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 » Introduction
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 »  the Progress in ...
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Table of Contents    
Year : 2016  |  Volume : 64  |  Issue : 5  |  Page : 880-885

Identification of the sensory and motor fascicles in the peripheral nerve: A historical review and recent progress

1 Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University; Department of Orthopedics, The First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Heilongjiang, People's Republic of China
2 Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Heilongjiang, People's Republic of China
3 Department of Hand Surgery, The First Affiliated Hospital of Jilin University, Changchun, People's Republic of China

Date of Web Publication12-Sep-2016

Correspondence Address:
Bi Zhenggang
Department of Orthopedics, The First Affiliated Hospital, Harbin Medical University, Youzheng Street, Harbin, Heilongjiang 150001
People's Republic of China
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.190241

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 » Abstract 

The aim of the study was to critically review the clinical approach to distinguish the sensory and motor nerve fascicles of the peripheral nerve system and to explore potential novel techniques to meet the clinical needs. The principles and shortcomings of the currently used methods for identification of sensory and motor nerve fascicles, including nerve morphology, electrical stimulation, spectroscopy, enzymohistochemistry staining (acetylcholinesterase [AchE], carbonic anhydrase [CA] and choline acetyltransferase [ChAC] histochemistry staining methods), and immunochemical staining were systematically reviewed. The progress in diffusion tensor imaging, proteomic approaches, and quantum dots (QDs) assessment in clinical applications to identify sensory or motor fascicles has been discussed. Traditional methods such as physical and enzymohistochemical methods are not suitable for the precise differentiation of sensory and motor nerve fascicles. Immunohistochemical staining using AchE, CA, and ChAC is promising in differentiation of sensory and motor nerve fascicles. Diffusion tensor imaging can reflect morphological details of nerve fibers. Proteomics can reveal the dynamics of specific proteins discriminating sensory and motor fascicles. QDs, with their size-dependent optical properties, make them the ideal protein markers for identification of the sensory or motor nerves. Diffusion tensor imaging, proteomics and QDs-imaging will facilitate the clinical identification of motor and sensory nerve fascicles, help in improving surgical success rates and assist in postoperative functional recovery.

Keywords: Diffusion tensor imaging; peripheral nerve; proteomics; sensory-motor fascicles

How to cite this article:
Xianyu M, Zhenggang B, Laijin L. Identification of the sensory and motor fascicles in the peripheral nerve: A historical review and recent progress. Neurol India 2016;64:880-5

How to cite this URL:
Xianyu M, Zhenggang B, Laijin L. Identification of the sensory and motor fascicles in the peripheral nerve: A historical review and recent progress. Neurol India [serial online] 2016 [cited 2019 Nov 21];64:880-5. Available from:

 » Introduction Top

Peripheral nerve injury often results in a significant functional impairment although microsurgical repair techniques permit an accurate nerve alignment during surgery. Differentiated nerve fascicle repair can maximize the functional recovery. No technique till date, however, can rapidly and accurately distinguish between the motor and sensory nerve fascicles during surgery.[1] Surgeons mostly rely on estimating the properties of both stumps of the damaged peripheral nerve fascicles according to their experience and perform the interfascicular repair within a limited surgical field. In addition, misalignment could cause partial or total loss of nerve function. Therefore, it is important to correctly identify peripheral nerve fascicles, allowing surgeons to perform fascicular repair accurately, thus facilitating the recovery of peripheral nerve functions.[2]

Three major questions exist while attempting to identify peripheral motor and sensory nerve fascicles: (i) What are the major improvements in clinical methods? (ii) Are there any specific markers?, and (iii) Can quantum dots (QDs) be utilized to label motor or sensory fascicles? Significant improvements in the clinical techniques will be obtained by not only further refinements in the microsurgical techniques but also better understanding of cellular and molecular biology of peripheral nerve fascicles and the application of QDs in molecular fluorescence labeling. This review, therefore, focuses on the recent progress and future perspectives in differentiating between motor and sensory nerve fascicles in clinical practice.

 » Physical Methods to Identify the Peripheral Nerve Fascicles Top

Various physical methods such as electrophysiological methods and spectroscopy have been investigated for fascicle identification. Hakstian firstly identified the nerve fascicles by stimulating the dissected fascicles in the distal and proximal stumps.[3] Gual et al., performed the initial clinical trial using electrical stimulus to identify and align sensory and motor nerves.[4] Turkof et al., conducted experiments with sheep ulnar nerves and concluded that central motor-evoked potentials could be utilized to distinguish sensory from motor nerve fascicles.[5] However, this method cannot be used on intact nerve trunks, in situ. Electrophysiological methods require local anesthesia and are not precise enough to be effective during surgery. The infrared spectrum method [6] and Raman spectrum method [7],[8] cannot be applied easily during surgery owing to the extensive equipment required, the complicated calculations that need to be done, and many other interference factors that are involved.

 » Enzymohistochemistry Staining Methods for Identifying the Peripheral Nerve Fascicles Top

Enzymohistochemistry staining has long been employed by surgeons for the identification of nerve fascicles. The activity of carbonic anhydrase (CA) is found to be higher in sensory fascicles than that in motor fascicles.[9],[10] It can, therefore, be used as a biomarker for different nerve fascicles. Acetylcholinesterase (AchE), on the contrary, has been found to be significantly higher in motor fascicles than in sensory fascicles.[11],[12],[13],[14],[15] The level of choline acetyltransferase (ChAC) in motor fascicles is 8 times higher than that in sensory fascicles.[16],[17] The first practical method that helps to differentiate nerve fascicles based on the measurement of CA activity was reported by Engel et al.[16] Freilinger et al., achieved the differentiation of sensory fascicles from motor fascicles by AchE staining within 4 h.[12] The newer method developed by Ganel et al., has shortened this detection time to about 70–80 min.[17],[18] The histochemical method based on Karnovsky's stain or CA activity can be completed within 1 h, making it effective during surgeries.[13], 14, [19],[20],[21] However, the effectiveness of the nerve fascicle identification methods based on the measurement of CA, AchE, and ChAC activity is very limited as these procedures require significant time for incubation. In addition, these methods are not sensitive enough to be used in the cases with old peripheral nerve injuries where enzymatic activities are significantly reduced in the distal nerve stumps due to  Wallerian degeneration More Details.

 » Immunohistochemical Staining for Identifying the Peripheral Nerve Fascicles Top

The inability to find a specific marker in fresh or dated peripheral nerve injuries largely impedes the successful identification of nerve fascicles. It is of great importance, therefore, to find specific biomarkers to differentiate the motor and sensory nerve fascicles. Recent studies have highlighted the critical role played by specific proteins in forming peripheral nerve fascicles. Protein electrophoresis has shown that the 35 KD sensory neuronal-specific protein (SSP-35), isolated and purified from rat spinal ganglia and sensory fibers, is present in the spinal sensory ganglia, but not in the spinal motor neurons.[22] By combining trypsin digest and liquid chromatography ion trap mass spectrometry, SSP-35 was identified as annexin V by Shen et al.[23] Godfrey et al., isolated a 95/150-KD doublet glycoprotein on the basis of its capability to induce the aggregation of acetylcholine receptors on cultured myotubes from the synaptic basal lamina of the torpedo electric organ and identified it as agrin.[24],[25] Subsequently, they suggested that agrin-like molecules were secreted from motor neurons in the chicken nervous system.[26],[27] Another protein released from the axons of cultured chicken embryonic dorsal root ganglion neurons was identified as axonin-1,[28] which was later demonstrated to be prevalent in nerve fiber tracts.[29] Recent studies using annexin V and agrin as specific markers for sensory and motor nerve fascicles, respectively, have shown their potential clinical utility.[30],[31] The detailed roles of these proteins on peripheral nerve fascicle identification, however, remain largely unknown. A comparison of these methods is listed in [Table 1].
Table 1: Comparison of the available methods in identifying sensory and motor fascicles in peripheral nerves

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 » the Progress in Screening for Peripheral Nerve Fascicle-Specific Proteins Using Proteomic Methods Top

The inherent complexity of the peripheral nerve system suggests that the identification of motor and sensory fascicles cannot be reliably dependent on any single protein marker. A proteomic study is of great value in discovering novel biomarkers. Proteomics achieves a comprehensive and quantitative description of protein expression profiles under the biological influence, such as developmental events and environmental stress.[32] High-throughput, rapid, and precise proteomic techniques have been used for screening clinically relevant biomarkers.[33] Seven proteins are expressed primarily in the dorsal root ganglia. This has been determined by comparing axonal proteins from the dorsal root ganglia with proteins from the ventral horn of the spinal cord using two-dimensional gel electrophoresis.[34] Using proteomics, Jiménez et al., examined the temporal expression pattern of proteins in rat sciatic nerves after experimental crush and came to the conclusion that peripheral nerve regeneration is a complex and dynamic process.[35] Therefore, dynamic observations should also be useful in identifying the specific proteins of sensory or motor nerve fascicles, making proteomics a novel way of protein identification (instead of the classical methods that attempt to identify a single protein at a single time point). So far, no systematic studies that attempt to classify proteins that are helpful in the differentiation of motor and sensory fascicles have been performed at a proteome scale. However, it is believed that motor and sensory fascicles in peripheral nerves have unique proteomic profiles.[36] Comparing the profiles of normal sensory and motor fascicles to those of recently injured fascicles could lead to the demarcation of specific proteins that may further help in the identification of motor and sensory fascicles, which are recently injured, from those that were injured in the past.

 » Morphology-Based Identification of the Peripheral Nerve Fascicles Top

There have been appreciable efforts devoted to developing morphological methods for differentiating between motor and sensory nerve fascicles. The topography of various nerves at different levels as well as intraoperative sketches of the fascicular pattern offer limited help to surgeons as demonstrated by Sunderland [37] and Zhong et al.[38] The cross sections of proximal and distal stumps of an injured nerve fail to show mirror images and differ in their appearances. Past studies of microsurgical techniques meticulously described the nature of peripheral nerves and stated that differentiating the nerve function fascicles was difficult. Nerve morphology alone, therefore, cannot effectively help to identify nerve fascicles based on the traditional imaging techniques. The diffusion tensor imaging technique, however, could be developed as a novel noninvasive method for differentiating motor and sensory nerves. The first clinical trial attempting to detect the sciatic nerve with magnetic resonance (MR) diffusion tensor imaging generated satisfactory results.[39] Recently, this technique has been tested by the observation of peripheral nerves in patients with chronic inflammatory demyelinating polyradiculoneuropathy,[40] carpal tunnel syndrome,[41] and peripheral nerve tumors or tumor-like conditions.[42] Besides, diffusion tensor imaging has also been used to assess the condition of peripheral nerve regeneration [43] and proximal nerve integrity.[44] Diffusion tensor imaging can offer information beyond the routine clinical MR imaging [45] and thus has a potential role in the diagnosis and treatment of nerve disease. Its role in differentiating between motor and sensory nerve fascicles, therefore, is worth further investigations.

 » Progress Achieved in the Clinical Molecular Fluorescence Labeling Technique Using Quantum Dots Top

Currently, increasing interest has been focused on the technique of molecular fluorescence labeling using QDs, which is a potentially feasible labeling method to differentiate between motor and sensory fascicles of the peripheral nerve. QDs are usually described as “artificial atoms” that possess unique optical properties, such as size and composition-tunable wavelengths of fluorescent emission, extremely large absorption cross sections in a wide spectral range, narrow fluorescence emission spectra, high photoluminescence quantum yields, and an extremely good photo stability, when compared with the conventional fluorophores.[46] QDs can circumvent some of the limitations of the biochemical organic dyes, and their size-dependent optical properties make them the ideal candidates for tunable absorbers and emitters in biological fluorescent labeling.[47],[48],[49],[50] Bruchez et al.,[45] first reported the use of CdSe/ZnS and CdSe/CdS nano-crystals to stain F-actin in fixed cells.[51] Kim et al., demonstrated the use of near-infrared fluorescent QDs to map sentinel lymph nodes in mice and pigs during surgical procedures.[52]

Zhao et al., have attempted to identify the properties of peripheral nerve fibers by an in situ incorporation of gold nanoparticles into a biocompatible polymer film, but its utilization in clinical applications is largely restricted.[2] Optical properties of QDs are usually unaffected by conjugation to biomolecules.[53] Therefore, QDs have been covalently linked to biomolecules including peptides, antibodies, nucleic acids, or small-molecule ligands, all of which can be used as fluorescent probes.[54],[55],[56],[57],[58],[59],[60],[61] Nisman et al., employed QDs in conjunction with immunogold to co-localize proteins at the ultrastructural level.[50] Antibody-conjugated QDs allow real-time imaging and tracking of single receptor molecules on the surface of living cells with improved sensitivity and resolution,[62] thereby raising the interest of neuroscientists. Progress made in neuroscience regarding the utilization of QDs includes its applications in targeting glycine receptors,[63] serotonin transporters,[64] and synaptophysin.[65] Although no direct study regarding the usage of QDs in labeling peripheral motor or sensory nerve fascicles has been reported, QDs have been recently demonstrated to work in monitoring neural stem cells both in vitro[66] and in vivo, after being transplanted in areas that have developed an acute cerebral infarction, with satisfactory efficacy and safety.[67] In studying intracellular molecules, QDs have been used in labelling various neuronal receptors and transporters.[68] An intriguing study has reported the successful QDs-labeling of nerve growth factor receptors on rat dorsal root ganglion neurons.[69] These studies collectively suggest that QD-labeling is an ideal method for identification of motor and sensory nerve fascicles, especially during surgery.

 » Future Prospects Top

For identification of motor and sensory nerve fascicles of the peripheral nervous system, the currently available procedures, including, physical, enzyme-histological, and immunohistological methods, have their inherent disadvantages that cannot be easily overcome. This fact largely impedes the assessment of successful postoperative recovery of nerve repair surgery. Current knowledge points towards the role of three possible novel methods in fulfilling this task. These include diffusion tensor imaging, proteomics, and QD-based immunohistochemical staining. Diffusion tensor imaging can reflect more morphological details of peripheral nerves; the proteomic assay could help in investigating the dynamic protein expressional profile in a time dependant serial assessment; and, QD-immunostaining has a higher sensitivity, specificity, and rapidity. Each of these three methods have their own advantage and have the potential to be used in future clinical practice. However, as none of these methods has been tested directly in a clinical setting for the identification of motor and sensory nerve fascicles, there is a long process before they may used on patients. More studies on both animals and humans are required to find the appropriate biomarker and to elaborate the procedures. The advancement in each of these techniques will dramatically increase the successful rate of nerve repair and significantly improve postoperative functional recovery.


The procedure followed the principles outlined in the declaration of Helsinki.

Financial support and sponsorship

The Technology Progress Project of Heilongjiang Province, China (20120630-28).

Conflicts of interest

There are no conflicts of interest.

 » References Top

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  [Table 1]


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