Motor denervation induces altered muscle fibre type densities and atrophy in a rat model of neuropathic pain

Loose ligation of a sciatic nerve in rats (chronic constriction injury; CCI) provokes sensory, autonomic, and motor disturbances like those observed in humans with partial peripheral nerve injury. So far, it is unknown whether these motor disturbances result from (mechanical) allodynia or from damage to the motor neuron. These considerations prompted us to assess, in CCI rats, the density of motor axons in both the ligated sciatic nerve and the ipsilateral femoral nerve. To this end, we determined the number of cholinesterase positive fibres. It has been demonstrated previously that muscle fibre type density may be used as a measure of motor denervation and/or hypokinesia. Therefore, the myofibrillar ATPase reaction was employed to assess fibre type density in biopsies obtained from the lateral gastrocnemius muscle (innervated by sciatic nerve) and rectus femoris muscle (innervated by femoral nerve). We observed axonal degeneration of motor fibres within the loosely ligated sciatic nerve, both at an intermediate (day 21) and at a late stage (day 90) after nerve injury. The reduction in the number of motor nerve fibres was more pronounced distal to the site of the ligatures than proximal. A (less pronounced) reduction of motor fibres was observed in the ipsilateral (non-ligated) femoral nerve. In line with these findings, we observed altered fibre type densities in muscle tissue innervated by the ligated sciatic nerve as well as the non-ligated femoral nerve indicative of motor denervation rather than hypokinesia. The findings of this study suggest that the motor disorder induced by partial nerve injury involves degeneration of motor nerve fibres not only within the primarily affected nerve but also within adjacent large peripheral nerves. This spread outside the territory of the primarily affected nerve suggests degeneration of motor neurons at the level of the central nervous system.     

Peripheral nerve repair in the hand with and without motor sensory differentiation

To investigate the value of motor sensory differentiated nerve repair, we examined a group of 9 patients with motor sensory differentiated nerve repair and a group of 13 patients without motor sensory differentiated nerve repair. The clinical and electroneurographic findings were compared. For the clinical examination, Millesi's scoring system was used. The hand function after motor sensory differentiated median nerve repair was 72% +/- 16% compared with 57% +/- 14% without motor sensory differentiation. The hand function after motor sensory differentiated median and ulnar nerve repair was 53% +/- 12% compared with 43% +/- 24% without motor sensory differentiation. After ulnar nerve repair the achieved values for hand function were high even without motor sensory differentiation. Our results indicate that intraoperative motor sensory differentiation of injured nerves is helpful to reestablish particularly the sensory function in median nerve injuries.     

Gains and losses of the XII-VII component of the "baby-sitter" procedure: a morphometric analysis

The classic hypoglossal transfer to the facial nerve is invariably followed by complications caused by tongue atrophy. In 1984, Terzis introduced the "baby-sitter" procedure which involved a formal cross-facial procedure, in addition to partial neurectomy of the hypoglossal nerve, and an end-to-side coaptation with the ipsilateral facial nerve. This reported study provides, for the first time, quantification of the number of hypoglossal motor fibers needed to successfully restore eye sphincter function, using an end-to-side coaptation with preservation of the tongue. Thirty adult Sprague-Dawley rats were divided into six groups: control, denervated, perineurial window, 20 percent partial neurectomy (PN), 40 percent PN, and 80 percent PN. The procedure involves interposing a nerve graft (saphenous) between the partially severed XII nerve and the upper zygomatic branch of the facial nerve. Evaluation of the behavioral data (blink reflex) revealed good-to-superb return of the blinking mechanism in the 40 percent group, without significant tongue atrophy. Electrophysiologic data in the 40 percent neurectomy group demonstrated superiority to the other groups. Quantitative axonal morphometry of the coaptation sites and graft, as well as motor end-plates of the orbicularis oculi muscle and tongue showed the 40 percent partial neurectomy group to be the optimal group.     

Ultrastructure of nerve plexus in flatworms. III. The infra-epithelial nervous system

In addition to a submuscular and subepithelial nerve plexus an infra-epithelial nerve-net also occurs in Notoplana acticola. It contains naked nerve cells which lie between the bases of epithelial cells. Individual neurites occur separately or in small tracts. Synapses contain clear spherical vesicles and are polarized. Post-synaptic neurites tend to be flat and ribbon-like. Rhabdite and mucus secreting cells in the epithelium have synapses associated with them. Neurites ending on the rhabdites appear to originate in the subepithelial plexus. The "sensory-free nerve endings" of earlier workers are reinterpreted as being motor terminals on epithelial secretory cells.     

A motor neuron-specific epitope and the low-affinity nerve growth factor receptor display reciprocal patterns of expression during development, axotomy, and regeneration

Somatic motor neurons begin to express the transmitter synthesizing enzyme, choline acetyltransferase (ChAT) and the low-affinity nerve growth factor receptor (NGFR) during embryonic development. However, as motor neurons mature in postnatal life, they lose immunoreactivity for NGFR and acquire a motor neuron-specific epitope that is recognized by the monoclonal antibody, MO-1. The present study was undertaken to examine the effect of nerve injury in adult rats on these three developmentally regulated markers in two populations of somatic motor neurons. Unilateral transection, ligation, or crushing of the sciatic nerve resulted in a loss of MO-1 binding and a concomitant rise in immunoreactivity for NGFR within axotomized motor neurons in lumbar levels of the spinal cord. These changes, detectable within 5 days following nerve injury, are reversed with reinnervation, but persist if reinnervation is prevented by chronic axotomy. Thus, regulation of the expression of NGFR and the MO-1 epitope appears to be critically dependent upon interactions between motor neurons and target muscles. These observations are also consistent with the idea that during regeneration, neurons may revert to a developmentally immature state; in motor neurons, this state is characterized by the presence of NGFRs and the absence of the MO-1 epitope. Transection of the hypoglossal nerve, a purely motor nerve, resulted in a similar loss of MO-1 binding and a selective rise in NGFR immunoreactivity in neurons within the ipsilateral hypoglossal motor nucleus. In addition, immunoreactivity for ChAT was also lost in axotomized hypoglossal motor neurons. In contrast, injury to the sciatic nerve, which bears both sensory and motor axons, did not result in any detectable change in ChAT immunoreactivity in spinal motor neurons.     

Isolation and characterisation of a diverse family of Arabidopsis two and three-fingered C2H2 zinc finger protein genes and cDNAs

The motor nerve transplantation (MNT) technique is used to transfer an intact nerve into a denervated muscle by harvesting a neurovascular pedicle of muscle containing motor endplates from the motor endplate zone of a donor muscle and implanting it into a denervated muscle. Thirty-six adult New Zealand White rabbits underwent reinnervation of the left long peroneal (LP) muscle (fast twitch) with a motor nerve graft from the soleus muscle (slow twitch). The right LP muscle served as a control. Reinnervation was assessed using microstimulatory single-fiber electromyography (SFEMG), alterations in muscle fiber typing and grouping, and isometric response curves. Neurofilament antibody was used for axon staining. The neurofilament studies provided direct evidence of nerve growth from the motor nerve graft into the adjacent denervated muscle. Median motor endplate jitter was 13 microsec preoperatively, and 26 microsec at 2 months, 29.5 microsec at 4 months, and 14 microsec at 6 months postoperatively (p < 0.001). Isometric tetanic tension studies showed a progressive functional recovery in the reinnervated muscle over 6 months. There was no histological evidence of aberrant reinnervation from any source outside the nerve pedicle. Isometric twitch responses and adenosine triphosphatase studies confirmed the conversion of the reinnervated LP muscle to a slow-type muscle. Acetylcholinesterase studies confirmed the presence of functioning motor endplates beneath the insertion of the motor nerve graft. It is concluded that the MNT technique achieves motor reinnervation by growth of new nerve fibers across the pedicle graft into the recipient muscle.     

Electrophysiologic mapping and cadaveric dissection of the lateral foot: implications for tibial motor nerve conduction studies

OBJECTIVE: To clarify, through electrophysiologic mapping and cadaveric dissection of the lateral foot, the previously published "proximal" and "distal" recording sites for tibial motor nerve conduction studies. DESIGN: Observational. SETTING: Electromyography laboratory; anatomy laboratory. PATIENTS OR OTHER PARTICIPANTS: Ten asymptomatic feet; eight cadaveric feet. MAIN OUTCOME MEASURES: (1) Amplitudes and onset latencies of compound muscle action potentials (CMAPs) recorded over a grid on the lateral foot that included the "proximal" and "distal" recording sites; (2) nerve supply and anatomic boundaries of the abductor digiti minimi pedis (ADMP) and nearby muscles, particularly as they relate to the above recording sites. RESULTS: (1) Relatively large CMAPs were recorded at and around the "proximal" and "distal" sites, with significantly shorter "proximal" latencies. (2) In all cadaveric feet, ADMP was innervated by only the inferior calcaneal nerve (ICN) and was located deep to the "proximal" site, with virtually no muscle fibers deep to the "distal" site. The flexor digiti minimi brevis (FDMB) was conspicuously located immediately deep to the "distal" site and was innervated by only the lateral plantar nerve (LPN). CONCLUSIONS: This study strongly suggests that the "proximal" site records predominantly from the ICN-innervated ADMP, whereas the "distal" site predominantly records from the LPN-innervated FDMB.     

Selective reinnervation of regenerating mixed nerve fibres across a silicone tube gap. Further experimental evidence of neurotropism

This study investigated specific regeneration of a mixed motor and sensory nerve by the method of spinal dorsal root ganglions resection. A 10 mm segment of tibial nerve was resected and the nerve ends inserted in a silicone tube. Fourteen weeks later, dorsal root ganglia from L6 to S1 were resected on the experiment side. Twenty weeks later, the regenerating motor nerve fibres of mixed nerves selectively grew into motor branches. The rate of misdirected growth in mixed nerves was less than 6%. These results suggest that regenerating motor and sensory axons of mixed nerves are able to select their distal target organs accurately. Better results may be obtained using the entubulation repair method.     

Motor fibers in the sural nerve of humans

Although motor fibers in the sural nerve were already described in three individuals, this nerve is considered purely sensory. We investigated the occurrence of motor fibers in 331 sural nerves of 207 individuals. We found motor fibers in 15 nerves (4.5%) or in 13 individuals (6.2%). The identification of motor fibers in the sural nerve before nerve biopsy has important implications for the interpretation of pathologic findings.     

Contributions of pathway and neuron to preferential motor reinnervation

Motor axons regenerating after transection of mixed nerve preferentially reinnervate distal muscle branches, a process termed preferential motor reinnervation (PMR). Motor axon collaterals appear to enter both cutaneous and muscle Schwann cell tubes on a random basis. Double-labeling studies suggest that PMR is generated by pruning collaterals from cutaneous pathways while maintaining those in motor pathways (the "pruning hypothesis"). If all collaterals projecting to muscle are saved, then stimulation of regenerative sprouting should increase specificity by increasing the number of motoneurons with at least one collateral in a muscle pathway. In the current experiments, collateral sprouting is stimulated by crushing the nerve proximal to the repair site before suture, a maneuver that also conditions the neuron and predegenerates the distal pathway. Control experiments are performed to separate these effects from those of collateral generation. Experiments were performed on the rat femoral nerve and evaluated by exposing its terminal cutaneous and muscle branches to HRP or Fluoro-Gold. Crush proximal to the repair site increased motor axon collaterals at least fivefold and significantly increased the percentage of correctly projecting motoneurons, consistent with the pruning hypothesis. Conditioning the nerve with distal crushes before repair had no effect on specificity. A graft model was used to separate the effects of collateral generation and distal stump predegeneration. Previous crush of the proximal femoral nerve significantly increased the specificity of fresh graft reinnervation. Stimulation of regenerative collateral sprouting thus increased PMR, confirming the pruning hypothesis. However, this effect was overshadowed by the dramatic specificity with which predegenerated grafts were reinnervated by fresh uncrushed proximal axons. These unexpected effects of predegeneration on specificity could involve a variety of possible mechanisms and warrant further study because of their mechanistic and clinical implications.     

Coupling Between "Hand" Primary Sensorimotor Cortex and Lower Limb Muscles After Ulnar Nerve Surgical Transfer in Paraplegia.

Previous neuroimaging evidence revealed an "invasion" of "hand" over "lower limb" primary sensorimotor cortex in paraplegic subjects, with the exception of a rare patient who received a surgical motor reinnervation of hip-thigh muscles by the ulnar nerve. Here, the authors show that a functional reorganization of cortico-muscular and cortico-cortical oscillatory coupling was related to the recovery of the rare patient, as a paradigmatic case of long-term plasticity in human sensorimotor cortex after motor reinnervation of paraplegic muscles. This conclusion was based on electroencephalographic and electromyographic data collected while the patient and normal control subjects performed isometric muscle contraction of the left hand or lower limb. Cortico-muscular and cortico-cortical coupling was estimated by electroencephalographic-electromyographic coherence and directed transfer function of a multivariate autoregressive model. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Organization and development of facial motor neurons in the kreisler mutant mouse

The adult facial nerve contains the axons from two populations of efferent neurons. First, the branchiomotor efferent neurons that innervate the muscles of the second arch. These neurons project out of the hindbrain in the motor root and form the facial motor nuclei. Second, the preganglionic efferent neurons that innervate the submandibular and pterygopalatine ganglia. These neurons project from the hindbrain via the intermediate nerve and form the superior salivatory nucleus. The motor neurons of the facial nerve are known to originate within rhombomeres 4 and 5. In the kreisler mouse mutant there is a specific disruption of the hindbrain rhombomeres 5 and 6 appear to be absent. To investigate changes in the organization of the facial motor neurons in this mutant, we have used lipophilic dyes to trace the facial motor components both retrogradely and anterogradely. As expected, facial motor neurons are missing from rhombomere 5 in this mutant. In addition, the loss of these neurons correlates with the specific loss of the superior salivatory nucleus. In contrast, the branchiomeric neurons, that originate in rhombomere 4, appear to develop normally. This includes the caudal migration of their cell bodies forming the genu of the facial nerve. Our studies confirm that rhombomeres are critical to hindbrain development and that they are the fundamental unit at which motor neurons are specified.     

The nucleus is the target for radiation-induced chromosomal instability

Laparoscopic mapping of the phrenic nerve motor points using test stimulation was conducted for the implant of epimysial electrodes for diaphragm pacing in dogs. Both visual assessment of muscle activation and measurements of recruitment were useful for identifying an implant location resulting in a mean electrode placement approximately 14 mm from the phrenic nerve motor points in 16 dogs. Postmortem analysis of the stimulus test site locations and corresponding recruitment curves suggested that the phrenic nerve motor points could be predicted during the laparoscopic procedure to within 4.5 mm of the anatomical motor point.     

The high-affinity sulphonylurea receptor regulates KATP channels in nerve terminals of the rat motor cortex

The coexpression of sulphonylurea binding sites and ATP-sensitive K+(KATP) channels was examined in the rat motor cortex, an area of the CNS exhibiting a high density of sulphonylurea binding. These channels were not detected on neuronal cell bodies, but sulphonylurea-sensitive KATP channels and charybdotoxin-sensitive, large-conductance calcium-activated K+ BKCa channels were detected by patch clamping of fused nerve terminals from the motor cortex. Subcellular fractionation revealed that high-affinity sulphonylurea binding sites were enriched in the nerve terminal fraction, whereas glibenclamide increased calcium-independent glutamate efflux from isolated nerve terminals. It is concluded that neuronal sulphonylurea receptors and KATP channels are functionally linked in the motor cortex and that they are both selectively expressed in nerve terminals, where the KATP channel may serve to limit glutamate release under conditions of metabolic stress.     

Sindbis virus infection of neonatal mice results in a severe stress response

A free vascularized rectus abdominis muscle graft with a long motor nerve was used for reconstruction of unilateral established facial paralysis in one stage. Regarding the procedure, the pedicle vessels were anastomosed to the recipient vessels in the ipsilateral face, and the motor nerve of the muscle was sutured to the contralateral facial nerve. The advantages of using the rectus abdominis muscle are as follows: (1) the muscle is very thin, not bulky, (2) the muscle can be split easily to reduce the volume, (3) the intercostal nerve is long enough (more than 20 cm) to reach the contralateral facial nerve for suturing, (4) the pedicle vessels are large and long, (5) it is possible to carry out simultaneous operations with two teams, and (6) the donor-site morbidity is minimal. The disadvantages of this method are that complicated surgical dissection is required to obtain a motor nerve and that a postoperative abdominal hernia may occur.     

Peripheral motor and sensory nerve conduction studies in haemodialysis patients. A study of 54 patients

Peripheral motor and sensory nerve conduction velocities were studied prospectively in 54 chronic haemodialysis patients. The most sensitive parameters for the detection of polyneuropathy were the deep peroneal nerve motor conduction velocity, the sural nerve sensory conduction velocity and the H-reflex latency and H-index of the S1 roots. All patients examined were found to present at least one abnormal nerve conduction parameter. In the present study the side of the arteriovenous shunt had no statistically significant effect on the sensory and motor nerve conduction velocities in the upper extremities. There was a significant correlation between H-reflex latency and H-reflex index, and between H-reflex latency and sural nerve sensory conduction velocity.     

Long-term hyperglycemia is related to peripheral nerve changes at a diabetes duration of 4 years. The Wisconsin Diabetes Registry

OBJECTIVE: To examine longitudinal hyperglycemia and peripheral nerve responses in a population-based incident cohort. RESEARCH DESIGN AND METHODS: A sample from an incident cohort of young people was comprehensively followed from diagnosis of IDDM. Participants were invited to submit blood samples three times per year for central testing of GHb. During their 4th year of diabetes, nerve conduction studies were performed on the median sensory and motor, peroneal motor, and sural sensory nerves. Relationships between mean GHb and nerve latencies, velocities, and amplitudes were explored. RESULTS: GHb was positively related to all nerve latencies and negatively related to all nerve velocities. The relationships between mean GHb and nerve conduction latencies and velocities differed by sex for the peroneal nerve latency (beta = 0.17 male subjects, beta = -0.01 female subjects; P < 0.001). Pubertal participants had lower velocities and longer latencies than prepubertal participants (beta = 0.37; P = 0.05 peroneal latency), after adjustment for GHb, height, and extremity temperature. Sensory and motor nerve amplitudes were related to GHb, and these relationships did not differ by sex. CONCLUSIONS: Our study indicates that sustained hyperglycemia is related to functional changes, at the minimum, in peripheral sensory and motor nerve conduction at a diabetes duration of 4 years. Our findings are consistent with a dying-back neuropathy, and there is some suggestion that chronic hyperglycemia may be more detrimental to nerves in male subjects than in female subjects.     

Treatments of leprosy at the Ryukyu University Hospital

The competence of neurons to regenerate depends on their ability to initiate a program of gene expression supporting growth and on the growth-permissive properties of glial cells in the distal stump of the injured nerve. Most studies on intrinsic molecular mechanisms governing peripheral nerve regeneration have focussed on the lesion-induced expression of proteins promoting growth cone motility, neurite extension, and adhesion. However, little is known about the expression of intrinsic chemorepulsive proteins and their receptors, after peripheral nerve injury and during nerve regeneration. Here we report the effect of peripheral nerve injury on the expression of the genes encoding sema III/coll-1 and its receptor neuropilin-1, which are known to be expressed in adult sensory and/or motor neurons. We have shown that peripheral nerve crush or transection results in a decline in sema III/coll-1 mRNA expression in injured spinal and facial motor neurons. This decline was paralleled by an induction in the expression of the growth-associated protein B-50/GAP-43. As sema III/coll-1 returned to normal levels following nerve crush, B-50/GAP-43 returned to precrush levels. Thus, the decline in sema III/coll-1 mRNA coincided with sensory and motor neuron regeneration. A sustained decline in sema III/coll-1 mRNA expression was found when regeneration was blocked by nerve transection and ligation. No changes were observed in neuropilin-1 mRNA levels after injury to sensory and motor neurons, suggesting that regenerating peripheral neurons continue to be sensitive to sema III/coll-1. Therefore we propose that a decreased expression of sema III/coll-1, one of the major ligands for neuropilin-1, during peripheral nerve regeneration is an important molecular event that is part of the adaptive response related to the success of regenerative neurite outgrowth occurring following peripheral nerve injury.     

Motor-unit recruitment in self-reinnervated muscle

1. Recruitment order of motor units in self-reinnervated medial gastrocnemius (MG) muscles was studied in decerebrate cats 16 mo after surgical reunion of the cut MG nerve. Pairs of MG motor units were isolated by dual microelectrode penetration of ventral roots to measure their recruitment sequence during cutaneous reflexes in relation to their physiological properties. 2. Physiological properties of reconstituted motor units appeared normal, as expected. Also normal were the relationships among these properties: twitch and tetanic tension tended to increase with axonal conduction velocity and decrease with twitch contraction time. A small fraction of motor units (10/116) in reinnervated muscles produced either no measurable tension or unusually large amounts of tension compared with controls. This was the only distinct feature of the sample of reconstituted units. 3. In muscles reinnervated after nerve section, stretch was notably ineffective in eliciting reflex contraction of MG muscles or their constituent motor units (only 5/116 units). Incomplete recovery from nerve section was probably the cause of this impairment, because stretch reflexes were readily evoked in adjacent untreated muscles and in one reinnervated MG muscle that was studied 16 mo after nerve crush. In contrast with the ineffectiveness of muscle stretch, sural nerve stimulation succeeded in recruiting 49/116 units, a proportion fairly typical of normal MG muscles. 4. The contractions of the first unit recruited in cutaneous reflexes tended to be slower and less forceful than those of the other unit in a pair. By these measures, recruitment obeyed the size principle. This recruitment order with respect to unit contractile properties was not significantly different (P > 0.05) between untreated and reinnervated muscles but was significantly (P < 0.005) different from random order in both groups. The same recruitment pattern was observed for pairs of motor units sampled from the muscle reinnervated after nerve crush, whether units were recruited by muscle stretch or sural nerve stimulation. 5. The usual tendency for motor units with slower conduction velocity (CV) to be recruited in sural nerve reflexes before those with faster CV was not strong in reinnervated muscles. After nerve section the proportion of units exhibiting the usual recruitment pattern was not significantly different (P > 0.05) from a random pattern for CV. 6. The central finding is that the normal recruitment patterns recover from nerve injury in a muscle that is reinnervated by its original nerve. By contrast, stretch reflexes do not recover well from nerve section, and this deficiency may contribute to motor disability.     

Bisphosphonate therapy of reflex sympathetic dystrophy syndrome

Four cases of post-operative ulnar nerve mononeuropathy are reported. In all the cases a severe sensory and motor loss was strictly limited to ulnar nerve territory. The electrophysiological examination: needle examination, motor and sensory nerve conduction studies and even more somatosensory potential evoked from ulnar nerve after stimulation above elbow allowed to eliminate a lesion at the elbow and to asses the lesion at wrist, arm, axilla or plexus. Full recovery occurred once and partial recovery twice. We considered that these ulnar lesions are neuralgic amyotrophies of Parsonage and Turner according to the epidemiological, clinical, evolutive and electrophysiological data.