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Survey of current experimental studies of effects of traditional chinese medicine on peripheral nerve regeneration.

The repairing and regeneration of peripheral nerves is a very complex biological and cytological process, its mechanism is unclear so far, and thus results in the lack of specific and effectual therapy and medicament. Chinese herbs and their effective components have their own inimitable predominance in promoting peripheral nerve regeneration, such as their multi-factorial, multi-target and multi-functional action, abundant source, inexpensive, etc. In this paper, the experimental studies reported in recent 5 years concerning the effects of Chinese herbs or their active components on peripheral nerve repairing and regeneration are reviewed in respects of the integral level, cellular level, molecular level and gene level.

Animals↗

Nonsurgical management of pain secondary to peripheral nerve injuries.

Physicians and surgeons dealing with peripheral nerve injuries have long been plagued by the chronic intractable pain which often follows these injuries. Early recognition of the associated problems and prompt intervention by a multidisciplinary team approach to the pain is essential. Although the techniques reviewed here were presented as separate choices, the treatment of the patient should employ a combined approach of good surgical repair, positive encouragement, non-addicting medications, appropriately timed nerve blocks, aggressive physical and occupational therapy, and electrical stimulation techniques as the patient's physical recovery permits. The importance of early psychological assessment and intervention in this complex phenomenon cannot be overemphasized. Together these techniques may succeed in reducing the morbidity associated with peripheral nerve injuries.

Anti-Inflammatory Agents, Non-Steroidal↗

Complement receptors in human peripheral nerve tissue.

Cryostat sections of human peripheral nerve tissue adsorbed sheep erythrocytes sensitized with antibody and human complement (EAC). Activated complement was essential for the reaction to occur. The receptor had specificity for the C3b fragment. In order to obrain binding to nerve tissue, the indicator cells had to be coated with more complement than that required for binding to C3b receptors in spleen and renal tissue. The receptors are located within the nerve fascicles and are probably of glycoprotein nature. The receptors for C3b in peripheral nerve tissus may be of significance in the deposition of immune complexes, which may play a role in acute polyradiculoneuritis.

Complement Activation↗

A prospective, randomized, controlled evaluation of peripheral nerve stimulation versus standard clinical dosing of neuromuscular blocking agents in critically ill patients.

OBJECTIVES: To determine if vecuronium doses individualized by peripheral nerve stimulation are lower than those doses chosen by standard clinical techniques; and to determine whether patients monitored by peripheral nerve stimulation exhibit shorter recovery times and less prolonged neuromuscular blockade after discontinuation of vecuronium than control patients. DESIGN: A prospective, randomized, controlled, single-blind trial. SETTING: Two ten-bed medical intensive care units of a 937-bed tertiary care, not-for-profit, teaching hospital and health system. PATIENTS: Mechanically ventilated patients requiring continuous neuromuscular blockade as part of their therapy. INTERVENTIONS: After obtaining written, informed consent and baseline neurologic examinations, patients were randomized to treatment, where dosing was individualized by peripheral nerve stimulation or standard clinical assessment. Doses in the peripheral nerve stimulation group were adjusted to 90% blockade (Train-of-Four of 1/4). The standard clinical dosing group received doses individualized to clinical response by the medical team (blinded to Train-of-Four). Differences between groups were evaluated by Wilcoxon matched-pairs signed rank test. MEASUREMENTS AND MAIN RESULTS: A total of 77 patients (35 standard clinical patients vs. 42 peripheral nerve stimulation patients) were enrolled in the study. Despite no difference in initial doses and time to reach 90% blockade or clinical response between groups, the peripheral nerve stimulation group used less drug than the standard clinical group (0.040 +/- 0.028 vs. 0.070 +/- 0.030 mg/kg/hr, respectively, p = .001). The total cumulative amount of vecuronium for the episode of paralysis was greater in the control group (285.8 +/- 246.6 vs. 137.1 +/- 106.4 mg, p = .001). The peripheral nerve stimulation group recovered neuromuscular function (relative risk of 1.85, with 95% confidence interval [CI] of 1.02-3.35, p = .039) and spontaneous ventilation (relative risk of 1.86, 95% CI 1.00-3.45, p = .047) faster than the control group. In patients, adjusting for renal dysfunction, the likelihood of a faster recovery in the peripheral nerve stimulation group increased for neuromuscular function (relative risk of 1.89, 95% CI of 1.07-3.32, p = .018) and spontaneous ventilation (relative risk of 2.27, 95% CI of 1.23-4.21, p = .019). Patients with combined renal and liver failure similarly demonstrated a faster recovery in the peripheral nerve stimulation group. The recovery was affected to a lesser extent by adjusting for concurrent aminoglycoside and corticosteroid administration. CONCLUSIONS: Use of peripheral nerve stimulation for monitoring the degree of blockade and adjusting drug doses in continuously paralyzed critically ill medical patients results in lower doses of vecuronium to maintain a desired depth of paralysis, and allows a faster recovery of neuromuscular function and spontaneous ventilation.

Adult↗

Expression and glycanation of the NG2 proteoglycan in developing, adult, and damaged peripheral nerve.

We have investigated expression of the axon growth-inhibitory proteoglycan NG2 in peripheral nerve. In the adult, NG2 was present on endoneurial and perineurial fibroblasts, but not on Schwann cells. At birth, peripheral nerve NG2 was heavily glycanated, but was much less so in the adult. In vitro, sciatic nerve fibroblasts also produced heavily glycanated NG2. After peripheral nerve injury in rats and humans, an accumulation of NG2-positive cells was observed at the injury site. In the rat, there was an increase in NG2 glycanation for at least 2 weeks following injury. In mixed cultures of Schwann cells and peripheral nerve fibroblasts, the axons preferred to grow on the Schwann cells and seldom crossed onto the fibroblasts. Three-dimensional cultures of sciatic nerve fibroblasts were inhibitory to the growth of dorsal root ganglion axons. Inhibition of proteoglycan synthesis made the cells more permissive. NG2 may play a part in blocking axon regeneration through scar tissue in injured human peripheral nerve.

Animals↗

Prior collateral sprouting enhances elongation rate of sensory axons regenerating through acellular distal segment of a crushed peripheral nerve.

Regenerating axons in crushed peripheral nerves grow through their distal nerve segments even in the absence of Schwann cell support, but their elongation rate is reduced by 30%. We examined whether prior exposure of sensory neurons to trophic factors achieved either by collateral sprouting or regeneration after conditioning lesion could enhance subsequent regeneration of their axons after crush, and compensate for loss of cell support. Collateral sprouting of the peroneal cutaneous sensory axons in the rat was evoked by transection of adjacent peripheral nerves in the hind leg. The segment of the peroneal nerve distal to the crush was made acellular by repeated freezing. Sensory axon elongation rate during regeneration was measured by the nerve pinch test. Prior axonal sprouting for two weeks increased the elongation rate of sensory axons through the acellular distal nerve segment back to normal value observed in control crushed nerves. The number of axons in the acellular distal segment at a fixed distance from the crush site was about 50% greater in sprouting than in control non-sprouting nerves. However, prior sprouting caused no further increase of axon elongation rate in control crushed nerves. Prior collateral sprouting, therefore, could in some respect compensate for loss of cell support in the distal nerve segment after crush lesion. This suggests that loss of cell-produced trophic factors is probably responsible for slower elongation rate through the acellular distal nerve segment. Surprisingly, prior conditioning lesion caused no enhancement of elongation rate of the sensory axons regenerating in the absence of cell support.

Animals↗

Malignant peripheral nerve sheath tumor of the kidney.

Malignant peripheral nerve sheath tumors are rare in the genitourinary organs, with few reports of occurrence in the kidney. We describe a patient with a renal malignant peripheral nerve sheath tumor, discovered after excision of a malignant peripheral nerve sheath scalp lesion, with additional masses in the lung and shoulder on metastatic evaluation. This patient underwent neoadjuvant intravenous doxorubicin therapy, followed by surgical resection of the scalp, lung and shoulder lesions in addition to a radical nephrectomy.

Aged↗

Peripheral nerve war injuries.

OBJECTIVE: The purpose of this study is to evaluate peripheral nerve war injuries sustained during the war in southern Croatia and Bosnia and Herzegovina. PATIENTS AND METHODS: During the war in Croatia, 713 patients (99% male and 1% female) with wounds inflicted by firearms were examined at the Laboratory of Neurophysiology, University Hospital, Split. The patients, soldiers and civilians alike, ranged in age from 6 to 73 years (average, 28 years). All patients with firearm nerve war injuries underwent detection by electromyography and plurisegmental examination of the damaged peripheral nerve (neurography). The patients were examined and controlled on three occasions: within 2 months after wounding; up to 6 months after wounding; and more than 6 months after wounding. RESULTS: Single peripheral nerve lesions were present in 80% of the patients, and multiple peripheral nerve or plexus lesions were present in 20% of the patients. Peroneal and ulnar nerves were most often involved (20.9% and 19.8%, respectively). Associated massive injuries to the muscles, large blood vessels, or vital organs were present in 45% of the patients. Wounds were inflicted by shell fragments in 80% of the patients and by projectiles in 20% of the patients. CONCLUSION: According to our results, better recovery was achieved with conservative treatment and when physical therapy was initiated early with maximal patient cooperation. Electromyoneurographic findings were the most valid in the prognostic classification of war-inflicted peripheral nerve injuries.

Adolescent↗

Indications for peripheral nerve and brachial plexus surgery.

Management of peripheral nerve injuries differs depending on the mechanism of injury. 1. If a nerve has been sharply and completely transected, it should be acutely repaired, especially if proximally located. 2. If a nerve has been bluntly divided and the stumps are found to be bruised, they should be tacked to adjacent planes. A secondary repair at 2 to 4 weeks is then recommended. 3. With closed injury in which the nerve is most likely still in continuity, the patient should be followed clinically and electrically for 2 to 5 months, depending on the nerve involved and the mechanism of injury. If there is no reversal of the proximal portion of the neurologic deficit by that time, surgical exploration should be done. Use of intraoperative NAP testing is important in this large category of injuries. 4. Injection and electrical injuries to a nerve are two special categories of lesions in continuity and require a highly specialized and individualized treatment dependent on the degree of deficit and severity of pain. 5. Pain unresponsive to medical treatment may also be an indication for surgery on a peripheral nerve, especially if the injured nerve needs to be repaired because of persistent neurologic loss. 6. Management of brachial plexus injuries is somewhat different. Function of each element of the plexus has to be analyzed separately. Several clinical, electrical, and radiologic findings may provide important information about how proximal the lesion is. 7. Missile wounds usually leave the nerve in continuity. Initial management is surgically conservative. Nonetheless, many of these lesions will subsequently require resection based on NAP recordings. 8. Management of obstetric brachial plexus palsy is controversial. We recommend initial conservative management, with observation much longer (9 to 12 months) than for other stretch injuries occurring in adults. With this approach, some but not many of such injuries will still need repair.

Brachial Plexus↗

Resetting voluntary movement using peripheral nerve stimulation: influence of loading conditions and relative effectiveness.

The effect of peripheral nerve stimulation on voluntary rhythmic flexion-extension movements at the wrist was studied in nine normal volunteers, and the results compared with the effect of cortical stimulation on the same task. In the first part of the study, magnetic stimulation was given over the inner aspect of the right arm at levels which, at rest, resulted in a wrist flexion twitch of at least 10 degrees. We were able to confirm that this form of (peripheral-nerve) stimulation is an effective means of phase-resetting voluntary wrist movements. In addition, and unlike magnetic stimulation applied over the contralateral motor cortex, changes in the standing torque load, against which the subjects moved, had little influence on the effectiveness of this form of stimulation. Similarly, the amplitude and direction of the averaged first post-stimulus position peak ("P1"), previously identified as important determinants of the resetting induced by a cortical stimulus, were largely independent of the loading torque. In a second part to the study, we directly compared, for a constant loading torque, the resetting induced by magnetic cortical stimulation with that following magnetic stimulation of peripheral nerves. The relationship between the amplitude of P1 and the associated resetting index was identical for both forms of stimulation. Our observations indicate that magnetic stimulation of peripheral nerves is an effective means of resetting voluntary movement. It differs from magnetic cortical stimulation in that the effects of peripheral nerve stimulation are little altered by changes in loading torque. When differences in the size of P1 are allowed for, both peripheral nerve and cortical stimulation are equally effective means of resetting voluntary rhythmical movement.

Adult↗

The neurone and its response to peripheral nerve compression.

In all types of peripheral nerve injury, it is important to realize that the lesion affects one extended cell, the neurone, which extends from the central nervous system down to the target tissue in the extremity. Compression of a peripheral nerve can disturb the intraneural transport (axonal transport) of a large variety of substances. This may be followed by morphological and biochemical changes in the nerve cell body. These central changes may effect the axon as a whole and confer on the nerve an increased susceptibility to trauma. Studies concerning the reaction of neurones to compression, relevant when discussing the double crush syndrome, are reviewed.

Animals↗

Outcome following implantation of a peripheral nerve stimulator in patients with chronic nerve pain.

This study evaluated the usefulness of the implanted peripheral nerve stimulator in patients with pain following injury to a peripheral nerve. The patient sample (n = 17) consisted of 7 men and 10 women with a mean age of 48 years (SD = 18 years). The mean follow-up time since implantation of the stimulator was 21 months (SD = 15 months). Workers' compensation and/or litigation were involved in 11 cases. Peripheral nerve stimulators were placed in the upper extremity in 12 patients and in the lower extremity in 5 patients. Pain relief following implantation was rated as excellent by five patients, good by six patients, fair by four patients, and poor by two patients. A statistically significant decrease in reported pain level was found postoperatively (p < 0.0003). There was no statistically significant difference in postoperative pain level between men and women (p = 0.30), between cases involving workers' compensation or litigation and those not involving these issues (p = 1.0), or between patients who received an upper-extremity implant and those who received a lower-extremity implant (p = 0.56). Of the 12 patients who were unable to work before the operation, 6 returned to work after the operation. In conclusion, peripheral nerve stimulators can be useful in decreasing pain in carefully selected patients with severe neurogenic pain.

Adolescent↗

Continuous peripheral nerve block for battlefield anesthesia and evacuation.

Peripheral nerve and continuous peripheral nerve block (CPNB) have the potential to be valuable techniques in combat anesthesia. We describe the first successful application of CPNB in the pain management and surgical management of a combat casualty as he was evacuated from the Iraqi battlefield to the United States.

Adult↗

Receptors for NGF and GDNF are highly expressed in human peripheral nerve neuroma.

Immunhistochemistry of 10 traumatic human peripheral nerve neuromas and 5 normal digital nerves revealed a high immunoreactivity for the nerve growth factor (NGF) receptors p75 and trkA and the glial cell line-derived neurotrophic factor (GDNF) receptor GFRalpha-1. Semiquantitative image analysis showed a significantly increased trkA immunoreactivity in the neuroma group. The presence of the receptors may provide a way to influence therapy of peripheral nerve neuroma by administration of neurotrophins or other substances with binding sites similar to those of a neurotrophic factor.

Chronic Disease↗

The microenvironment of injured and regenerating peripheral nerves.

Local events in the milieu of injured peripheral nerve trunks may have an important influence on the likelihood of regenerative success or the development of neuropathic pain. Injury-related changes in the microcirculation of this milieu have provided some evidence that axonal endbulbs, structures that form at the proximal end of transected axons, dump peptides and other molecules into the injury milieu where they may exert local actions, including those on microvessels. During a later phase of nerve repair, macrophage influx and pancellular proliferative events appear to develop in a coordinated fashion. Nitric oxide is probably an important and prominent player in the injured nerve trunk, both at early and later stages of the repair process. A better understanding of the injured peripheral nerve microenvironment may allow therapeutic approaches that can enhance regeneration and diminish pain.

Animals↗

[Morphological changes and electrophysiological study of motor neuron of spinal cord following delayed repair of peripheral nerve injury].

OBJECTIVE: Following the delayed repair of peripheral nerve injury, the cell number of anterior horn of the spinal cord and its ultrastructural changes, motorneuron and its electrophysiological changes were investigated. METHODS: In 16 rabbits the common peroneal nerves of both sides being transected one year later were divided into four groups randomly: the degeneration group and regeneration of 1, 3 and 5 months groups. Another 4 rabbits were used for control. All transected common peroneal nerves underwent epineural suture except for the degeneration group the electrophysiological examination was carried out at 1, 3 and 5 months postoperatively. Retrograde labelling of the anterior horn cells was demonstrated and the cells were observed under light and electronmicroscope. RESULTS: 1. The number of labelled anterior horn cell in the spinal cord was 45% of the normal population after denervation for one year (P < 0.01). The number of labelled cells increased steadily from 48% to 57% and 68% of normal values at 1, 3 and 5 months following delayed nerve repair (P < 0.01). 2. The ultrastructure of the anterior horn cells of the recover gradually after repair. 3. With the progress of regeneration the latency become shortened, the conduction velocity was increased, the amplitude of action potential was increased. CONCLUSION: Following delayed repair of injury of peripheral nerve, the morphology of anterior horn cells of spinal cord and electrophysiological display all revealed evidence of regeneration, thus the late repair of injury of peripheral nerve was valid.

Animals↗

Activation of adenosine and P2Y receptors by ATP in human peripheral nerve.

Receptors for ATP in the peripheral nervous system may contribute to the transduction of sensory, including nociceptive, stimuli and are candidates in the pathogenesis of neuropathic pain. In a complex neural tissue, such as the human peripheral nerve trunk, ATP may activate P2X, P2Y, and adenosine receptors present on various cell types. Experiments were performed on segments of isolated human sural nerves. The experimental set-up enabled simultaneous recording of C fiber excitability, intracellular Ca(2+) ([Ca(2+)](i)) and extracellular K(+) activity (aK(e)). The increase in excitability of unmyelinated fibers seen during bath application of both ATP and adenosine was reversed to a reduction in axonal excitability in the presence of 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolol[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385), an antagonist of adenosine A2 receptors. The pharmacological profile of the axonal subexcitability indicates the presence and activation of adenosine A1 receptors. Intracellular Ca(2+) transients were observed during bath application of ATP but not of adenosine and were blocked by 2'-deoxy- N(6)-methyladenosine 3',5'-bisphosphate (MRS 2179), an antagonist at P2Y(1) receptors. K(+)-sensitive microelectrodes were used to search for a possible activation of P2X receptors by ATP. In isolated rat vagus nerve, activation of P2X receptors by alpha,beta-methylene-adenosine 5'-triphosphate (alpha,beta-meATP) and by diadenosine pentaphosphate (Ap5A) resulted in a rapid, transient rise in the extracellular K(+) activity. In contrast, in human nerve, application of P2X receptor agonists did not result in a detectable elevation of aK(e). The data suggest that ATP-induced changes in axonal excitability and of [Ca(2+)](i) result from activation of adenosine A2, A1 and P2Y nucleotide receptors in human nerve; a contribution of P2X receptors was not found with the methods used. It is suggested that antagonists of A2 receptors might suppress enhanced activity in human nociceptive afferent nerve fibers under conditions in which ATP and/or adenosine is released into the trunk of a human peripheral nerve.

Adenosine Triphosphate↗

Demonstration of Fc gamma receptors on human peripheral nerve fibres.

Cryostat sections of human peripheral nerves adsorbed sheep erythrocytes (E) sensitized with rabbit IgG antibodies (A) (EA). No adsorption occurred using unsensitized E or E sensitized with IgM or F(ab')2 fragments of IgG. The binding of EA was inhibited by IgG and by Fc fragments of IgG, but not by IgA, IgM, F(ab')2 fragments of IgG or albumin, and thus indicated the presence of receptors for the Fc part of IgG (FcR). IgG1 and IgG3 subclasses inhibited the haemadsorption. IgG4 was less inhibitory than IgG1 and IgG3, whereas IgG2 did not inhibit the binding of EA. The receptors were sensitive to periodic acid, formaldehyde and heat. FcR were present in sections of both unmyelinated and myelinated nerves, indicating that the binding was not to myelin. FcR were also demonstrated in sections of fetal peripheral nerves at a gestational age of approximately 21 weeks. Using immune complexes of horseradish peroxidase (HRP) and rabbit IgG antibodies to HRP and a monoclonal antibody against FcR, the receptors were shown on the nerve fibres, probably on the Schwann cell membrane (neurilemma).

Aged↗