End-Structure of Afferent Axons Injured in the Peripheral and Central Nervous System

The end-structure of afferent axons chronically severed in the rat sciatic nerve or dorsal column (DC) was visualized by centrifugal transport of horseradish peroxidase (HRP) or wheatgerm agglutinin conjugated to HRP (WGA:HRP) injected into the L₄ or L₅ dorsal root ganglion. Nerve regeneration was prevented and neuroma formation encouraged by tightly ligating the cut nerve end. For the first few weeks postoperative, the time during which afferents trapped in a nerve-end neuroma generate their most intense ectopic impulse barrage, the developing neuroma was dominated by swollen terminal end-bulbs. There was some axonal dying-back, retrograde fiber growth, and terminal sprouting, but little preterminal branching. The rich tangle of fine preterminal branches usually thought of in relation to nerve-end neuromas did not elaborate until several months postoperative, a time when the neuroma is relatively quiescent electrically. Afferents cut in the DC, which never develop dramatic ectopic electrical activity, showed morphological peculiarities similar to nerve-end neuromas during the early postoperative period, including retrograde fiber growth and minimal sprouting. They did not, however, go on to form luxuriant branches. These data provide preliminary clues as to the structure of the ectopic impulse-generating mechanism thought to underlie paresthesias and pain associated with peripheral nerve injury.     

Nerve growth factor in glia and inflammatory cells of the injured rat spinal cord

Nerve growth factor (NGF) is crucial for the development of sympathetic and small-diameter sensory neurons and for maintenance of their mature phenotype. Its role in generating neuronal pathophysiology is less well understood. After spinal cord injury, central processes of primary afferent fibers sprout into the dorsal horn, contributing to the development of autonomic dysfunctions and pain. NGF may promote these states as it stimulates sprouting of small-diameter afferent fibers and its concentration in the spinal cord increases after cord injury. The cells responsible for this increase must be identified to develop a strategy to prevent the afferent sprouting. Using immunocytochemistry, we identified cells containing NGF in spinal cord sections from intact rats and from rats 1 and 2 weeks after high thoracic cord transection. In intact rats, this neurotrophin was present in a few ramified microglia and in putative Schwann cells in the dorsal root. Within and close to the lesion of cord-injured rats, NGF was in many activated, ramified microglia, in a subset of astrocytes, and in small, round cells that were neither glia nor macrophages. NGF-immunoreactive putative Schwann cells were prevalent throughout the thoracolumbar cord in the dorsal roots and the dorsal root entry zones. Oligodendrocytes were never immunoreactive for this protein. Therapeutic strategies targeting spinal cord cells that produce NGF may prevent primary afferent sprouting and resulting clinical disorders after cord injury.     

Spinal regions involved in baroreflex control of renal sympathetic nerve activity in the rat

Spinal cord injury causes debilitating cardiovascular disturbances. The etiology of these disturbances remains obscure, partly because the locations of spinal cord pathways important for sympathetic control of cardiovascular function have not been thoroughly studied. To elucidate these pathways, we examined regions of the thoracic spinal cord important for reflex sympathetic control of arterial pressure (AP). In anesthetized rats, baroreceptor relationships between pharmacologically induced changes in AP and changes in left renal sympathetic nerve activity (RSNA) were generated in spinally intact rats and after acute surgical hemisection of either the dorsal, left, or right T8 spinal cord. None of these individual spinal lesions prevented the baroreceptor-mediated increases in RSNA caused by decreases in AP. Thus, baroreceptor-mediated increases in RSNA in rats are mediated by relatively diffuse, bilateral, descending, excitatory projections. The ability to reduce RSNA at increased AP was impaired after both dorsal and left hemisections, and baroreceptor gain was significantly decreased. Baroreceptor-induced maximum decreases in RSNA were not affected by right hemisections. However, baroreflex gain was impaired. Because both dorsal and left hemisections, but not right hemisections, attenuated the decrease in RSNA at elevated AP, we conclude that pathways involved in the tonic inhibition of spinal sources of sympathetic activity descend ipsilaterally in the dorsal spinal cord. Our results show that many lesions that do not fully transect the spinal cord spare portions of both descending excitatory pathways that may prevent orthostatic hypotension and descending inhibitory pathways that reduce the incidence of autonomic dysreflexia.     

Trigeminal primary afferent projections to the spinal cord of the frog,Rana ridibunda

The distribution in the spinal cord of the trigeminal primary projections in the frog Rana ridibunda was studied by means of the anterograde transport of horseradish peroxidase (HRP). Upon entering the medulla via the single trigeminal root, a conspicuous descending tract that reaches the cervical spinal cord segments is established. This projection arises in the ophthalmic (V1), maxillary (V2), and mandibular (V3) trigeminal nerve subdivisions. In the spinal cord, only a minor somatotopic arrangement of the trigeminal fibers was observed, with the fibers arising in V3 terminating somewhat more medially than those from V1 and V2. A dense projection to the medial aspect of the spinal cord, above the central canal, primarily involves V3. Each trigeminal branch sends projections at cervical levels to the contralateral dorsal field, and those from V2 are most abundant. Bilateral experiments with HRP application show convergence of primary trigeminal and spinal afferents within the dorsal field of the spinal cord. The pattern of arrangement of the trigeminal primary afferent fibers in the spinal cord of this frog largely resembles that of amniotes. However, the organization seems simpler and the slight somatotopic distribution of V1, V2, and V3 fibers is similar to the condition in other anamniotes. © 1993 Wiley-Liss, Inc.     

Characteristics of the potential of the dorsal surface of the spinal cord in a chronic deficit of afferent influences

The changes of spinal cord dorsal potential (SCDP) has been studied on white rats to the posterior root stimulation at different intervals after sciatic nerve cutting. The increase of threshold, the decrease of amplitude, the growth of duration in some components of SCDP have been revealed on the site of the cutting. These changes were manifested at a less degree on the contralateral cutting site. A conclusion concerning the relative resistance of the spinal cord afferent system to the prolonged absence of peripheral afferent influence has been drawn.     

Phrenic nerve afferents elicited cord dorsum potential in the cat cervical spinal cord

Background  

The diaphragm has sensory innervation from mechanoreceptors with myelinated axons entering the spinal cord via the phrenic nerve that project to the thalamus and somatosensory cortex. It was hypothesized that phrenic nerve afferent (PnA) projection to the central nervous system is via the spinal dorsal column pathway.     

大鼠脊髓诱发电位与脊髓损伤的关系——Ⅲ.脊髓局部损毁后电位的变化及电位来源分析

本文描述了大鼠脊髓L_1节段后柱、后索、侧索和前角的诱发电位及其损伤后的变化,并观察了切断L_4、L_5脊神经背、腹根与横断高位颈髓对电位的影响,以进行行电位来源分析。结果可见,上述四个区域的诱发电位基本由早反应三相波和晚反应组成。分别电解损毁这些部位后,电位波幅均普遍降低,晚期反应较早反应降低明显。后柱或后索受损对电位影响最大。局部损毁后可见L_1及T_(13)水平的硬膜上电位改变明显,尤其晚反应减弱、波峰平坦。反应时值与潜伏时未见明显改变。切断L_4脊神经背、腹根后、电位基本消失。去大脑对电位未见明显影响。结果表明,刺激坐骨神经诱发的脊髓电位起源于低位腰段传入神经和脊髓内多通路的兴奋传导,在一定程度上受腹根逆行活动的影响,与大脑及脊髓下行传导束活动无直接联系。脊髓诱发电位的幅度与波形改变可作为脊髓损伤的判断指标之一。     

Trigeminal projections to contralateral dorsal horn: central extent, peripheral origins, and plasticity

Prior studies have documented a trigeminal (V) mandibular primary afferent projection to the dorsomedial portion of the contralateral medullary and cervical dorsal horns in cat, hamster, and rat. We now report the existence of a much more substantial V ophthalmic primary afferent projection to the ventrolateral portion of contralateral medullary and cervical dorsal horns in rat. Horseradish peroxidase (HRP) injections into the V ganglion or V brainstem complex anterogradely labeled a fascicle of primary afferent axons that exited the caudal ventrolateral V spinal tract to form a rostrocaudally continuous, transversely oriented, V primary afferent decussation. These fibers terminated most heavily in laminae III-V of the ventrolateral dorsal horn in contralateral caudal medulla and the first and second cervical segments. Retrograde tracing with diamidino yellow (DY) or fluorogold and anterograde tracing with Phaseolus vulgaris leucoagglutinin also demonstrated a substantial commissural projection of central origin in medullary dorsal horn laminae I-VII. The latter projection had a more diffuse trajectory and termination pattern than that of the V primary afferent decussation. Unilateral HRP injections into medullary and cervical dorsal horns also retrogradely labeled V primary afferent collaterals contralateral to the injection site in corresponding regions of dorsal horn, and also in ventromedial interpolaris, oralis, and principalis, rostral to their decussation. Axons (1.5 +/- 0.8 microns mean diameter; 0.4-3.9 microns range) therefore terminated both ipsi- and contralateral to their cells of origin. These HRP injections also labeled an average of 40.4 +/- 13.0 V ganglion cells (mean +/- SD, corrected for split somata) in dorsomedial, ophthalmic regions of the contralateral ganglion. Their mean diameter was slightly larger than that of cells labeled ipsilaterally (29.9 vs. 26.3 microns). Double-labeling studies assessed possible ophthalmic receptor surfaces innervated by centrally crossing primary afferents. DY was injected into right medullary and cervical dorsal horns, and HRP was applied to either the left cornea, the ethmoid nerve, or the dura overlying cerebral cortex. Though DY labeled from 75 to 125 left ganglion cells per animal, no cells were double-labeled. All of these findings suggest that nociceptive-specific ganglion cells are not a source of the crossed ophthalmic primary afferent projection. Unilateral transection of the infraorbital nerve on the day of birth did not alter the crossed primary afferent projection to the partially deafferented side of the brainstem. This is further evidence of an absence of central sprouting in spared V primary afferents following neonatal V deafferentation.     

Comparison of [3H]resiniferatoxin binding to spinal cord and dorsal root ganglia of newborn and adult rats

Capsaicin is frequently used in neurobiological investigations to selectively inhibit response by the primary sensory afferent neurons. The effectiveness of treatment depends significantly on the age of the animals; newborns are both quantitatively and qualitatively more sensitive than adults. In the present study, we used the [³H]resiniferatoxin binding assay to determine whether this different susceptibility to capsaicin between newborns and adult animals may reflect differences either in receptor affinity or density. We report here that whole spinal cord membranes of neonates bound [³H]RTX with similar affinity and positive cooperativity as did the spinal cord membranes from adult animals (K_d values were 24.8 ± 3.7 and 26.8 ± 4.8 pM, respectively; Hill coefficients were 2.25 ± 0.03 and 2.17 ± 0.05, respectively). However, the receptor density was three - fold higher in the spinal cord membranes of neonates than of adult rats (B_max values were 142 ± 13 and 43 ± 3 fmol/mg protein, respectively). We found no significant difference in the [³H]RTX binding properties of dorsal root ganglia membranes of newborn and adult animals. Our results suggest than a higher density of the vanilloid receptor in the spinal cord (but not in the dorsal root ganglia) of newborn animals may contribute to the quantitative differences between the sensitivity of adult animals and neonates.     

End-structure of afferent axons injured in the peripheral and central nervous system

The end-structure of afferent axons chronically severed in the rat sciatic nerve or dorsal column (DC) was visualized by centrifugal transport of horseradish peroxidase (HRP) or wheatgerm agglutinin conjugated to HRP (WGA:HRP) injected into the L4 or L5 dorsal root ganglion. Nerve regeneration was prevented and neuroma formation encouraged by tightly ligating the cut nerve end. For the first few weeks postoperative, the time during which afferents trapped in a nerve-end neuroma generate their most intense ectopic impulse barrage, the developing neuroma was dominated by swollen terminal end-bulbs. There was some axonal dying-back, retrograde fiber growth, and terminal sprouting, but little preterminal branching. The rich tangle of fine preterminal branches usually thought of in relation to nerve-end neuromas did not elaborate until several months postoperative, a time when the neuroma is relatively quiescent electrically. Afferents cut in the DC, which never develop dramatic ectopic electrical activity, showed morphological peculiarities similar to nerve-end neuromas during the early postoperative period, including retrograde fiber growth and minimal sprouting. They did not, however, go on to form luxuriant branches. These data provide preliminary clues as to the structure of the ectopic impulse-generating mechanism thought to underlie paresthesias and pain associated with peripheral nerve injury.     

Increased spinal expression of c-Fos following stimulation of the lower urinary tract in chronic spinal cord-injured rats

c-Fos expression was studied in the lumbar and sacral spinal cord regions involved in processing afferent input from the lower urinary tract and a comparison was made between spinal cord-injured (SCI) animals and control animals with intact neuraxes. Afferent pathways from the lower urinary tract were activated either by insertion of a catheter through the urethra into the urinary bladder or by catheterisation plus induction of reflex micturition contractions by intravesical saline infusion. Placement of a catheter alone elicited Fos expression in a similar number of neurones in SCI and control rats mainly in the medial dorsal horn (MDH) and dorsal commissure (DCM) in the segments L1–2 and L5–S1 with a maximum in L5. Additional saline infusion induced low-frequency, high-amplitude, rhythmic bladder contractions of long duration in the rats with intact spinal cords, whereas in SCI rats, bladder distension elicited reflex contractions at a higher frequency, smaller amplitude and shorter duration. However, the basal and mean bladder pressure, as well as the total contraction time relative to the whole recording time, was not significantly different. Distension-induced bladder contractions markedly increased Fos expression primarily in the spinal segments L5–S1 in the control rats, where the majority of bladder and urethral afferent fibres terminates. Fos-positive cells were located in the MDH, lateral dorsal horn (LDH), DCM and the lateral aspect of laminae V–VII. Compared to controls, Fos expression after spinal cord injury (SCI) occurred in a significantly greater number of neurones throughout the segments L3–S1 following induction of bladder reflexes. The greatest proportional increase in the number of Fos-positive cells occurred in L3–5 which normally receive only little afferent input from the urinary bladder. Cell numbers predominantly increased in the LDH and lateral lamina V–VII. The data are consistent with the concept of a neuroplastic reorganisation of spinal pathways after SCI. Unmasking of silent synapses or formation of new connections by afferent axonal sprouting caudal to the lesion, as evident from the increased numbers of cells expressing Fos after bladder distension, could be factors underlying the emergence of reflexogenic micturition in chronic SCI rats. Accepted: 27 May 1999     

Plasticity and emerging role of BKCa channels in nociceptive control in neuropathic pain

Large‐conductance Ca²⁺‐activated K⁺ (BK_Ca, MaxiK) channels are important for the regulation of neuronal excitability. Peripheral nerve injury causes plasticity of primary afferent neurons and spinal dorsal horn neurons, leading to central sensitization and neuropathic pain. However, little is known about changes in the BK_Ca channels in the dorsal root ganglion (DRG) and spinal dorsal horn and their role in the control of nociception in neuropathic pain. Here we show that L5 and L6 spinal nerve ligation in rats resulted in a substantial reduction in both the mRNA and protein levels of BK_Ca channels in the DRG but not in the spinal cord. Nerve injury primarily reduced the BK_Ca channel immunoreactivity in small‐ and medium‐sized DRG neurons. Furthermore, although the BK_Ca channel immunoreactivity was decreased in the lateral dorsal horn, there was an increase in the BK_Ca channel immunoreactivity present on dorsal horn neurons near the dorsal root entry zone. Blocking the BK_Ca channel with iberiotoxin at the spinal level significantly reduced the mechanical nociceptive withdrawal threshold in control and nerve‐injured rats. Intrathecal injection of the BK_Ca channel opener [1,3‐dihydro‐1‐[2‐hydroxy‐5‐(trifluoromethyl)phenyl]‐5‐(trifluoromethyl)‐2H‐benzimidazol‐2‐one] dose dependently reversed allodynia and hyperalgesia in nerve‐ligated rats but it had no significant effect on nociception in control rats. Our study provides novel information that nerve injury suppresses BK_Ca channel expression in the DRG and induces a redistribution of BK_Ca channels in the spinal dorsal horn. BK_Ca channels are increasingly involved in the control of sensory input in neuropathic pain and may represent a new target for neuropathic pain treatment.     

Projection of cervical dorsal root fibers to the medulla oblongata in the brush-tailed possum, Trichosurus vulpecula

This study describes the projection of cervical spinal afferent nerve fibers to the medulla in the brush-tailed possum, a marsupial mammal. After single dorsal roots (between C2 and T1) were cut in a series of animals, the Fink-Heimer method was used to demonstrate the projection fields of fibers entering the CNS via specific dorsal roots. In the high cervical spinal cord, afferent fibers from each dorsal root form a discrete layer in the dorsal funiculus. The flattened laminae from upper cervical levels are lateral and those from lower cervical levels are medial within the dorsal columns. All afferent fibers at this level are separated from gray matter by the corticospinal fibers in the dorsal funiculus. All cervical roots project throughout most of the length of the well-developed main cuneate nucleus in a loosely segmentotopic fashion. Fibers from rostral roots enter more lateral parts of the nucleus, and fibers from lower levels pass to more medial areas; but terminal projection fields are typically large and overlap extensively. At more rostral medullary levels, fibers from all cervical dorsal roots also reach the external cuneate nucleus. The spatial arrangement here is more complex and more extensively overlapped than in the cuneate nucleus. Rostral cervical root fibers reach ventral and ventrolateral areas of the external cuneate nucleus and continue to its rostral pole; more caudal root fibers project to more dorsal and medial regions within the nucleus. These results demonstrate that projection patterns of spinal afferents in this marsupial are similar to those seen in the few placental species for which detailed data concerning this system are available.     

Areal Distributions of Cortical Neurons Projecting to Different Levels of the Caudal Brain Stem and Spinal Cord in Rats

Distributions of corticospinal and corticobulbar neurons were revealed by tetramethylbenzidine (TMB) processing after injections of wheatgerm agglutinin conjugated to horseradish peroxidase (WGA:HRP) into the cervical or lumbar enlargements of the spinal cord, or medullary or pontine levels of the brain stem. Sections reacted for cytochrome oxidase (CO) allowed patterns of labeled neurons to be related to the details of the body surface map in the first somatosensory cortical area (SI). The results indicate that a number of cortical areas project to these subcortical levels: (1) Projection neurons in granular SI formed a clear somatotopic pattern. The hindpaw region projected to the lumbar enlargement, the forepaw region to the cervical enlargement, the whisker pad field to the lower medulla, and the more rostral face region to more rostral brain stem levels. (2) Each zone of labeled neurons in SI extended into adjacent dysgranular somatosensory cortex, forming a second somatotopic pattern of projection neurons. (3) A somatotopic pattern of projection neurons in primary motor cortex (MI) paralleled SI in mediolateral sequence corresponding to the hindlimb, forelimb, and face. (4) A weak somatotopic pattern of projection neurons was suggested in medial agranular cortex (Ag_m), indicating a premotor field with a rostromedial-to-caudolateral representation of hindlimb, forelimb, and face. (5) A somatotopic pattern of projection neurons representing the foot to face in a mediolateral sequence was observed in medial parietal cortex (PM) located between SI and area 17. (6) In the second somatosensory cortical area (SII), neurons projecting to the brain stem were immediately adjacent caudolaterally to the barrel field of SI, whereas neurons projecting to the upper spinal cord were more lateral. No projection neurons in this region were labeled by the injections in the lower spinal cord. (7) Other foci of projection neurons for the face and forelimb were located rostral to SII, providing evidence for a parietal ventral area (PV) in perirhinal cortex (PR) lateral to SI, and in cortex between SII and PM. None of these regions, which may be higher-order somatosensory areas, contained labeled neurons after injections in the lower spinal cord. Thus, more cortical fields directly influence brain stem and spinal cord levels related to sensory and motor functions of the face and forepaw than the hindlimb.

The termination patterns of corticospinal and corticobulbar projections were studied in other rats with injections of WGA:HRP in SI. Injections in lateral SI representing the face produced dense terminal label in the contralateral trigeminal complex. Injections in cortex devoted to the forelimb and forepaw labeled the contralateral cuneate nucleus and parts of the dorsal horn of the spinal cord. The cortical injections also demonstrated interconnections of parts of SI with some of the other regions of cortex with projections to the spinal cord, and provided further evidence for the existence of PV in rats.     

Dynamics of the transganglionic movement of horseradish peroxidase in primary sensory neurons

Summary The dynamics of horseradish peroxidase (HRP) transport in primary sensory neurons were studied in rats by demonstration of the reaction product in spinal nerves, spinal ganglia, dorsal roots and in the spinal cord at different survival times after application of the enzyme to the transected sciatic nerve and to the spinal cord. Using tetramethylbenzidine as the chromogen according to Mesulam (1978), transganglionic transport of HRP was shown in both the disto-proximal direction after peripheral application, and proximo-distal direction after central application. Significant differences in staining intensity between the central and peripheral processes of primary sensory neurons were found after all survival times used in this study. After peripheral application the number of labeled axons and the staining intensity were higher in spinal nerves than in dorsal roots; an inverse situation occurred after central application. These differences as well as the time sequences in staining of different parts of primary sensory neurons suggest that HRP applied to a peripheral nerve and to the spinal cord, respectively, enters the perikarya of spinal ganglion cells in any case before continuing its movement in a cellulifugal direction. Lysosomal degradation of the major portion of the applied HRP is supposed. However, in the post-perikaryal portion of a considerable number of neurons HRP-transport still occurs to a varying extent, thus resulting in labeling of nerve endings. In some neurons a post-perikaryal transport could not be detected light microscopically. The transport rates differ: the calculated transport rate of disto-proximal, cellulipetal movement in the fastest transporting neurons was 7.5 mm/h, that of the disto-proximal cellulifugal movement 2.5 to 3 mm/h.This work was partly supported by the Hartmann Müller-Stiftung I want to thank Miss Regula Eichholzer for the technical assistance     

Time Course of Immediate Early Gene Protein Expression in the Spinal Cord following Conditioning Stimulation of the Sciatic Nerve in Rats

Long-term potentiation induced by conditioning electrical stimulation of afferent fibers is a widely studied form of synaptic plasticity in the brain and the spinal cord. In the spinal cord dorsal horn, long-term potentiation is induced by a series of high-frequency trains applied to primary afferent fibers. Conditioning stimulation (CS) of sciatic nerve primary afferent fibers also induces expression of immediate early gene proteins in the lumbar spinal cord. However, the time course of immediate early gene expression and the rostral-caudal distribution of expression in the spinal cord have not been systematically studied. Here, we examined the effects of sciatic nerve conditioning stimulation (10 stimulus trains, 0.5 ms stimuli, 7.2 mA, 100 Hz, train duration 2 s, 8 s intervals between trains) on cellular expression of immediate early genes, Arc, c-Fos and Zif268, in anesthetized rats. Immunohistochemical analysis was performed on sagittal sections obtained from Th13- L5 segments of the spinal cord at 1, 2, 3, 6 and 12 h post-CS. Strikingly, all immediate early genes exhibited a monophasic increase in expression with peak increases detected in dorsal horn neurons at 2 hours post-CS. Regional analysis showed peak increases at the location between the L3 and L4 spinal segments. Both Arc, c-Fos and Zif268 remained significantly elevated at 2 hours, followed by a sharp decrease in immediate early gene expression between 2 and 3 hours post-CS. Colocalization analysis performed at 2 hours post-CS showed that all c-Fos and Zif268 neurons were positive for Arc, while 30% and 43% of Arc positive neurons were positive for c-Fos and Zif268, respectively. The present study identifies the spinal cord level and time course of immediate early gene (IEGP) expression of relevance for analysis of IEGPs function in neuronal plasticity and nociception.     

Three-Dimensional Distribution of Sensory Stimulation-Evoked Neuronal Activity of Spinal Dorsal Horn Neurons Analyzed by In Vivo Calcium Imaging

The spinal dorsal horn comprises heterogeneous populations of interneurons and projection neurons, which form neuronal circuits crucial for processing of primary sensory information. Although electrophysiological analyses have uncovered sensory stimulation-evoked neuronal activity of various spinal dorsal horn neurons, monitoring these activities from large ensembles of neurons is needed to obtain a comprehensive view of the spinal dorsal horn circuitry. In the present study, we established in vivo calcium imaging of multiple spinal dorsal horn neurons by using a two-photon microscope and extracted three-dimensional neuronal activity maps of these neurons in response to cutaneous sensory stimulation. For calcium imaging, a fluorescence resonance energy transfer (FRET)-based calcium indicator protein, Yellow Cameleon, which is insensitive to motion artifacts of living animals was introduced into spinal dorsal horn neurons by in utero electroporation. In vivo calcium imaging following pinch, brush, and heat stimulation suggests that laminar distribution of sensory stimulation-evoked neuronal activity in the spinal dorsal horn largely corresponds to that of primary afferent inputs. In addition, cutaneous pinch stimulation elicited activities of neurons in the spinal cord at least until 2 spinal segments away from the central projection field of primary sensory neurons responsible for the stimulated skin point. These results provide a clue to understand neuronal processing of sensory information in the spinal dorsal horn.     

Locomotor Dysfunction and Pain: The Scylla and Charybdis of Fiber Sprouting After Spinal Cord Injury

Injury to the spinal cord (SCI) can produce a constellation of problems including chronic pain, autonomic dysreflexia, and motor dysfunction. Neuroplasticity in the form of fiber sprouting or the lack thereof is an important phenomenon that can contribute to the deleterious effects of SCI. Aberrant sprouting of primary afferent fibers and synaptogenesis within incorrect dorsal horn laminae leads to the development and maintenance of chronic pain as well as autonomic dysreflexia. At the same time, interruption of connections between supraspinal motor control centers and spinal cord output cells, due to lack of successful regenerative sprouting of injured descending fiber tracts, contributes to motor deficits. Similarities in the molecular control of axonal growth of motor and sensory fibers have made the development of cogent therapies difficult. In this study, we discuss recent findings related to the degradation of inhibitory barriers and promotion of sprouting of motor fibers as a strategy for the restoration of motor function and note that this may induce primary afferent fiber sprouting that can contribute to chronic pain. We highlight the importance of careful attentiveness to off-target molecular- and circuit-level modulation of nociceptive processing while moving forward with the development of therapies that will restore motor function after SCI.     

低温保存许旺细胞对周围神经再生的作用

目的：比较原代培养许旺细胞（Schwann cells,SCs)和冷冻保存的SCs移植对损伤后坐骨神经再生的作用。方法：原代培养和液氮保存的SCs分别移植到桥接缺损坐骨神经的硅胶管内。在移植后不同时间（第6和8周末）,硅胶管远端神经干内注射HRP,逆行追踪背根神经节和脊髓前角的标记神经元数量;测量再生神经纤维的复合动作电位传导速度;电镜观察再生神经纤维的髓鞘形成。结果：原代培养和冷冻保存SCs在移植后不同时间其背根神经节和脊髓前角神经元HRP标记细胞数量、再生神经纤维的复合动作电位传导速度基本一致,再生神经纤维髓鞘的形成未见明显差别。结论：冷冻保存的SCs仍具有促进损伤后周围神经再生的能力。     

Effects of tractotomy on reflex activity in the lumbar segment of the rat spinal cord previously disrupted by severing the sciatic nerve

Evoked electrical discharges in the spinal cord roots and dorsal surface ipsilateral to the previously severed sciatic nerve (as well as on the contralateral side) were investigated in rats one, three, seven, and 14 days after tractotomy. Monosynaptic reflex discharges in the ventral roots were found to return to 20–40% of the level of this parameter as measured on the contralateral side within seven and 14 days after tractotomy. Mean amplitude of antidromic dorsal root discharges, afferent peak, and the N₁ component of potential(s) at the dorsal surface ipsilateral to the severed nerve barely altered, remaining significantly lower than on the contralateral side. Mechanisms are suggested for the increase in monosynaptic reflex ventral root discharges ipsilateral to the severed nerve following tractotomy — thought to be largely due to raised sensitivity to transmitter at the motoneuronal membrane resulting from degeneration of synapses of descending pathways.Medical Institute of the Ukrainian Ministry of Health, Dnepropetrovsk. Translated from Neirofiziologiya, Vol. 21, No. 3, pp. 366–371, May–June, 1989.