Peripheral Nerve Trunks Research Articles

Perspectives on new electrode technology for stimulating peripheral nerves with implantable motor prostheses

The limits of present electrode technology are being reached in current motor prostheses for restoring functional movement in paralyzed people. Improved devices require electrodes and stimulation methods that will activate muscles selectively and independently with less implanted hardware. A practical functional neuromuscular stimulation (FNS) system may need to employ extraneural, intraneural, epimysial, or intramuscular electrodes or a combination of these types. The limitations of current muscle electrodes and the anatomy of peripheral nerve innervation of muscle have pointed to stimulation of peripheral nerve trunks as a promising area for investigation. Attempts to use conventional (extraneural) peripheral nerve electrodes for selective activation of muscles in chronic applications have met with only limited success. Intraneural (intrafascicular) electrodes offer the advantages of greater selectivity and lower power requirements, but these may be offset by the difficulty of inserting delicate electrodes through the collagenous epineurium and perineurium while avoiding unacceptable amounts of trauma. Cuff electrodes require more power than intrafascicular ones but may provide more stable recruitment patterns over time, and the opportunity for retrieval and replacement. >

Mechanical Properties of Peripheral Nerves

Peripheral nerve trunks are viscoelastic tissues with unique mechanical characteristics. Tensile strength, which includes elastic limit and mechanical failure, concerns surgeons. This study shows that measurements of the load necessary to achieve certain elongations on specimens outside the body do not correspond with in situ measurements. The necessary load is influenced by the presence or absence of branches and by the amount of fibrosis. Because of transverse contraction, elongation beyond a certain limit substantially decreases intrafascicular volume, leading to increased intrafascicular pressure. Stress relaxation is effective only if the nerve repair site is maintained under constant tension. Its beneficial effect disappears after 10 minutes if the repaired nerve is returned to a relaxed state. Therefore, tension at the repair site should be minimized.

Neuromuscular stimulation selectivity of multiple-contact nerve cuff electrode arrays.

The feasibility of an electrical stimulation method selectively for activating skeletal muscles innervated by a common peripheral nerve trunk has been investigated. The method utilises 'snugly' fitting nerve cuffs that incorporate an array of 12 electrodes. These electrodes have been tested as four longitudinally aligned tripoles (located 90 degrees apart on the cuff inner surface). In acute experiments on rabbit sciatic nerves, we have found that tripolar stimulation with this implant system is in general highly selective. 'Field steering,' wherein a subthreshold transverse current is used in combination with a longitudinal tripolar current, tends to increase the selectivity of stimulation. On a rabbit sciatic nerve, a combination of adjacent longitudinal tripoles of the 12 electrode array generally yields a stimulation performance similar to that which would be expected if a 24 electrode array is used. This system may find a use in functional neuromuscular stimulation applications which require highly selective control over multiple muscles.

ATP activates cationic and anionic conductances in Schwann cells cultured from dorsal root ganglia of the mouse.

The whole-cell configuration of the patch-clamp technique was used to study membrane responses of mouse Schwann cells in organotypique culture to external application of adenosine 5'-triphosphate (ATP). ATP induced an inward current (IATP) which caused a membrane depolarization. IATP was dose dependent with a Kd of 8.4 mM. ATP analogues had the following relative agonist potency: ATP > ADP approximately alpha-beta methylene ATP. Neither AMP nor adenosine were effective. IATP was reversibly reduced by suramin, a P2 purinoceptor antagonist. Alteration of ionic gradients showed that ATP activated simultaneously cationic (potassium and calcium) and anionic (chloride) conductances. Values of the reversal potentials to ATP suggested the following permeability sequence through the anion channel: SCN- > I- > Br- approximately Cl- > aspartate > isethionate. IATP did not appear to be dependent on intracellular calcium, as inclusion or omission of calcium chelator (BAPTA, 10 mM) in the pipette solution had no effect on IATP. The observed ATP response resembles a P2-mediated response in its kinetics, its relative agonist potency and its blockade by suramin, but differs from known ones by its requirement for high concentrations of ATP and the activation of a cationic as well as an anionic conductance.

Nervus terminalis ganglion of the bonnethead shark (Sphyrna tiburo): Evidence for cholinergic and catecholaminergic influence on two cell types distinguished by peptide immunocytochemistry

The nervus terminalis is a ganglionated vertebrate cranial nerve of unknown function that connects the brain and the peripheral nasal structures. To investigate its function, we have studied nervus terminalis ganglion morphology and physiology in the bonnethead shark (Sphyrna tiburo), where the nerve is particularly prominent. Immunocytochemistry for gonadotropin-releasing hormone (GnRH) and Leu-Pro-Leu-Arg-Phe-NH2 (LPLRFamide) revealed two distinct populations of cells. Both were acetylcholinesterase positive, but LPLR-Famide-immunoreactive cells consistently stained more darkly for acetylcholinesterase activity. Tyrosine hydroxylase immunocytochemistry revealed fibers and terminal-like puncta in the ganglion, primarily in areas containing GnRH-immunoreactive cells. Consistent with the anatomy, in vitro electrophysiological recordings provided evidence for cholinergic and catecholaminergic actions. In extracellular recordings, acetylcholine had a variable effect on baseline ganglion cell activity, whereas norepinephrine consistently reduced activity. Electrical stimulation of the nerve trunks suppressed ganglion activity, as did impulses from the brain in vivo. During electrical suppression, acetylcholine consistently increased activity, and norepinephrine decreased activity. Muscarinic and, to a lesser extent, alpha-adrenergic antagonists both increased activity during the electrical suppression, suggesting involvement of both systems. Intracellular recordings revealed two types of ganglion cells that were distinguishable pharmacologically and physiologically. Some cells were hyperpolarized by cholinergic agonists and unaffected by norepinephrine; these cells did not depolarize with peripheral nerve trunk stimulation. Another group of cells did depolarize with peripheral trunk stimulation; a representative of this group was depolarized by carbachol and hyperpolarized by norepinephrine. These and other data suggest that the bonnethead nervus terminalis ganglion contains at least two cell populations that respond differently to acetylcholine and norepinephrine. The bonnethead nervus terminalis ganglion appears to differ fundamentally from sensory and autonomic ganglia but does share some features with the neural circuits of forebrain GnRH systems.

Nerve regeneration in nerve grafts conditioned by vibration exposure

Regeneration distances were studied in nerves from vibration-exposed limbs. One hind limb of anaesthetized rats was attached to a vibration exciter and exposed to vibration (80 Hz/32 m/s2) for 5 h/day for 2 or 5 days. Seven days after the latest vibration period a 10-mm long nerve graft was taken from the vibrated sciatic nerve and sutured into a corresponding defect in the con-tralateral sciatic nerve and vice versa, thereby creating two different models within the same animal: (i) regeneration from a freshly transected unvibrated nerve into a vibrated graft and (ii) regeneration from a vibrated nerve into a fresh nerve graft (vibrated recipient side). Four, 6 or 8 days postoperatively (p.o.) the distances achieved by the regenerating axons were determined using the pinch reflex test. Two days of vibration did not influence the regeneration, but 5 days of vibration reduced the initial delay period and a slight reduction of regeneration rate was observed. After 5 days of vibration an increased regeneration distance was observed in both models at day 4 p.o. and at day 6 p.o. in vibrated grafts. This study demonstrates that vibration can condition peripheral nerves and this may be caused by local changes in the peripheral nerve trunk and in the neuron itself.

Repeatability of nerve thickness assessment in the clinical examination for leprosy.

The assessment of the thickness of the superficial peripheral nerve trunks to document nerve involvement is an important aspect of clinical examination in case finding for leprosy, and is usually done by trained paramedical workers (PMWs). This assessment is subject to variability and has implications on the outcome of the survey. The present study proposes to quantify this variability. In this study, 242 individuals, consisting of 50 neuritic cases, 143 nonneuritic cases of leprosy and 49 normal controls, selected from the records of the trial of BCG prophylaxis in leprosy in South India, were examined by a doctor and paramedical workers. Repeatability of nerve thickness assessment for ulnar and popliteal nerves between the medical officer (MO) and the PMWs was quantified using Kappa statistics. The Kappa values for repeatability between the MO and the PMWs ranged from 0.45 to 0.54 and 0.52 to 0.69 for ulnar and popliteal nerves, respectively. The implications of the variability in nerve assessment are discussed.

Bradykinin excites tetrodotoxin-resistant primary afferent fibers

Bradykinin is a nonapeptide that plays a central role in the production of pain and inflammation. A horizontal spinal cord slice preparation with attached dorsal root and dorsal root ganglion was used to study the effect of bradykinin on afferent fibers. Intracellular recordings were made from dorsal root ganglion and dorsal horn neurons. Bath application of bradykinin (1 μM) to the dorsal root ganglion compartment produced a depolarization ( 5 ± 0.8mV) and firing of action potentials in eight out of eighteen dorsal root ganglion neurons tested. Simultaneous intracellular recordings from dorsal horn neurons revealed that the application of bradykinin to dorsal root ganglion, peripheral nerve trunk or dorsal root resulted in the synaptic activation of dorsal horn neurons. The depolarizing effect of bradykinin on the dorsal root ganglion neurons and its synaptic excitatory effect on dorsal horn neurons was abolished by pretreatment of the same segment of sensory neurons by a B2 bradykinin receptor antagonist ( d-Arg 0, Hyp 3,β-Thi 5,8, dPhe 7)-bradykinin (5 μM). Bath application of tetrodotoxin (TTX; 0.2–1 μM) to the sensory neurons blocked electrically-evoked action potentials in large dorsal root ganglion neurons and, consequently, excitatory postsynaptic potentials in dorsal horn neurons evoked by electrical activation of low threshold afferent fibers. However, the stimulatory effects, both depolarization and firing of action potentials, of bradykinin were resistant to TTX. Replacement of sodium ions with TRIS completely abolished the stimulatory effect of bradykinin on the sensory neurons. Bradykinin potentiated the postsynaptic potentials induced by electrical stimulation of TTX-resistant afferent fibers. The facilitation of transmission was measured as an increase of 232 ± 32% ( n = 7) in the size (area under the curve) of the TTX-resistant slow excitatory postsynaptic potential and about 180% increase in the number of action potentials fired. Our data suggest the presence of a population of primary afferent fibers that become responsive to electrical stimulation in the presence of bradykinin and these could be responsible for hyperalgesia.

Neonatal guanethidine treatment alters endoneurial but not dorsal root ganglion perfusion in the rat

In previous work, we suggested that there were differences in vasoregulation between dorsal root ganglia (DRG) and the endoneurium of peripheral nerve trunks. To investigate symphatetic control of both microvessel beds, we compared local perfusion in the sciatic nerve endoneurium and lumbar DRG of adult Sprague-Dawley rats treated from neonatal day 5 with guanethidine monosulfate to induce adrenergic sympathectomy. Control rats were injected with normal saline. Local blood flow and microvascular resistance were measured using microelectrodes sensitive to the clearance of hydrogen. Guanethidine-sympathectomized rats had higher sciatic endoneurial blood flow and lower endoneurial microvascular resistance than saline-injected controls. In contrast, DRG blood flow was not increased by sympathectomy and was comparable to control value despite the hypotension induced by sympathectomy. The results that sympathetic control of local blood flow and may be less apparent in DRG than endoneurium and that local autoregulation may protect DRG from hypotension.

The role of the Schwann cell in trophic support and regeneration.

Schwann cells show remarkable versatility in undertaking a broad repertoire of functions. Ensheathment and myelination are specifically regulated by contact with axons, and the Schwann cell is centrally involved in extracellular matrix production in the peripheral nerve trunk. Additional Schwann cell functions include the promotion of both peripheral and central nervous system regeneration, provision of a versatile source of trophic factors, the capacity to remyelinate central nervous system axons, and the restoration of electrophysiological conduction. Since it is now possible to isolate Schwann cells both from neonatal and adult human peripheral nerve, their ability to promote regenerative efforts by many central neurons suggests a role for Schwann cell autografts in influencing central nervous system repair.

Repetitive stimulation induced potentiation of excitatory transmission in the rat dorsal horn: an in vitro study.

1. The effects of repetitive stimulation of primary afferents in lumbar dorsal roots on synaptic transmission in the dorsal horn (DH) were studied in a rat spinal cord slice-dorsal root ganglion (DRG)-peripheral nerve trunk preparation by the use of intracellular recording from neurons (n = 115) of the spinal dorsal horn (depth 147 +/- 139, mean +/- SD). All DH neurons were excited synaptically by electrical stimulation of the dorsal root or the peripheral nerve trunk. The electrical shocks were calibrated to produce activation either of large fibers (10-20 V, 0.02 ms) or the whole fiber population including unmyelinated afferents (supramaximal stimulus: > 35 V, 0.5 ms). Postsynaptic potentials induced by low intensity repetitive stimulation of primary afferents at frequencies below 5 Hz failed to produce a prolonged change in the resting membrane potential. In 97/115 DH neurons, slow excitatory postsynaptic potentials (EPSP)--evoked by high intensity low-frequency repetitive stimulation (0.1-2 Hz) of primary afferents--summated, producing a prolonged cumulative depolarization. In the remaining 18/115 DH neurons, high intensity low-frequency stimulation produced a cumulative hyperpolarizing response. 2. In 22 of 97 neurons that responded to high intensity repetitive stimulation with a cumulative depolarization, wind-up in the firing of action potentials was recorded. In all but two experiments, neurons that responded with wind-up to stimulation of one root responded with wind-up to stimulation of the adjacent dorsal root. In 14/22 wind-up neurons, the synaptic response to high intensity stimulation of primary afferents was composed of a short latency EPSP, followed by an inhibitory postsynaptic potential (IPSP), followed by a slow EPSP. The decrease of the amplitude and duration of the IPSP obtained during train stimulation did not seem to contribute to facilitation of transmission induced by repetitive stimulation. 3. The wind-up in firing of action potentials was followed by a prolonged potentiation of synaptic transmission in tetanized synapses. A test of other, adjacent primary afferents revealed that these synapses in the neurons in the superficial laminae had not undergone potentiation. This "synaptic specificity" of post-wind-up potentiation suggested that the mechanism for the induction of stimulation-dependent changes in the excitability of the DH neuron is presynaptic to the recorded-from neuron. 4. In a concentration of 0.5 microM and higher, tetrodotoxin (TTX) applied to sensory neurons selectively blocked action potentials in large myelinated primary afferents.(ABSTRACT TRUNCATED AT 400 WORDS)

Sumatriptan blocks neurogenic inflammation in the peripheral nerve trunk.

We tested the action of intraperitoneal sumatriptan, a 5-HT1D receptor agonist that aborts migraine headaches, using a model of neurogenic inflammation induced by capsaicin applied to the rat sciatic epineurium. Sumatriptan prevented the development of capsaicin-induced hyperemia without inducing pretreatment vasoconstriction or altering AV shunt flow. The findings indicate that sumatriptan prevents "neurogenic" vasodilation by a mechanism other than vasoconstriction or changes in AV shunt flow.

Electrophysiological analysis of the convergence of peripheral inputs onto neurons of the coeliac ganglion in the guinea pig

The convergence of intestinofugal axons from different intestinal regions onto individual neurons in the coeliac ganglion of the guinea pig was investigated using intracellular recording methods in vitro. Peripheral nerve trunks from the distal ileum, the most proximal colon and the colon near the colonic flexure were electrically stimulated along with preganglionic fibres running in the splanchnic nerve. Fast cholinergic excitatory synaptic potentials (EPSPs) were seen in ganglion cells in response to stimulation of each nerve trunk. Roughly half of 78 neurons impaled received inputs from stimulation of peripheral nerves, and almost all of these received input from the proximal colon. Most cells responded to stimulation of more than one peripheral nerve indicating that coeliac neurons receive converging inputs from intestinofugal neurons located in more than one intestinal region. In a second series of experiments, segments of intestine were left attached to the ganglion and distended with saline to stimulate peripheral mechanosensory input to the coeliac ganglion. In each experiment, two segments were stimulated. A subgroup of ganglion cells exhibited spontaneous fast EPSPs and the frequency of these potentials was increased by distension of one or other of the attached intestinal segments. However, few neurons responded to distension of both of the attached intestinal segments suggesting that some of the intestinofugal inputs to the coeliac ganglion identified by electrical stimulation may be sensitive to sensory modalities other than distension. Hexamethonium (0.5 mM) applied to the intestine, and not to the coeliac ganglion, reduced the frequency of the spontaneous synaptic potentials seen in coeliac ganglion cells, but did not abolish the response to distension of the colon ( n = 8). When the Ca 2+ concentration of the solution bathing the proximal colon was reduced to block all synaptic transmission in the enteric plexuses the background synaptic input was further depressed, but again the response to distension was little changed ( n = 4). This suggests that at least some of the neurons projecting from the colon to the coeliac ganglion are first order mechanosensory neurons.

神経幹切除を要した骨・軟部腫ようの治療

神経幹切除を要した骨・軟部腫ようの治療

Silent neuropathy in leprosy: an epidemiological description.

This paper presents epidemiological data on silent nerve function impairment in leprosy based on a retrospective study of 536 patients registered at Green Pastures Hospital, Pokhara, West Nepal. Because of the multiple possible aetiologies it is proposed that the clinical phenomenon should be named 'Silent Neuropathy' (SN). We defined this as sensory or motor impairment without skin signs of reversal reaction or erythema nodosum leprosum (ENL), without evident nerve tenderness and without spontaneous complaints of nerve pain (burning or shooting pain), paraesthesia or numbness. The functioning of the main peripheral nerve trunks known to be affected in leprosy was assessed using a nylon filament to test touch thresholds and a manual voluntary muscle test to quantify muscle strength. Almost 7% of new patients had SN at first examination. The incidence rate of SN among the 336 new patients who were available for follow-up was 4.1 per 100 person years at risk. In total, 75% of all SN episodes diagnosed after the start of chemotherapy occurred during the first year of treatment. During steroid treatment the sensory and motor function in nerves affected by SN improved significantly (p = 0.012, Wilcoxon matched-pairs signed ranks test) over a period of 3 months. The patients with more extensive clinical disease (3/9 or more body areas involved, more than 3 enlarged nerves or a positive skin smear) were found to be at increased risk of developing SN. We discuss 4 different possible aetiologies of SN: 1, Schwann cell pathology; 2, nerve fibrosis; 3, cell-mediated immune reaction; and 4, intra-neural ENL. Some epidemiological evidence is presented that suggests that SN cannot be equated with a 'reversal reaction expressing itself in the nerves'. It is recommended that all patients should have a nerve function assessment at every visit to the clinic at least during their first year of treatment. Regular nerve function assessment is essential to detect SN at an early stage and to prevent permanent impairment of nerve function.

Extracellular matrix arrangements of rat facial nerve.

The nonneural elements of the peripheral nerve trunk are three different kinds of connective tissue sheath; epineurium, perineurium, and endoneurium. They play a role in protecting the nerve against stretching and compressive forces. The perineurium also forms a permeability barrier. The aim of this study is to observe the three-dimensional architecture of the connective tissue of rat facial nerve, and investigate the components.

Somatosensory evoked potentials (SEPs) elicited by magnetic nerve stimulation

Magnetic stimulation of peripheral nerves at distal and proximal sites of the upper and lower extremities and at the midlumbar level were used to elicit cortical somatosensory evoked potentials. Evidence is provided that peripheral nerve trunks, rather than distal receptor afferents, are the anatomical structures stimulated by the electromagnetic fields. Magnetic stimulation of peripheral nerves is considered to be useful for an evaluation of the integrity of proximal nerves, nerve roots and central conduction along sensory pathways. In contrast to electrical nerve stimulation, magnetic stimulation is painless and can be applied to proximal nerves and plexus. By means of proximal nerve stimulation central sensory conduction can be tested even in patients with peripheral nerve lesions or polyneuropathy.

Expanding roles for the Schwann cell: ensheathment, myelination, trophism and regeneration

Schwann cells show remarkable versatility in undertaking a broad repertoire of functions. It is now clear that the well known functions of ensheathment and myelination are specifically regulated by contact with axons, that the Schwann cell is centrally involved in extracellular matrix production in the peripheral nerve trunk, and that the Schwann cell plays a critical role in promoting axonal regeneration in the peripheral nervous system. The Schwann cell's ability to promote regenerative efforts in many central neurons has led to an increasing interest in using Schwann cell autografts for central nervous system repair.

Close apposition among neighbouring axonal endings in a neuroma.

Axons in intact peripheral nerve trunks constitute independent afferent and efferent communication channels. However, when nerves are severed, several different forms of axon-axon cross-excitation develop in association with the injury site. In this study we have examined experimental sciatic nerve-end neuromas in rats with special interest in the compartmentalization of individual axons, and the barriers that separate close neighbours. At postinjury times at which functional coupling is known to occur, neuromas were found to contain many examples of axons in which adjacent membrane faces come into close contact without an intervening Schwann cell process. These occur in bundles containing from two to as many as 30 individual nerve fibres wrapped in a common Schwann cell sheath. The surface area of close apposition between axon pairs ranges up to several tens of micron2. Closely apposed axon profiles may be outgrowing branches of a single parent axon, but anterograde tracer data indicate that many belong to independent neurons. Closely apposed axons are separated from one another, and from associated Schwann cell processes, by a cleft about 130 A wide. No synapses, gap junctions or tight junctions were observed. Extracellular tracer studies using La3+ and Ruthenium Red indicated that the cleft system is patent, permitting the free diffusion of small molecules between the space adjacent to the axolemma and the bulk extracellular compartment. Together, these data provide a structural basis for interfibre interactions based on local electrical current flow (ephaptic crosstalk), as well as coupling mediated by K+ ions and neurotransmitter molecules.

Diabetes mellitus prevents capsaicin from inducing hyperaemia in the rat sciatic nerve

Loss of neurogenic inflammation in response to tissue injury may be an important complication of diabetes mellitus. We studied local neurogenic inflammation in the peripheral nerve trunk of Sprague-Dawley rats 4 months following the induction of diabetes by streptozotocin injection. To assess neurogenic inflammation, the epineurial plexus of the sciatic nerve was exposed to topical capsaicin, an agent that releases vasoactive neuropeptides from perivascular afferent terminals. Under normal circumstances, local vasodilation results in endoneurial hyperaemia or a 'flare'. We evaluated the influence of capsaicin in diabetic sciatic nerve by making serial measurements of endoneurial blood flow using microelectrodes sensitive to hydrogen clearance. After 4 months of hyperglycaemia (glucose > 16.0 mmol/l), diabetic animals had slowing of unmyelinated and myelinated sural sensory conduction velocity compared to citrate buffer injected controls. Baseline sciatic endoneurial blood flow was unaltered by diabetes, and was comparable to controls. There was an expected hyperaemic response of endoneurial blood flow to capsaicin in control rat sciatic endoneurium but no consistent 'flare' response in diabetic rats. Our findings indicate that there is loss of capsaicin-related neurogenic inflammation in the vasa nervorum of experimental diabetes. It is possible that a similar deficit following nerve injury could impair the milieu for axonal regeneration in diabetes.