.12) in TE. MF of ES L increased 108.5% (g=-0.74), R 184% (g=-1.25); RA L 886.7% (g=3-05, P<0.05), R 817.6% (g=-2.55, P<0.05) in FES+TE. MF of ES L increased 95.2% (g=-1.02), R 161.4% (g=-1.64); RA L 3,2% (g=-0.06), R 30.8% (g=-0.46) in TE.Conclusions:In SCI persons, single session exercises and concurrent functional electrical stimulation may be more effective on muscles` force generation than only exercises. However, replication of the results is needed before clinical implementation.     

An electron microscopic study of macroglia and microglia in the lateral funiculus of the developing spinal cord in the fetal monkey

Summary An electron-microscopic study has been made of the glial cells in the developing lateral funiculus of the cervical spinal cord in fetal rhesus monkeys. The various macroglial cell types, their precursor cells, and microglia are discussed in detail. An astrocytic lineage is proposed in which glioblasts present in the lateral funiculus give rise to astroblasts that then develop into mature astrocytes. Oligoblasts apparently migrate into the lateral funiculus as such and develop into active oligocytes. The active oligocytes become most predominant during the initial stages of myelinogenesis and are in direct continuity with developing myelin. The active oligocytes develop into mature oligocytes after myelination is completed. Microglia cells are present throughout development as three forms; resting microglia, globose microglia, and active microglia. The globose and active microglia predominates at specific times early in development when degeneration of apparent neuronal processes is taking place. The microglia cells are characterized by dense nuclear chromatin clumps, lipid inclusion bodies, dense vesicles, and, often, intracellular debris.Supported in part by a Parson Trust Endowment Research Grant at the University of South Dakota School of Medicine. The author gratefully acknowledges the help of Dr. Ronald DiGiacomo who was responsible for the surgery involved in the fetal deliveries.     

Effects of different vibration frequencies on spinal cord reflex circuits and thermoalgesic perception

Objectives:We studied the effect of different vibration frequencies on spinal cord excitability and heat pain perception. We hypothesized that the effects of vibration on spinal cord reflexes, and, also those on heat pain perception, depend on vibration frequency.Methods:In 9 healthy subjects, we applied vibration over the tibialis anterior muscle at three different frequencies (50, 150, or 250 Hz) on spinal cord reflex excitably, tested with the H reflex and the T wave in the soleus muscle, as well as on sensory and pain perception, tested by measuring warm perception (WT) and heat pain perception thresholds, (HPT) in sites rostral and caudal to vibration. Exams were carried out before, during, and after vibration.Results:The amplitude of the H reflex and T wave significantly decreased during vibration in comparison to baseline. Low frequencies (50 and 150Hz) induced greater reflex suppression than high frequency (250Hz). No significant changes were observed on WT and HPT.Conclusions:The effects of vibratory stimulation can be summarized as frequency-related suppression of the spinal cord excitability without an effect on warm and heat pain perception. The present results may help to design vibration-related interventions intended to diminish spinal cord reflex excitability in spastic patients.     

Influence of complete spinal cord injury on skeletal muscle cross-sectional area within the first 6 months of injury

In this study we examined the influence of complete spinal cord injury (SCI) on affected skeletal muscle morphology within 6 months of SCI. Magnetic resonance (MR) images of the leg and thigh were taken as soon as patients were clinically stable, on average 6 weeks post injury, and 11 and 24 weeks after SCI to assess average muscle cross-sectional area (CSA). MR images were also taken from nine able-bodied controls at two time points separated from one another by 18 weeks. The controls showed no change in any variable over time. The patients showed differential atrophy (P = 0.0001) of the ankle plantar or dorsi flexor muscles. The average CSA of m. gastrocnemius and m. soleus decreased by 24% and 12%, respectively (P = 0.0001). The m. tibialis anterior CSA showed no change (P = 0.3644). As a result of this muscle-specific atrophy, the ratio of average CSA of m. gastrocnemius to m. soleus, m. gastrocnemius to m. tibialis anterior and m. soleus to m. tibialis anterior declined (P = 0.0001). The average CSA of m, quadriceps femoris, the hamstring muscle group and the adductor muscle group decreased by 16%, 14% and 16%, respectively (P< or =0.0045). No differential atrophy was observed among these thigh muscle groups, thus the ratio of their CSAs did not change (P = 0.6210). The average CSA of atrophied skeletal muscle in the patients was 45-80% of that of age- and weight-matched able-bodied controls 24 weeks after injury. In conclusion, the results of this study suggest that there is marked loss of contractile protein early after SCI which differs among affected skeletal muscles. While the mechanism(s) responsible for loss of muscle size are not clear, it is suggested that the development of muscular imbalance as well as diminution of muscle mass would compromise force potential early after SCI.     

Terminal processes of serotonin neurons in the caudal spinal cord of the molly,Poecilia latipinna,project to the leptomeninges and urophysis

Summary The caudal neurosecretory complex of poeciliids has previously been shown to be innervated by extranuclear and intrinsic serotonergic projections. In the present study, immunohistochemical techniques were used to characterize fibers originating from serotonin neurons intrinsic to the caudal spinal cord. Bipolar and multipolar neurons were oriented ventromedially, and contained numerous large granular vesicles. Three types of serotonergic fibers were distinguished based on their distribution and morphology. Intrinsic Type-A fibers branched into varicose segments near the ventrolateral surface of the spinal cord and contacted the basal lamina beneath the leptomeninges. Type-B fibers coursed longitudinally to enter the urophysis, where they diverged and terminated around fenestrated capillaries. Labelled vesicles in Type-A and Type-B terminals were the same size as those in labelled cells and in unlabelled neurosecretory terminals in the urophysis. Type-C small varicose fibers branched within the neuropil of the caudal neurosecretory complex. Serotonin may be secreted into the submeningeal cerebrospinal fluid, the urophysis, and the caudal vein by Type-A and Type-B fibers, whereas, Type-C fibers may be processes of serotonergic interneurons in the neuroendocrine nucleus. The possibility that urotensins I and II or arginine vasotocin were colocalized in the processes of the intrinsic serotonin neurons was investigated immunohistochemically. The negative results of these experiments suggest that serotonin-containing neurons may represent a neurochemically distinct subpopulation in the caudal neurosecretory complex.     

Probing the influence of myelin and glia on the tensile properties of the spinal cord

Although glia have been historically classified as the structurally supporting cells of the central nervous system, their role in tissue mechanics is still largely unstudied. The influence of myelin and glia on the mechanical properties of spinal cord tissue was examined by testing embryonic day 18 chick embryo spinal cords in uniaxial tension following disruption of the glial matrix using either ethidium bromide (EB) or an antibody against galactocerebroside (αGalC) in the presence of complement. Demyelination was confirmed by myelin basic protein immunoreactivity and quantified using osmium tetroxide staining. A substantial loss of astrocytes and oligodendrocytes concurrent with demyelination was observed following EB injection but not αGalC injection. No morphological changes were observed following injection of saline or IgG with complement as controls for EB and αGalC. Demyelinated spinal cords demonstrated significantly lower stiffness and ultimate tensile stress than myelinated spinal cords. No significant differences were observed in the tensile response between the two demyelinating protocols. The results demonstrate that the glial matrix provides significant mechanical support to the spinal cord, and suggests that myelin and cellular coupling of axons via the glial matrix in large part dictates the tensile response of the tissue.     

Effects of ghrelin and des-acyl ghrelin on neurogenesis of the rat fetal spinal cord

Expressions of the growth hormone secretagogue receptor (GHS-R) mRNA and its protein were confirmed in rat fetal spinal cord tissues by RT-PCR and immunohistochemistry. In vitro, over 3 nM ghrelin and des-acyl ghrelin induced significant proliferation of primary cultured cells from the fetal spinal cord. The proliferating cells were then double-stained using antibodies against the neuronal precursor marker, nestin, and the cell proliferation marker, 5-bromo-2'-deoxyuridine (BrdU), and the nestin-positive cells were also found to be co-stained with antibody against GHS-R. Furthermore, binding studies using [125I]des-acyl ghrelin indicated the presence of a specific binding site for des-acyl ghrelin, and confirmed that the binding was displaced with unlabeled des-acyl ghrelin or ghrelin. These results indicate that ghrelin and des-acyl ghrelin induce proliferation of neuronal precursor cells that is both dependent and independent of GHS-R, suggesting that both ghrelin and des-acyl ghrelin are involved in neurogenesis of the fetal spinal cord.     

Wnt/BMP signal integration regulates the balance between proliferation and differentiation of neuroepithelial cells in the dorsal spinal cord

Multiple signaling pathways regulate proliferation and differentiation of neural progenitor cells during early development of the central nervous system (CNS). In the spinal cord, dorsal signaling by bone morphogenic protein (BMP) acts primarily as a patterning signal, while canonical Wnt signaling promotes cell cycle progression in stem and progenitor cells. However, overexpression of Wnt factors or, as shown here, stabilization of the Wnt signaling component beta-catenin has a more prominent effect in the ventral than in the dorsal spinal cord, revealing local differences in signal interpretation. Intriguingly, Wnt signaling is associated with BMP signal activation in the dorsal spinal cord. This points to a spatially restricted interaction between these pathways. Indeed, BMP counteracts proliferation promoted by Wnt in spinal cord neuroepithelial cells. Conversely, Wnt antagonizes BMP-dependent neuronal differentiation. Thus, a mutually inhibitory crosstalk between Wnt and BMP signaling controls the balance between proliferation and differentiation. A model emerges in which dorsal Wnt/BMP signal integration links growth and patterning, thereby maintaining undifferentiated and slow-cycling neural progenitors that form the dorsal confines of the developing spinal cord.     

Influence of spinal cord transection on the presence and axonal transport of CGRP-, chromogranin A-, VIP-, synapsin I-, and synaptophysin-like immunoreactivities in rat motor nerve

Using immunofluorescence and cytofluorimetric scanning (CFS), we investigated the short-term (1-7 days) influence of lower thoracic spinal cord transection on lumbar motor neurons. The content of calcitonin gene-related peptide- (CGRP) like immunoreactivity (LI), chromogranin A (Chr A) -LI, vasoactive intestinal polypeptide (VIP)-LI, Syn I-LI, and synaptophysin (p38)-LI in motor perikarya, and the anterograde and retrograde axonal transport of these substances in the sciatic nerve, were studied in nerve crush (6 h) experiments. During the week after transection, CGRP-LI in perikarya decreased, whereas Chr A-LI increased. VIP-LI, co-localized with Chr A-LI in motor perikarya, did not change after transection. The antero- and retrograde transport of CGRP-LI in the sciatic nerve, occurring in both motor and sensory axons, appeared unchanged in cytofluorimetric scanning (CFS) graphs, but the microscopical picture clearly showed that large motor axons had a decreased content of CGRP-LI at 3 and 7 days posttransection, whereas thinner axons were unchanged in fluorescence intensity. The anterograde transport of Chr A-LI, present in both motor and postganglionic adrenergic axons, was decreased 1 and 3 days after lesion, but returned to control by day 7. There was a marked decrease in anterograde transport of VIP-LI, present mainly in postganglionic sympathetic axons, at day 3, but at 7 days transport was normal. The amounts of transported p38, the synaptic vesicle marker, were in the normal range during the whole period. Syn I-LI accumulation anterogradely was somewhat decreased at 3 and 7 days posttransection, and at 1 day the retrograde accumulation was significantly increased. The results suggest that removal of supraspinal input to intact lower motor neurons causes alterations in metabolism and axonal transport of organelle-associated substances, partly probably related to the complex pattern of transmitter leakage from degenerating, descending nerve terminals. These alterations appear to take place also in postganglionic sympathetic neurons in the sciatic nerve, that originate in the lumbar sympathetic chain. © 1992 John Wiley & Sons, Inc.