Dorsal Root Transection Research Articles

Expression of GAP-43 mRNA in the adult mammalian spinal cord under normal conditions and after different types of lesions, with special reference to motoneurons.

In situ hybridization histochemistry was used to detect cell bodies expressing mRNA encoding for the phosphoprotein GAP-43 in the lumbosacral spinal cord of the adult rat, cat and monkey under normal conditions and, in the cat and rat, also after different types of lesions. In the normal spinal cord, a large number of neurons throughout the spinal cord gray matter were found to express GAP-43 mRNA. All neurons, both large and small, in the motor nucleus (Rexed's lamina IX) appeared labeled, indicating that both alpha and gamma motoneurons express GAP-43 mRNA under normal conditions. After axotomy by an incision in the ventral funiculus or a transection of ventral roots or peripheral nerves, GAP-43 mRNA was clearly upregulated in axotomized motoneurons, including both alpha and gamma motoneurons. An increase in GAP-43 mRNA expression was already detectable 24 h postoperatively in lumbar motoneurons both after a transection of the sciatic nerve at knee level and after a transection of ventral roots. At this time, a stronger response was seen in the motoneurons which had been subjected to the distal sciatic nerve transection than was apparent for the more proximal ventral root lesion. An upregulation of GAP-43 mRNA could also be found in intact motoneurons located on the side contralateral to the lesion, but only after a peripheral nerve transection, indicating that the concomitant influence of dorsal root afferents may play a role in GAP-43 mRNA regulation. However, a dorsal root transection alone did not seem to have any detectable influence on the expression of GAP-43 mRNA in spinal motoneurons, while the neurons located in the superficial laminae of the dorsal horn responded with an upregulation of GAP-43 mRNA. The presence of high levels of GAP-43 in neurons has been correlated with periods of axonal growth during both development and regeneration. The role for GAP-43 in neurons under normal conditions is not clear, but it may be linked with events underlying remodelling of synaptic relationships or transmitter release. Our findings provide an anatomical substrate to support such a hypothesis in the normal spinal cord, and indicate a potential role for GAP-43 in axon regeneration of the motoneurons, since GAP-43 mRNA levels was strongly upregulated following both peripheral axotomy and axotomy within the spinal cord.(ABSTRACT TRUNCATED AT 400 WORDS)

Changes of chemoarchitectural organization of the rat spinal cord following ventral and dorsal root transection.

Time-related changes in the distribution of chemical messengers in the rat spinal cord following the transection of dorsal and ventral roots were observed by using immunohistochemistry for the following antigens: microtubule-associated protein 2 (MAP2), calcitonin gene-related peptide (CGRP), substance P (SP), galanin (Gal), Met-enkephalin (Enk), neuropeptide Y (NPY), and serotonin (5-HT). To investigate dendrocytoarchitectonic organizational changes, morphometric analyses were performed on both the gray and the white matter of tissue samples stained with MAP2 antiserum. A significant reduction in the area of gray matter on the lesioned side was seen from 1 to 24 weeks postoperation, and progressive changes in the shape of the gray matter were also observed. CGRP-immunoreactive fibers were reduced in number in the posterior horn after root transection, except in the lateral part of lamina I. In contrast, CGRP immunoreactivity in the anterior horn cells of the ipsilateral side was increased early after transection, but later it progressively decreased. Root transection also caused significant reduction in the number of SP-immunoreactive fibers in the posterior horn, but no changes were seen in the anterior horn. Gal immunoreactivity was also affected by root transection, and it changed in a similar way to CGRP immunoreactivity. 5-HT-immunoreactive fibers were increased in the posterior horn after transection, and later decreased. In the anterior horn, there were no changes in the intensity or distribution pattern of 5-HT-immunoreactive nerve fibers following root transection. Enk and NPY immunoreactivity in the anterior and posterior horns was not affected by root transection up to 24 weeks postoperative. These results show that spinal root transection caused significant changes in the chemoarchitectural organization of nerve fibers containing certain types of chemical messengers, such as CGRP, SP, Gal, and 5-HT, in addition to altering dendritic geometry in the spinal cord.

Properties of the descending limb of the spinobulbospinal micturition reflex pathway in the cat

The micturition reflex is thought to be mediated by a spinobulbospinal reflex pathway passing through the rostral pons. This study examined the properties of the descending limb of the reflex pathway by monitoring the responses of the lower urinary tract to stimulation of the pons in the decerebrate cat. Electrical stimulation (300 μs pulses at 50 Hz intratrain frequencies, 300–500 ms trains, 0.5–15 V) in the region of the locus coeruleus (P 0.5–3.1/L 2–4/H to −2.75) was used to activate the descending excitatory pathway to the sacral parasympathetic nucleus. Low intensity stimulation induced small amplitude, short duration ( 14 ± 11cm H 2O, 10 ± 3s ) bladder contractions in a partially full bladder, whereas higher intensity stimulation induced large amplitude, long duration ( 69 ± 29cm H 2O, 70 ± 44s ) contractions which were similar to distension-induced reflex micturition contractions. The evoked bladder contractions coincided with a reduction in external urethral sphincter (EUS) EMG activity. Following bilateral L 7-S 3 dorsal root transection, electrical stimulation of the pons still elicited the small amplitude bladder contractions, but the larger amplitude, long duration micturition contractions were abolished. During these small evoked bladder contractions, a suppression of EUS activity still occurred following deafferentation, indicating a pontine mediated bladder/EUS synergy. It is concluded that the pons can initiate bladder contractions and coordinated bladder-sphincter activity, but that afferent feedback (via the dorsal roots) is needed to maintain the large amplitude micturition contractions.

The response of nucleus preoticus neurosecretory cells to ovarian pressure in the frog, Rana tigrina

Intraovarian pressure (IOP) of 5, 15, and 25 mm Hg was administered in the frog, Rana tigrina, and the response of the nucleus preopticus (NPO) pars magnocellularis was investigated with aldehyde fuchsin (AF) stain and immunocytochemical method using neurophysin (NP) antisera. The 5 mm Hg IOP treatment resulted in cell and cell nuclear hypertrophy ( P < 0.001); discrete signs of de novo synthesis of AF-positive and NP-immunoreactive material in the perikarya and remarkable increases in the number and size of “Herring bodies” in the processes were observed. Stimulatory response after 15 mm Hg IOP treatment was characterized by dramatic augmentation of the AF-positive and NP-immunoreactive material in the processes; the engorged and coalescing Herring bodies totally predominated the lateral preoptic area. IOP of 25 mm Hg resulted in extensive loss of secretory material; the processes revealed the presence of vacuoles indicative of the rapid anterograde transport of the neurosecretory material. Furthermore, the application of IOP seemed to promote the transport of NP-immunoreactive material toward the anterior preoptic area and amygdala pars medialis and the release of secretory material into the cerebrospinal fluid. No changes were observed in the NPO when treatment was preceded by the transection of ipsilateral dorsal spinal nerve roots or the spinal cord. The results suggest the existence of an afferent neural pathway from the ovary capable of conducting the stretch signals to the NPO and triggering the synthesis and release of neurohypophysial hormones.

Permissive and non‐permissive reactive astrocytes: Immunofluorescence study with antibodies to the glial hyaluronate‐binding protein

Two distinct types of reactive astrocytes were studied in rat CNS. Reactive astrocytes secondary to penetrating trauma (anisomorphic gliosis) were induced by stab wounds to the brain. Reactive astrocytes secondary to Wallerian degeneration (isomorphic gliosis) were induced in spinal cord dorsal columns by dorsal rhizotomy proximal to dorsal root ganglia. Anisomorphic glial scars did not stain with antibodies to the glial hyaluronate-binding protein (GHAP), a structural glycoprotein of white matter extracellular matrix. Conversely, isomorphic glial scars were still GHAP-positive 3 months after dorsal root transection. Only after 5 months did GHAP immunoreactivity start to disappear from the isomorphic glial scar. Extensive dorsal rhizotomy was performed at the lumbar level to produce Wallerian degeneration of spinal cord dorsal columns. One month later, the rats were reoperated and two thoracic dorsal roots were implanted in the degenerated dorsal columns. The rats were examined 1 month after grafting. As expected, there was a dense anisomorphic glial scar at the site of surgery, while the dorsal columns above the graft showed isomorphic gliosis. Extensive axonal growth was observed in the dense glial scar surrounding the graft. Conversely, no axonal growth was observed in the degenerated dorsal columns undergoing isomorphic gliosis above the implant. The findings suggested that GHAP-negative astrocytes responding to traumatic injury are permissive for axonal growth and that GHAP-positive astrocytes responding to Wallerian degeneration are not permissive.

Neurofilament phosphorylation in neuronal perikarya following axotomy: A study of rat spinal cord with ventral and dorsal root transection

Rat spinal cord was stained by indirect immunofluorescence with 11 neurofilament monoclonal antibodies that recognize phosphorylated epitopes. All monoclonals were axon-specific in this location. The large motoneurons containing bundles of neurofilaments did not stain and the pattern remained unchanged after transection of the sciatic nerve in the thigh. With nine monoclonals, stained motoneurons were observed in the ventral horns 3 days, 5 days, 1 week, and 2 weeks after transection of the ventral roots close to the spinal cord. The abnormal motoneurons were typically scattered among normal (i.e., nonstained) cells. Even in animals showing the most severe reaction, the whole motoneuron population at the site of rhizotomy was not affected, stained and nonstained perikarya often coexisting side by side. Stained motoneurons were no longer observed 3 weeks after ventral root transection. Changes in neuronal immunoreactivity were also observed after dorsal root transection. However, a different population was affected, i.e., middle-sized neurons in dorsal horns and at the base of ventral horns. With two monoclonals (A9 and D21), cell bodies remained negative following all operations. It is concluded that axotomy in proximity of the cell body may induce certain neurofilament phosphorylation events in motor neuron perikarya, whereas other phosphorylation events remain confined to the axons under these experimental conditions. The absence of changes after transection of the sciatic nerve in the thigh suggests that neurofilament phosphorylation is a reaction to cell injury rather than a cellular event related to nerve regeneration.

Diaphragm afferent modulation of phrenic motor drive.

Experiments were performed in eight lightly anesthetized thiopental sodium (Pentothal) cats to examine whether diaphragmatic afferents can significantly alter the neural drive to the diaphragm when the animal is exposed to lower body negative pressure. Moving-time-averaged diaphragmatic electromyograms (EMGma) were recorded and compared before and during exposure to lower body negative pressure in each of three consecutive conditions: C7 spinalization, bilateral vagotomy, and cervical dorsal rhizotomy. Application of lower body negative pressure in C7-spinalized animals resulted in a decrease in inspiratory time and peak diaphragmatic activity compared with control levels. After bilateral vagotomy, EMGma activity was prolonged with the application of lower body negative pressure. However, there was no increase in peak EMGma activity. After transection of the cervical dorsal roots subserving the phrenic nerve, the prolongation of diaphragmatic activity negative was eliminated. Therefore, we conclude that the significant increase in duration of inspiration in response to application of lower body negative pressure in the C7-spinalized, bilaterally vagotomized cat is mediated by phrenic nerve afferents.

Carbonic anhydrase activity in the normal and injured peripheral nervous system of the rat

The carbonic anhydrase reactivity of primary neurons and axons of the L4 and L5 lumbar levels was studied in rats before and after various surgical procedures including transection of the spinal cord, removal of dorsal root ganglia, and transection of ventral or dorsal roots or spinal nerves. In normal animals, carbonic anhydrase reactivity was confined to large and medium size neurons of the dorsal root ganglia, and was also present in a sizeable percentage of cells scattered throughout the thoracolumbar sympathetic chain and in the celiac ganglion. At root level, enzymatic staining could be detected in 48.7% of the dorsal root myelinated axons of most sizes, whereas in ventral roots, it was restricted to small myelinated axons, in a proportion much higher at the L4 than in the L5 level. Spinal motoneurons remained unlabeled, despite procedures aimed at increasing the somal concentration of carbonic anhydrase, such as ventral root ligation and blocking of the fast or slow axoplasmic transport using colchicine or iminodiproprionitrile. However, it is likely that reactive ventral root axons originate from neurons situated segmentally in the spinal cord, and do not constitute aberrant sensory fibers, as carbonic anhydrase activity remained unchanged in the L4 and L5 ventral roots after removal of the corresponding spinal ganglia, whereas it disappeared after damage to the spinal cord at the lumbar level, or at a site distal to a ventral root section. Enzymatic staining of neurons of the dorsal root ganglia was not modified by a dorsal rhizotomy, but showed a marked decrease after transection of the spinal nerve. Retrograde fading of the reaction was also noted proximally to a ventral root section, leading, 1 month later, to the total extinction of histochemically detectable carbonic anhydrase.

Maturation of opioid sensitivity of fetal mouse dorsal root ganglion neuron perikarya in organotypic cultures: Regulation by spinal cord

Opioid agonists selectively decrease the duration of the Ca 2+ component of the action potential recorded from embryonic dorsal root ganglion neurons in dissociated cell cultures. In contrast, no significant alterations in the action potentials generated by adult dorsal root ganglion neurons in vivo were detected during opioid exposure. In the present study, the perikaryal opioid sensitivity of fetal mouse dorsal root ganglion neurons was analyzed during maturation in organotypic explant cultures. To determine whether spinal cord might influence this sensitivity, neuron perikarya were tested in ganglia grown: (a) in isolation; (b) attached to spinal cord explants; and (c) attached to spinal cord, but decentralized by a dorsal root transection in mature explants 1–2 weeks before the tests. After 2–8 weeks in culture, the duration of the Ba 2+-enhanced Ca 2+ component of intracellularly recorded action potentials was measured prior to and during bath exposure to the opioid, [ d-Ala 2, d-Leu 5]enkephalin. Sensitive neurons were characterized by a marked, reversible reduction (averaging about 50%) in the duration of the Ca 2+ component (which was antagonized by naloxone). The fraction of opioid-sensitive neuron perikarya in dorsal root ganglia grown attached to cord explants was significantly lower (48%) than in ganglia grown isolated (78%) or decentralized in vitro (79%). The mean duration of the Ca 2+ component was significantly shorter in ganglion cells which had been grown attached to cord, or subsequently decentralized, compared to cells grown in isolated ganglia (by 24 and 38%, respectively). This difference was even larger in the opioid-insensitive groups. Although opioid-sensitive perikarya in ganglia grown attached to cord had a significantly longer Ba 2+-enhanced Ca 2+ component than that of insensitive neurons, some of the insensitive perikarya in all 3 types of explant paradigms displayed Ca 2+ components which were as prolonged as those of sensitive cells. The results obtained in this study support the hypothesis that the observed decrease in the fraction of opioid-sensitive perikarya during development of fetal mouse dorsal root ganglia is due to regulation by interactions with their central target tissue, the spinal cord. The developmental decrease in the duration of the Ca 2+ component of the action potential of these ganglion cells is also enhanced by the presence of the spinal cord. However, regulation of functional opiate receptors and Ca 2+ component duration of the ganglion cell perikarya appear to be independent processes.

Neurokinin A-like immunoreactivity in rat primary sensory neurons; coexistence with substance P

Rat spinal cord, dorsal root ganglia and skin were investigated employing immunohistochemical technique with specific antisera to neurokinin A and substance P. Neurokinin A-like immunoreactivity was detected in the spinal dorsal horn and skin with a similar distribution pattern as that of substance P-like immunoreactivity. After dorsal root transection a parallel decrease of neurokinin A and substance P-like immunoreactivity was observed in the dorsal horn. Using colchicine pretreatment a population of neurokinin A positive cell bodies was seen in the dorsal root ganglia, and by comparison of consecutive sections of the same cells stained for substance P it was revealed that these neurons also display substance P-like immunoreactivity. However, substance P-, but not neurokinin A-, immunoreactive cells were also observed. It is concluded that neurokinin A- and substance P-like immunoreactivity coexist in a population of rat primary sensory neurons.

Regeneration of transected dorsal root ganglion cell axons into the spinal cord in adult frogs ( Xenopus laevis)

The extent of regeneration of the central axonal processes of dorsal root ganglion cells was determined using anterograde horseradish peroxidase histochemistry at 1–12 weeks after dorsal root transection in adult frogs. At 4, 8 and 12 weeks axons were found to have regenerated across the dorsal root entry zone and into the spinal cord.

The effect of dorsal root transection on the efferent motor pattern in the cat's hindlimb during locomotion.

Mesencephalic cats can walk on a treadmill if the midbrain locomotor region is stimulated. The motor pattern of different hindlimb muscles is similar to that of th intact cat. The present experiments in the mesencephalic preparation test if the complex motor pattern in one hindlimb is causally dependent on the afferent signals arising in the same limb during walking. The electromyographical activity and the movement pattern during locomotion were compared before and after transecting all dorsal root fibres originating from one hindlimb. Flexor and extensor muscles at different joints may retain their general pattern after the dorsal root transection. This applies also to muscles such as the knee flexors, which have a short and early flexor burst and a second burst during the extension phase, and the short toe dorsiflexor , which has an early burst in the transition between flexor and extensor activity. After the dorsal root transection the pattern of activity may become more variable and it can even break down altogether. The present results demonstrate that the central nervous system devoid of phasic afferent inflow from one hindlimb can produce a complex motor output to this limb rather than a motor pattern degraded to a simple alternation between flexors and extensors.

Plasticity in the nucleus gracilis of the rat

The nucleus gracilis of the rat contains a somatotopic map of the hindquarter similar to that in other mammals. Acute deafferentation of this dorsal column nucleus (DCN) either by dorsal root transection (roots L4, 5, and 6), by transection of the spinal cord at L3, or by peripheral nerve transection (the sciatic and saphenous nerves) creates as expected a clearly demarcated region in which cells have no receptive fields (RFs). Plasticity in the nucleus gracilis after four types of chronic deafferentiation was investigated: Experiment 1—15 to 20 days after transection of L4, 5, and 6 dorsal roots, cells in the acutely unresponsive region were found to be excited from nearby intact afferent fibers. This expansion of the effective input of intact afferent fibers is known to occur in the spinal cord. Experiment 2—Chronic transection of the sciatic and saphenous nerves was not followed by expansion of the intact input although this does occur in the spinal cord. Experiment 3—Neonatal treatment with capsaicin which destroys unmyelinated afferent fibers produced adult animals with somatotopically organized nucleus gracilis but with cells which exhibited very large RFs. This enlargement is also known to occur in the spinal cord. Experiment 4—Local application of capsaicin to a sciatic nerve of an adult enlarged the RFs of spinal cord cells after some days but had no effect on the functional organization of nucleus gracilis. Expansion of the RF of nucleus gracilis cells was, therefore, seen after dorsal root transection and after neonatal application of capsaicin but not after peripheral nerve transection or application of capsaicin to the adult single nerve. All four maneuvers produced RF expansion in the spinal cord. We conclude that the DCN has a more limited ability to respond to deafferentation than the spinal cord, and suggested that the former lacks a mechanism of connectivity control. The results are consistent with the hypothesis that primary afferent C fibers which innervate the spinal cord but not the DCN, play a role in the formation and stability of RFs formed by A fibers in adult animals.

Characteristics of spinal dorsal horn neurons after partial chronic deafferentation by dorsal root transection

Unilateral transections of 1–3 lumbar dorsal roots were performed in 13 adult cats to investigate the effect of partial deafferentation on dorsal horn neurons. Eleven to 45 days after deafferentation various parameters of spontaneous and evoked activity of 169 neurons were measured and compared to the data of 168 neurons from previous experiments recorded under identical experimental conditions except that these animals had not been deafferented. Eighty-six of the units encountered were located in the segment of transected dorsal root(s) and 82 in the caudally adjacent segment. No significant differences could be observed in the functional properties of these two samples of units. Most parameters measured indicate that either no change at all in responsiveness or signs of decreased excitability occurred in the partially deafferented neurons compared to units recorded in control animals. Discharges evoked by noxious skin heating indicate a linear relationship between discharge frequency and skin temperature. This kind of encoding curve could also be measured during a reversible cold block of the spinal cord at segment L1. The mean encoding curves before and during spinal blockade were not different in deafferented compared to corresponding curves measured in control animals. The only finding that could be interpreted as an indication for increased excitability of partially deafferented neurons was that the mean frequency of spontaneous discharges of a subsample of heat-sensitive neurons was higher in deafferented compared to control animals. Possible mechanisms are discussed.

Ultrastructure of normal and degenerating glomerular terminals of dorsal root axons in the substantia gelatinosa of the rhesus monkey.

The fine structure of primary sensory terminals within glomerular complexes of lamina II of Rexed (substantia gelatinosa Rolandi) in the spinal cord was investigated in normal adult rhesus monkeys and in monkeys subjected to thoracic or lumbosacral dorsal root transection. Three types of "scalloped" primary sensory terminals were distinguished on the basis of their ultrastructural characteristics, size, and distribution of synaptic vesicle population: (1) dense sinusoid axon (DSA) terminals contain medium-sized (42--46 nm and 58--62 nm) and large (80 nm) clear synaptic vesicles; (2) large dense-core vesicles (LDCV) terminals are equipped with empty synaptic vesicles ranging from 30 to 106 nm, large, (80 nm) and very large, (100 nm) dense-core vesicles; and (3) regular synaptic vesicles (RSV) terminals contain a homogeneous population of 45--50 nm clear synaptic vesicles. Following transection of the dorsal roots, all three types of primary afferents degenerate and become engulfed and phagocytosed by glial cells. However, each type of terminal displays a different mode and tempo of degeneration as seen in monkeys sacrificed 36, 48, and 72 hours following rhizotomy. DSAs follow the osmiophilic degeneration pattern; LDCVs are characterized by a gradual increase in the number of "electron-dense bodies" and, less frequently, by a progressive osmiophilic process; RSVs exhibit signs of a filamentous degeneration, accompanied by clusters of synaptic vesicles. The three types of terminals are distributed in an overlapping but distinct pattern within the posterior horn. Thus DSAs are present in highest numbers in lamina II where they constitute the most frequent terminal type. LDCVs also occur in lamina II in its outer half but are most concentrated in lamina I. RSVs predominate in the deeper layers of the dorsal horn (lamina III) but are also found in the internal half of lamina II. On the basis of these ultrastructural data and a comparison with afferent profiles impregnated according to the Golgi method, it appears that DSAs and LDCVs correspond respectively to superficial and marginal collaterals of small, thin dorsal root fibers whereas RSVs represent terminals of deep collaterals from large, thick dorsal root axons.

Mechanosensitive neurons in the spinal cord of the lamprey

‘Fictive locomotion’ in the lamprey in vitro spinal cord-notochord preparation can be entrained by side to side movements of the spinal cord-notochord which mimic swimming movements even after transection of dorsal and ventral roots. This study provides direct evidence of mechonosensitive neurons intrinsic to the spinal cord. Neurons with axons located in the lateral aspect of the spinal cord discharge in response to moderate bending movements of the spinal cord. Movements of this amplitude will inevitably occur during normal swimming.

The role of cervical afferent nerve fiber inhibition of the crossed phrenic phenomenon

High cervical spinal cord hemisection produces a permanent paralysis of the ipsilateral hemidiaphragm. In many species, function is restored to this paretic hemidiaphragm if the contralateral hemidiaphragm is paralyzed by transecting the phrenic nerve. This response is termed the “crossed phrenic phenomenon.” The present study determines the long-term effects on diaphragmatic function after anesthetization or crushing the contralateral phrenic nerve, or after cutting its dorsal roots in rats subjected to a high cervical spinal cord hemisection. Dorsal root transection was the only procedure which resulted in a partial functional recovery of the hemidiaphragm paralyzed by the spinal cord hemisection without a loss of function in the contralateral hemidiaphragm. The results suggest that afferent nerve fibers in the contralateral phrenic nerve may normally inhibit the functional expression of the crossed phrenic pathway, although the precise mechanism for this inhibition is not yet known.

Recovery of function in dorsal horn following partial deafferentation.

1. Collateral sprouting of L6 dorsal root afferents within the dorsal horn of the L6 spinal cord segment has been shown anatomically to occur following transection of all other lumbosacral dorsal roots in the cat. The present study was performed to examine a possible physiological correlate of that sprouting, namely, an altered somatotopic organization of the dorsal horn at L6. This was evaluated by microelectrode mapping of the L6 dorsal horn in normal cats and in cats with L6 spared, lumbosacral dorsal rhizotomies performed 2 days (subacute spared root) or more than 8 wk (chronic spared root), prior to recording. 2. In normal cats the mediolateral somatotopic sequence of hindlimb representation in the L6 dorsal horn is ventral digits 2 and 3, dorsal digits 2 and 3, dorsal foot, rostral and lateral ankle, lateral leg, lateral thigh, and back. In both subacute and chronic spared-root cats the somatotopic sequence is similar to that of normal cats, but there is a loss of proximal thigh and back representation. This proximal body region is represented at the lateral edge of the dorsal horn in normal animals. 3. There was a partial loss of responsiveness of cells in the dorsal horn in the subacute spared-root group and a partial recovery of responsiveness in the chronic group. In the subacute group punctures exhibiting no responses to tactile input tended to be clustered in the lateral dorsal horn. 4. The lateral one-fourth of the dorsal horn in each animal was analyzed in terms of the percentage of recording loci occurring within it. The percentages of recording loci having receptive fields proximal to, distal to, and spanning the middle of the thigh (proximal, distal, and intermediate RFs) were tabulated for each animal. Subacute animals had a significantly lower-than-normal overall percentage of responsive loci in the lateral dorsal horn, but chronic animals did not. The percentage of distal fields therein was not different for the normal versus the subacute group, signifying that the loss of proximal and intermediate fields was responsible for the difference in overall percentage. Chronic animals, however, had significantly more distal fields than did normals. When all fields having any distal component were compared (i.e., distal and intermediate), the difference between the chronic and normal groups did not reach significance. One possible explanation of these findings is that loci having both proximal and distal RF components are unresponsive 2 days after partial denervation, but recover responsiveness to their spared distal input over an 8-wk period. One possible mechanism mediating these changes is localized sprouting of intact, spared axons. Other mechanisms of functional recovery, such as interneuronal sprouting, denervation supersensitivity, and unmasking of latent synapses, are discussed in relation to these and other data.

Initiation and time course of mitosis of non-neuronal cells after spinal motoneuron axotomy

The mitotic response of non-neuronal cells following motor axon transection was measured after in vitro incorporation of [ 3H]thymidine in frog spinal cord. This predominantly ipsilateral response occurs more rapidly and is of greater magnitude when motor axons are unilaterally transected at the ventral root than after sciatic nerve transection. No increase in incorporation occurred when regenerating fibers were transected a second time before reinnervation, but an increase was observed when the second operation was performed after the formation of functional neuromuscular connections had taken place. Autoradiographic studies after dorsal or ventral root transection showed that the distribution of labeled cells approximated the anatomical extent of the injured cellular elements within the spinal cord. These data are discussed in relation to the characteristics of the dividings cells and the nature of the events eliciting mitosis.

Self-mutilation after dorsal rhizotomy in rats: Effects of prior pain and pattern of root lesions

Self-mutilation of a forelimb often occurs in rats after the dorsal roots from the limb are transected. The present study investigated some of the conditions that affect the onset of chewing of the paw. It was found that painful irritation of the forepaw for 1 h prior to root transection significantly accelerated the onset of chewing and shifted the site of origin of chewing to the more distal portions of the paw. This observation suggests that the painful irritation triggers central neural activity characteristic of normal pain processing, and that deafferentation interrupts the input to brain stem inhibitory regions which would ordinarily suppress the pain-related activity. This “pain memory” may thus continue unchecked, thereby accelerating the onset of the abnormal central neural activity which triggers biting or chewing responses. The surprising observation that painful irritation of the paw after rhizotomy also accelerated the onset of chewing suggests that nonneural factors may contribute to the abnormal neural activity that underlies self-mutilation. The effects of different configurations of dorsal root transection on self-mutilation are described and discussed.