Effects of Q-switched Nd:YAG laser irradiation on neural impulse propagation: II. Dorsal roots and peripheral nerves.

We have studied the effects of Q-switched Nd:YAG laser irradiation on transmission of neural impulses in sensory nerve fibers in anesthetized rats and cats. Laser light was applied to dorsal roots (rat, cat) and to the sciatic nerve (rat) at increasing pulse energies ranging from 10 to 100 mJ/pulse for 5 minutes each. Compound action potentials recorded from dorsal roots and the sciatic nerve in response to high intensity electrical stimulation during laser application at increasing pulse energies showed a progressive preferential reduction of the slow late component of the electrically evoked response. Preliminary data from multifilament recordings from dorsal roots in cats demonstrated that conduction in small slow conducting fibers was blocked at lower laser pulse energies than in fibers with faster conduction velocities. These results imply, that laser light might have differential effects on slow versus fast conducting sensory nerve fibers. It is most likely that the preferential effect of laser irradiation on slow conducting fibers is mediated by photothermal mechanisms, since temperature increased substantially during laser application.     

急性神经损伤引起脊髓背角C-纤维诱发电位长时程增强

神经损伤引起神经病性疼痛,表现为持续性痛超敏和痛觉过敏。目前对神经病性疼痛的机制尚缺乏了解。我们以往的工作表明强直电刺激坐骨神经可引起脊髓背角C-纤维诱发电位的长时程增强(long-term potentiation,LTP),该LTP被认为是病理性疼痛的突触模型。本研究的目的在于探讨急性神经损伤是否能在完整动物的脊髓背角诱发出C-纤维诱发电位LTP。在以测试刺激(10～20V,0．5ms)电刺激坐骨神经的同时在脊髓背角用微电极记录C一纤维诱发电位。分别用强直刺激、剪断或夹捏坐骨神经诱导LTP。结果发现：(1)剪断或夹捏坐骨神经都可以诱导脊髓背角C-纤维诱发电位的LTP,该LTP可持续到实验结束(3～9h),在剪断神经前10min用利多卡因局部阻滞坐骨神经则可完全阻断LTP的产生;(2)神经损伤诱导的LTP可被NMDA受体阻断剂AP5所阻断;(3)用单次强直刺激引起LTP后,切断坐骨神经可使LTP的幅度进一步增大,而用多次强直电刺激使LTP饱和后,损伤神经则不能使LTP进一步增大。切断神经引起LTP后,强直电刺激也不能使LTP进一步增大。这些结果表明,急性神经损伤可以诱导脊髓背角C纤维诱发电位LTP,且切断神经能更有效地诱导LTP。该试验进一步支持我们的设想,即脊髓背角C-纤维诱发电位LTP可能在病理性疼痛的形成中起重要作用。     

Mechanical and electrical effects of high-frequency and high-intensity stimulation of muscle

A unique tension response can be obtained by stimulating an isometrically held skeletal muscle or a single muscle fiber by a train of high-frequency pulses (2,000 pps) at higher-than-normal intensity, or by a long DC pulse. It is called the tetanoid response, and it is composed of three well-defined stages. Initially, tension develops rapidly, and mechanical output (Po) reaches about 0.35. Subsequently, this tension is maintained at a nearly steady level for the remainder of stimulation. After stimulation, a final increase of tension takes place. Intracellular electrical recordings show that the initial development of tension is elicited by two or three action potentials generated at the beginning of the stimulation, and that no additional action potentials are generated for the remainder of stimulation. During stimulation, part of the fiber membrane (regarded in cross-section) is depolarized, which generates tension, and part of the membrane is hyperpolarized. With termination of stimulation, a single action potential is elicited via anode-break excitation (ABE) on the hyperpolarized portion of the membrane, which gives rise to the final increase of tension.     

GABA能抑制调制大棕蝠下丘听神经元时间编码模式

大棕幅（Eptesicus fuscus）下丘神经元对重复率为10pps(pulse per second）、30pps的串声刺激均产生跟随反应,但对90pps串声刺激的跟随反应则不尽相同,微电泳bicuculline阻断GABA能抑制作用后,所记录的58个神经元中,有13个（22％）放电率及串声刺激反应模式无;45个（78％）神经元放电率有不同程度的增加。对10pps、30pps串声刺激仍能产生跟随反应,但对90pps串声刺激的跟随反应模式有多种变化。其中：17个（29％）神经元为放电率增加的跟随反应;9个（15％）神经元放电率增加,对前100ms的串刺激产生反应且放电密集,而对随后200ms的串刺激只产生少量的放电;15个（26％）神经元放电率增加,在前几十毫秒范围内有较多的放电反应,后续的反应很弱;4个（7％）神经元只对第一个声刺激产生反应,且放电率增加,随后放电急剧减少。结果提示中脑下丘神经元对听觉信息的时间编码可能具有更复杂的机理。     

High-Frequency Electrical Stimulation Can Be a Complementary Therapy to Promote Nerve Regeneration in Diabetic Rats

The purpose of this study was to evaluate whether 1 mA of percutaneous electrical stimulation (ES) at 0, 2, 20, or 200 Hz augments regeneration between the proximal and distal nerve stumps in streptozotocin diabetic rats. A10-mm gap was made in the diabetic rat sciatic nerve by suturing the stumps into silicone rubber tubes. Normal animals were used as the controls. Starting 1 week after transection, ES was applied between the cathode placed at the distal stump and the anode at the proximal stump every other day for 3 weeks. At 4 weeks after surgery, the normal controls and the groups receiving ES at 20, and 200 Hz had a higher success percentage of regeneration compared to the ES groups at 0 and 2 Hz. In addition, quantitative histology of the successfully regenerated nerves revealed that the groups receiving ES at a higher frequency, especially at 200 Hz, had a more mature structure with more myelinated fibers compared to those in the lower-frequency ES groups. Similarly, electrophysiology in the ES group at 200 Hz showed significantly shorter latency, larger amplitude, larger area of evoked muscle action potentials and faster conduction velocity compared to other groups. Immunohistochemical staining showed that ES at a higher frequency could significantly promote calcitonin gene-related peptide expression in lamina I-II regions in the dorsal horn and recruit a higher number of macrophages in the diabetic distal sciatic nerve. The macrophages were found that they could stimulate the secretion of nerve growth factor, platelet-derived growth factor, and transforming growth factor-β in dissected sciatic nerve segments. The ES at a higher frequency could also increase cutaneous blood flow in the ipsilateral hindpaw to the injury. These results indicated that a high-frequency ES could be necessary to heal severed diabetic peripheral nerve with a long gap to be repaired.     

Spinal cord dorsum potentials recorded in vivo after cold injury to the sural nerve in the rabbit

Evoked potentials were recorded in the spinal cord dorsum of rabbits during and after local cooling or freezing of the sural nerve. The potentials were elicited by stimulation through implanted bipolar electrodes distal and proximal to the site of cooling. Recordings were made with a unipolar electrode implanted dorsally into the epidural space.The first two negative deflections of the evoked field potentials (s- and n-potentials) decreased or disappeared during cooling to temperatures between 12 and 2 °C. Immediately following cooling the potentials were depressed by as much as 40% below that of controls. Gradual recovery of the nerve conduction velocity and of both potentials occurred between postoperative Days 20 and 60. Cooling of the nerve to between +2 and ?2 °C caused a 70–80% decrease in amplitude and the precooling values were not obtained within 90 days' follow-up. Local freezing of the sural nerve to ?45 °C resulted in disappearance of the cord dorsum potentials previously obtained by stimulation of the sural nerve with electrode distal to the site frozen. About 40% decrease occurred when stimulated proximal to the site frozen. A fast amplitude increase took place between days 50 and 100 and a slower increase between days 150 and 450 to values more than twice the preoperative amplitudes. A similar amplitude increase was obtained by stimulation of the nerve proximal to the site frozen.     

Leprosy affects the tibial nerves diffusely from the middle of the thigh to the sole of the foot, including skip lesions

This study investigated where leprosy affects the posterior tibial nerve and whether neurolysis is beneficial. Nine patients with bilateral posterior tibial leprous neuropathy with no sensorimotor recovery were studied. Preoperative sensory-muscle and nerve conduction velocity testing revealed the tarsal tunnel to be the site of a severe lesion in all cases. During surgery, the most proximal site of the nerve lesion was detected by electrically stimulating the spinal roots from the second lumbar nerve to the fourth sacral nerve, evoking efferent mixed nerve compound action potentials that were recorded from the exposed tibial nerve. In all patients, the nerve compound action potentials became normal only proximal to the sciatic nerve bifurcation. Epineuriotomy within these seemingly unaffected segments revealed fibrosis of the interfascicular epineurium. Interfascicular neurolysis was performed on all affected segments. A 2-year follow-up showed an increase in girth of the proximal calf musculature in six of eight patients (the ninth patient had no recordable nerve conduction velocity). It was concluded that (1) leprosy affects the tibial nerves in a scattered way from the sciatic nerve main trunk distally to the exit of the tarsal tunnel; and (2) interfascicular, microsurgical neurolysis is beneficial provided that it is performed on all affected nerve segments.     

Click-evoked responses from the exposed intracranial portion of the eight nerve during vestibular nerve section: bipolar and monopolar recordings

We compare the click-evoked compound action potentials from the exposed intracranial portion of the eight nerve using bipolar and monopolar recording electrodes in patients undergoing vestibular nerve section. It is assumed that a bipolar recording electrode will only record propagated neural activity in the auditory nerve, whereas a monopolar recording electrode may in addition record electrical activity that is conducted passively to the recording site. The results of the present study confirm that the earliest detectable propagated neural activity in the intracranial portion of the auditory nerve occurs with a latency that is close to that of peak II of the brain-stem auditory evoked potentials, and the results also confirm that the late components in the click-evoked compound action potentials that have been demonstrated previously using the monopolar recording technique represent propagated neural activity in the auditory nerve. The results also indicate that the responses that are recorded by a bipolar recording electrode, when the small tips of which are placed on the eight nerve when it is relatively dry, represent only small populations of nerve fibers. Even when an attempt is made to align the two tips of a bipolar electrode with the course of the auditory nerve, this type of electrode may record from different populations of nerve fibers.     

Conduction Properties Distinguish Unmyelinated Sympathetic Efferent Fibers and Unmyelinated Primary Afferent Fibers in the Monkey

Background

Different classes of unmyelinated nerve fibers appear to exhibit distinct conductive properties. We sought a criterion based on conduction properties for distinguishing sympathetic efferents and unmyelinated, primary afferents in peripheral nerves.

Methodology/Principal Findings

In anesthetized monkey, centrifugal or centripetal recordings were made from single unmyelinated nerve fibers in the peroneal or sural nerve, and electrical stimuli were applied to either the sciatic nerve or the cutaneous nerve endings, respectively. In centrifugal recordings, electrical stimulation at the sympathetic chain and dorsal root was used to determine the fiber''s origin. In centrifugal recordings, sympathetic fibers exhibited absolute speeding of conduction to a single pair of electrical stimuli separated by 50 ms; the second action potential was conducted faster (0.61 0.16%) than the first unconditioned action potential. This was never observed in primary afferents. Following 2 Hz stimulation (3 min), activity-dependent slowing of conduction in the sympathetics (8.6 0.5%) was greater than in one afferent group (6.7 0.5%) but substantially less than in a second afferent group (29.4 1.9%). In centripetal recordings, most mechanically-insensitive fibers also exhibited absolute speeding to twin pulse stimulation. The subset that did not show this absolute speeding was responsive to chemical stimuli (histamine, capsaicin) and likely consists of mechanically-insensitive afferents. During repetitive twin pulse stimulation, mechanosensitive afferents developed speeding, and speeding in sympathetic fibers increased.

Conclusions/Significance

The presence of absolute speeding provides a criterion by which sympathetic efferents can be differentiated from primary afferents. The differences in conduction properties between sympathetics and afferents likely reflect differential expression of voltage-sensitive ion channels.     

Changes in fraction of current penetrating an axon as a function of duration of stimulating pulse

Single nerve fibers, from the frog sciatic were mounted on an isolation bridge. Threshold current amplitude vs. pulse duration relationships were determined using (a) transmembrane stimulation and (b) external electrodes. The shape of the strength-duration relationships obtained by means of these two modes of stimulation from the same fiber, were found to be significantly different. Chronaxies varied by up to 50 %. The difference between the two strength-duration relationships was maximal for stimulating pulses of 0·1-0·4 msec. These results are discussed in view of the changes in the fraction of current penetrating the cells at different pulse durations. A computational method providing a correction for the frequency dependency of the fraction of current penetrating C.N.S. and other cells, when stimulated by means of external electrodes is described.     

Stimulation pulse characteristics and electrode configuration determine site of excitation in isolated mammalian skeletal muscle: implications for fatigue.

We examined whether electrical field stimulation with varying characteristics could excite isolated mammalian skeletal muscle through different sites. Supramaximal (20-V, 0.1-ms) pulse stimulation with transverse wire or parallel plate electrodes evoked similar forces in nonfatigued slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles from mice. d-tubocurarine shifted the twitch force-stimulation strength relationship toward higher pulse strengths with both electrode configurations in soleus muscle, suggesting that weaker pulses excite muscle via neuromuscular transmission. With wire stimulation, movement of the recording electrode along the muscle caused a delay between the stimulus artifact and the peak of the action potential, consistent with action potential propagation along the sarcolemma. TTX abolished all contractions evoked with 20-V, 0.1-ms pulses, suggesting that excitation occurred via voltage-dependent Na+ channels and, hence, muscle action potentials. TTX did not prevent force development with > or = 0.4-ms pulses in soleus or 1-ms pulses in EDL muscle. Furthermore, myoplasmic Ca2+ (i.e., the fura 2 ratio) and sarcomere shortening were greater during tetanic stimulation with 2.0-ms than with 0.5-ms pulses in flexor digitorum brevis fibers from rats. TTX prevented all shortening and Ca2+ release with 0.5-ms, but not 2.0-ms, pulses, indicating that longer pulses can directly trigger Ca2+ release. Hence, proper interpretation of mechanistic studies requires precise understanding of how muscles are excited; otherwise, incorrect conclusions can be made. Using this new understanding, we showed that disrupted propagation of action potentials along the surface membrane is a major cause of fatigue in soleus muscle that is focally and continuously stimulated at 125 Hz.     

Evoked Activity in Nerve Trunks of the Rat: 4-Aminopyridine-Induced Modifications

In experiments on rats, we studied 4-aminopyridine (4-AP)-induced modifications of the excitability of peripheral nerve fibers in an efferent trunk, the ventral root (VR), and in a mixed trunk including both afferent and efferent fibers, the sciatic nerve (SN). For this purpose, we examined how 4-AP influenced the parameters of integral action potentials recorded from the VR and SN in three experimental modes. These were: (i) stimulation of the SN and recording of antidromic action potentials from the VR in vivo after systemic injections of 4-AP into the animal, (ii) stimulation of a preparation of the SN dissected from the animal after systemic injection of 4-AP and recording of action potentials from another segment of the same preparation in vitro, and (iii) stimulation of an SN preparation and recording of action potentials from another region of this preparation in vitro, but after direct application of the solution of 4-AP to this preparation. It was found that 4-AP significantly increased the threshold for generation of action potentials and enhanced their amplitude, decreased the duration of action potentials recorded from the VR, and shortened the refractory period following these responses. The drug also significantly increased the amplitude and decreased the duration of action potentials recorded from the SN in vitro after systemic injections of the agent, but the threshold for response generation in this preparation noticeably dropped; the post-response refractory period in this case showed no changes. Modifications of action potentials recorded from the SN in vitro after direct applications of 4-AP were in general similar to the described above. Other examined parameters of action potentials (chronaxia and dynamics of an increase in the amplitude related to intensification of stimulation) showed no significant changes under the influence of 4-AP. We conclude that 4-AP increases the excitability of nerve fibers in the nerve trunks under study, but not to the point where the electrical interaction between excited and nonexcited fibers in the fiber conductors under study (VR and SN) overcomes the threshold.     

The effect of subthreshold prepulses on the recruitment order in a nerve trunk analyzed in a simple and a realistic volume conductor model

 The influence of subthreshold depolarizing prepulses on the threshold current-to-distance and the threshold current-to-diameter relationship of myelinated nerve fibers has been investigated. A nerve fiber model was used in combination with both a simple, homogeneous volume conductor model with a point source and a realistic, inhomogeneous volume conductor model of a monofascicular nerve trunk surrounded by a cuff electrode. The models predict that a subthreshold depolarizing prepulse will desensitize Ranvier nodes of fibers in the vicinity of the cathode and thus cause an increase in the threshold current of a subsequent pulse to activate these fibers. If the increase in threshold current of the excited node is large enough, the excitation will be accompanied by a strong hyperpolarization of adjacent nodes, preventing the propagation of action potentials in these fibers. As fibers close to the electrode are more desensitized by prepulses than more distant ones, it is possible to stimulate distant fibers without stimulating such fibers close to the electrode. Moreover, as larger fibers are more desensitized than smaller ones, smaller fibers have lower threshold currents than larger fibers up to a certain distance from the electrode. The realistic model has provided an additional condition for the application of this method to invert nerve fiber recruitment, i.e., real or virtual anodes should be close to the cathode. When using a cuff electrode for this purpose, in the case of monopolar stimulation the cuff length (determining the position of the virtual anodes) should not exceed twice the internodal length of the fibers to be blocked. Similarly, the distance between cathode and anodes should not exceed the internodal length of these fibers when stimulation is to be applied tripolarly. Received: 15 May 2000 / Accepted in revised form: 9 February 2001     

Transmission of rectal electric waves: is it through circular or longitudinal smooth muscle layers or both?

The rectum possesses electric activity in the form of pacesetter (PPs) and action potentials (APs). In recent studies we suggested that the waves are not initiated by the extrarectal autonomic innervation but might be triggered by a 'rectosigmoid pacemaker' and are transmitted in the rectal wall through the rectal musculature and not the enteric nerve plexus. To investigate whether the rectal waves are transmitted through the circular or longitudinal muscle layer, the rectum of 18 mongrel dogs was exposed under anesthesia through an abdominal incision. Three electrodes were applied to the rectal wall (longitudinal muscle layer) and another 3 electrodes to the circular muscle; the latter was exposed by splitting apart the fibers of the longitudinal muscle. Rectal electric activity and pressure were recorded from the 6 electrodes before and after performing individual myotomy of the rectal longitudinal (9 dogs), circular (9 dogs), and then the whole muscle layers (18 dogs). The myotomy was performed proximal to and between the electrodes. Pacesetter (PPs) and action potentials (APs) were recorded from the 3 electrodes on the longitudinal muscle but no waves were registered from those on the circular muscle. After longitudinal muscle myotomy was performed between electrodes 1 and 2, PPs and APs were recorded from electrode 1 but not 2 and 3 and when performed proximally to electrode 1, no waves were registered. The rectal pressure increased concomitantly with occurrence of APs. Circular muscle myotomy effected no change in the rectal electric activity recorded from the 3 electrodes applied to the longitudinal muscle. In total muscle myotomy, the electric waves were recorded from the electrodes proximal but not distal to the myotomy. We propose that the motile activity of the rectal longitudinal muscle is initiated by the electric activity which appears to be triggered by the rectosigmoid pacemaker, while that of the circular muscle fibers is believed to be initiated by the stretch reflex induced by rectal distension. This concept is evidenced not only by the current findings but also by the histologic structure of the rectal musculature being of the unitary type of smooth muscles.     

Changes in the electrical activity of the rabbit proximal colon in vivo by stimulation of the vagus and splanchnic nerves]

1. Using extracellular electrodes placed on the serosa, we recorded the modifications of the electrical activity of the colonic muslce fibers caused by the stimulation of vagal and splanchnic nerve fibers. 2. Vagal stimulation produces two types of junction potentials: excitatory junction potentials (EJPs) and inhibitory junction potentials (IJPs). The IJPs are elicited by stimulation of vagal fibers which innervate intramural non-adrenergic inhibitory neurons. 3. The conduction velocity of the nerve impulse along the vagal pre-ganglionic fibers is 1.01 m/sec for excitatory fibers and 0.5. m/sec for inhibitory fibers. 4. Splanchnic fiber stimulation causes EJP disappearance, blocking transmission between preganglionic fibers and intramural excitatory neurons, and a decrease in IJP amplitude that most likely indicates a previous hyperpolarization of the smooth muscle. 5. IJP persistence during splanchnic stimulation proves that sympathetic inhibition does not modify the transmission of the vagal influx onto the non-adrenergic inhibitory neurons of the intramural plexuses. 6. Through a comparative study of proximal and distal colonic innervation, we are able to show that there is a similar organization of both regions, that is a double inhibitory innervation: an adrenergic one of a sympathetic origin, and a non adrenergic one of a parasympathetic origin.     

In vivo 3-D distributions of electric fields in pig skin with rectangular pulse electrical current stimulation (RPECS)

We developed stimulating and detecting electrodes. We experimentally examined three dimensional (3-D) distributions of electric fields in living pig skin under and around the stimulating electrodes with the detecting electrodes and rectangular pulsed electrical current stimulation (RPECS). We verified our previous physical assumption, E ≈ I / (A σ_dz), in the skin under the electrode, where E, I, A and σ_dz respectively represent the electric field, the externally imposed peak current, the cross sectional area of the stimulating electrode and the perpendicular conductivity of the skin. Pulses were 30 mA, 140 μs and 128 pulses per second (pps). These parameters were previously used in our laboratory to enhance cutaneous regeneration, in vivo, with RPECS. © 1996 Wiley-Liss, Inc.     

Fatigue in mammalian skeletal muscle stimulated under computer control

Functional electrical stimulation (FES) is used to provideparalyzed human subjects with postural support and a limited range ofmovements. Problems encountered with FES include jerky movements fromtension oscillations during stimulation and rapid muscle fatigue. Inthis paper, we report experiments on anesthetized cats that test a new,computer-controlled method of stimulation of the muscle nerve supply,distributed across several inputs, which reduces these problems. After5 min of continuous, distributed stimulation of the medialgastrocnemius muscle at 6 pulses per second (pps) across 6 channels,tension fell to 55.9 ± 3.9% (SE) of its original value. Incomparison, after 5 min of synchronous stimulation of one muscleportion at 36 pps, tension fell to 11 ± 3.7%. At higherstimulation rates, 10 pps per channel (distributed) and 60 pps(synchronous), the differences in fatigue were even greater. Similarresults were obtained when an intermittent, rather than a continuous,stimulation protocol was used. These findings indicate that distributedstimulation has important advantages over other methods forapplications such as FES.

     

Effects of temperature on a moth auditory receptor

Measurements of the thoracic temperature and recordings of the spike activity of the most sensitive auditory receptor (A1 cell) were made in Empyreuma pugione (Arctiidae, Ctenuchinae). The temperature range tested (19–36 °C) is relevant for the behavior and ecology of this species. Experiments were performed during the hours of maximal flying activity in the wild: sunrise and sunset. The thoracic temperature during rest reflects that of the surrounding air; there is an increase of 3–4 °C immediately after ceasing free flying in the laboratory. The spike activity of the tympanic organ was recorded with a stainless-steelhook electrode placed beneath the tympanic nerve in the mesothorax. The A1 cell activity was studied without acoustic stimulation (spontaneous) and in response to 35-kHz acoustic pulses of 20, 40, or 100 ms duration. At all of these durations A1 cell response to saturating stimulus was analysed, while with 40-ms pulses different stimulus intensities were used (20–90 dB SPL in 10-dB steps). The number of action potentials per pulse, mean spike rate, maximal instantaneous discharge, and latency period depend strongly on air temperature, while the variation coefficients of the interspike intervals during the responses were not temperature dependent and vary non-monotonically with stimulus intensity. During responses to a saturating stimulus, the stimulus duration does not affect the activation energy, calculated from an Arrhenius plot, of different physiological features. Adaptation, studied in the responses to 100-ms pulses, is also temperature dependent. This phenomenon has two components, each of which shows different activation energies, suggesting a different membrane origin. High stimulus intensity (90 dB SPL) significantly affects the activation energy of the action potentials and mean spike rate, while the activation energy, of the maximal instantaneous discharge and latency period do not show this strong dependency. The spontaneous A1 cell spike rate varies with temperature, as does the value of the mode of the relative frequency distribution of the interspike interval. The activation energy of the spike rates measured at A1 cell responses to saturating stimuli is in good agreement with that described in amphibian innerear hair cells. It is suggested that this moth auditory receptor cell also has mechanosensitive protein channels.Abbreviations AP/p action potentials per pulse - AP/s action potentials per second - CI confidence interval - E _a activation energy - ISI interspike interval - SD standard deviation - VC variation coefficient     

Motion control of the ankle joint with a multiple contact nerve cuff electrode: a simulation study

The flat interface nerve electrode (FINE) has demonstrated significant capability for fascicular and subfascicular stimulation selectivity. However, due to the inherent complexity of the neuromuscular skeletal systems and nerve–electrode interface, a trajectory tracking motion control algorithm of musculoskeletal systems for functional electrical stimulation using a multiple contact nerve cuff electrode such as FINE has not yet been developed. In our previous study, a control system was developed for multiple-input multiple-output (MIMO) musculoskeletal systems with little prior knowledge of the system. In this study, more realistic computational ankle/subtalar joint model including a finite element model of the sciatic nerve was developed. The control system was tested to control the motion of ankle/subtalar joint angles by modulating the pulse amplitude of each contact of a FINE placed on the sciatic nerve. The simulation results showed that the control strategy based on the separation of steady state and dynamic properties of the system resulted in small output tracking errors for different reference trajectories such as sinusoidal and filtered random signals. The proposed control method also demonstrated robustness against external disturbances and system parameter variations such as muscle fatigue. These simulation results under various circumstances indicate that it is possible to take advantage of multiple contact nerve electrodes with spatial selectivity for the control of limb motion by peripheral nerve stimulation even with limited individual muscle selectivity. This technology could be useful to restore neural function in patients with paralysis.     

Time Course and Characteristics of the Capacity of Sensory Nerves to Reinnervate Skin Territories outside Their Normal Innervation Zones

Factors involved in the outcome of regeneration of the saphenous nerve after a cut or crush lesion were studied in adult rats with electrophysiological recordings of low-threshold mechanoreceptor activity and plasma extravasation of Evans blue after electrical nerve stimulation that activated C fibers.

In the first series of experiments, saphenous and sciatic nerve section was combined with anastomosis of the transected proximal end of the saphenous nerve to the distal end of the cut tibial nerve. Regeneration of saphenous nerve fibers involved in plasma extravasation and low-threshold mechanoreceptor activity in the glabrous skin was observed 13 weeks after nerve anastomosis. Substance P-, calcitonin gene-related peptide-, and protein gene product 9.5 (PGP-9.5)-immunoreactive (IR) thin epidermal and dermal nerve endings, as well as coarse dermal PGP-9.5-IR nerve fibers and Meissner corpuscles and Merkel cell-neurite-like complexes, were observed in the reinnervated glabrous skin at this time.

In a second series of experiments, the time course of the regeneration of saphenous nerve axons to the permanently sciatic-nerve-denervated foot sole was examined. Saphenous-nerve-induced plasma extravasation and low-threshold mechanoreceptor activity in the saphenous nerve were found in the normal saphenous nerve territory 2, 3, 4, and 6 weeks after sciatic nerve cut combined with saphenous nerve crush in the left hindlimb. Saphenous-nerve-induced plasma extravasation was also present in the glabrous skin normally innervated by the sciatic nerve 3, 4, and 6 weeks after the sciatic cut/saphenous crush lesion. However, no low-threshold mechanoreceptor activity was detected in the saphenous nerve when the glabrous skin area was stimulated.

In a third series of experiments, the fate of the expansion of the saphenous nerve territory after saphenous nerve crush was examined when the crushed sciatic nerve had been allowed to regenerate. Nerve fibers involved in plasma extravasation were observed in the glabrous skin of the hindpaw after saphenous nerve, as well as after tibial nerve, C-fiber stimulation 3, 12, and 43 weeks after the saphenous crush/sciatic crush lesion.

Low-threshold mechanoreceptors from the regenerated saphenous nerve, which primarily innervates hairy skin, seem to be functional in the glabrous skin if the axons are guided by the transected tibial nerve by anastomosis. Furthermore, the results indicate that fibers from the regenerating saphenous nerve that have extended into denervated glabrous skin areas can exist even if sciatic nerve axons are allowed to grow back to their original territory.