The optimal distance between two electrode tips during recording of compound nerve action potentials in the rat median nerve

Yongping Li, Jie Lao Xin Zhao Dong Tian Yi Zhu Xiaochun Wei

1 Department of Hand Surgery of HuaShan Hospital, Fudan University; Key Laboratory of Hand Reconstruction, Ministry of Healthy; Shanghai Key Laboratory of Peripheral Nerve and Microsurgery, Shanghai, China

2 Department of Orthopedics, the Second Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China

The optimal distance between two electrode tips during recording of compound nerve action potentials in the rat median nerve

Yongping Li1,2, Jie Lao1, Xin Zhao1, Dong Tian1, Yi Zhu1, Xiaochun Wei2

1 Department of Hand Surgery of HuaShan Hospital, Fudan University; Key Laboratory of Hand Reconstruction, Ministry of Healthy; Shanghai Key Laboratory of Peripheral Nerve and Microsurgery, Shanghai, China

2 Department of Orthopedics, the Second Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, China

The distance between the two electrode tips can greatly in fl uence the parameters used for recording compound nerve action potentials. To investigate the optimal parameters for these recordings in the rat median nerve, we dissociated the nerve using different methods and compound nerve action potentials were orthodromically or antidromically recorded with different electrode spacings. Compound nerve action potentials could be consistently recorded using a method in which the middle part of the median nerve was intact, with both ends dissociated from the surrounding fascia and a ground wire inserted into the muscle close to the intact part. When the distance between two stimulating electrode tips was increased, the threshold and supramaximal stimulating intensity of compound nerve action potentials were gradually decreased, but the amplitude was not changed signi fi cantly. When the distance between two recording electrode tips was increased, the amplitude was gradually increased, but the threshold and supramaximal stimulating intensity exhibited no signi fi cant change. Different distances between recording and stimulating sites did not produce signi fi cant effects on the aforementioned parameters. A distance of 5 mm between recording and stimulating electrodes and a distance of 10 mm between recording and stimulating sites were found to be optimal for compound nerve action potential recording in the rat median nerve. In addition, the orthodromic compound action potential, with a biphasic waveform that was more stable and displayed less interference (however also required a higher threshold and higher supramaximal stimulus), was found to be superior to the antidromic compound action potential.

nerve regeneration; peripheral nerve injury; compound nerve action potential; median nerve; electrodes; amplitude; supramaximal stimulus intensity; recording electrode; the Project 211 in China; neural regeneration

Funding: This study was supported by grants from Hand Function Research Center in Fudan University, China and the Project 211 in China, No. 211XKZ.

Li YP, Lao J, Zhao X, Tian D, Zhu Y, Wei XC. The optimal distance between two electrode tips during recording of compound nerve action potentials in the rat median nerve. Neural Regen Res. 2014;9(2):171-178.

Introduction

The compound nerve action potential is evoked from many types of nerve fibers when the nerve trunk is stimulated. The waveform of a compound nerve action potential may include the compound Aαβ wave (such as the motor efferent fi ber-Aα; diameter 12–22 μm), touch-pressure sensation afferent fi ber-Aβ wave (diameter 5–12 μm), Aδ wave (such as the pain-warm sensation afferent fi ber; diameter 1–5 μm), or C wave (such as postganglionic sympathetic fi ber; diameter 0.1–1.3 μm)[1-2]. The Aαβ wave of the compound nerve action potential has been studied in the sciatic nerve[3-6], spinal nerve[7-9], tibial nerve[10-12], and peroneal nerve[13-15], as well as in the spinal cord[16-18]and the white matter of the brain[19-21]. The characteristics of Aαβ, Aδ, and C waveforms have been reviewed[22]. The compound nerve action potential, when compared with the traditional electromyogram[23-25], such as compound muscle action potential, possesses the advantages of lower volume conduction, and the ability to be recorded before the regenerated axon extends to the target muscle. The compound nerve action potential is not affected in diseases involving synapses or muscles, and can be measured directly in vivo.

Figure 1 The approaches to compound nerve action potential recording.

The compound nerve action potential has been recorded in many different species, including cats[26-27], rats[5], guinea pig[28-29], monkeys[30]and humans[23]. A similar compound nerve action potential waveform is recorded in vitro[31]or in vivo[32]. However, compound nerve action potential amplitudes can present with large disparities, even when they are recorded in the same nerve of the same species[10,33-34], which might be ascribed to different recording approaches, distances between bipolar electrodes or stimulus strengths. In recent years, there has been a growing focus on upper limb nerve models in studies of peripheral nerves. These possess many advantages, such as fewer contractions and automutilations[35-36], less mobility impairment resulting in the dragging of the affected extremity[37], and less animal distress and care burden. There have been reports incorporating the functional examination of the upper limb nerves[38-40]. To the best of our knowledge, there has been no optimal approach developed to record compound nerve action potentials in the rat median nerve in vivo. The compound nerve action potential might fail to be recorded in vivo, or its waveform can be signi fi cantly affected, due to different distances between the electrodes and different positions of electrodes. Some studies have confirmed that when the distance between the electrodes is 5 mm or more, the amplitude of compound action potentials in frog sciatic nerve in vitro is small[41]. Others have reported that the optimal distance between recording electrodes is 3–5 mm for recording compound nerve action potentials in the brachial plexus[42]. But so far, to the best of our knowledge, there has been no study reporting the results when the distance between the electrodes is less than 5 mm. In this study, we used a practical approach and explored the optimal distance between electrodes during recording of compound nerve action potentials in the rat median nerve.

Results

Approaches to compound nerve action potential recordingBoth ends of the median nerve, dissociated from the surrounding fascia, had electrodes (about 6–7 mm wide) placed, leaving the middle part of about 4–5 mm intact. The two electrodes were placed under the ends of the nerve trunk, distal and proximal to the middle. The ground wire was inserted into the muscle close to the intact part (Method A). In Method B, the median nerve was completely dissociated, and it was otherwise treated as in Method A. In Method C, the ground wire was placed beneath the middle part of the completely dissociated median nerve trunk. The bipolar electrodes were not allowed to touch the surrounding muscles and fascia tissues, with plastic fi lms used for insulation when necessary (Figure 1).

No compound nerve action potential was elicited by Method B or C. However, compound nerve action potentials could be consistently recorded using Method A with the grounding needle in the neighborhood tissues between the recording and stimulation sites (Figure 2).

Effects of different electrode spacings on compound nerve action potential

When the distances between the stimulating electrodes in the fi rst case were changed from 1.0 to 5.0 mm, the threshold intensity and supramaximal stimulating intensity of the compound nerve action potential were gradually decreased (P ＜ 0.01) and a lower threshold and supramaximal stimulus intensity were needed. Other parameters, such as firstpeak amplitude (FPA) and peak-peak amplitude (PPA),latency (LAT) and action potential duration (APD) of the compound nerve action potential were not found to be signi fi cantly different between different electrode spacings (P ＞0.05; Table 1).

Figure 2 Photograph showing arrangement of recording (Rec) and stimulating (Sti) electrodes and the grounding needle (Gnd).

In the second case, the FPA and PPA of compound nerve action potentials were gradually increased when the distance between the recording electrodes changed from 1.0 to 5.0 mm, and higher amplitudes were obtained when a wider distance was used (P ＜ 0.01). Other parameters, such as threshold intensity (THI), SSI, LAT and APD did not show any signi fi cant changes (P ＞ 0.05; Table 2, Figure 3).

In the third case, different distances between stimulating electrode and recording electrode (8, 10 or 12 mm) produced no statistically signi fi cant effect on compound nerve action potential (P ＞ 0.05; Table 3). In the fourth case, in which the wider spacing of the recording electrodes was the same as that of the stimulating ones, considerably greater FPA and PPA of compound nerve action potentials were observed (P ＜ 0.01) and lower threshold and supramaximal stimulus intensity were needed (P ＜ 0.01). However, LAT and APD of compound nerve action potentials showed no signi fi cant differences (Figure 4; P ＞ 0.05).

Figure 3 Compound nerve action potential waveform changes with varied distance between two recording needles.

Comparison of compound nerve action potentials recorded orthodromically or antidromically

The waveform of compound nerve action potentials recorded orthodromically was biphasic, and characterized by more stability and less interference, even though it required a higher threshold of 0.8–3.3 mA and a higher supramaximal stimulus of 1.8–7.8 mA (Figure 5). Antidromically, the waveform was triphasic, and characterized by inconsistency and inaccuracy, despite the lower threshold of 0.1–0.3 mA and lower supramaximal stimulus of 0.9–2.8 mA (Figure 6).

Discussion

Recording of the compound muscle action potential, a classic electrophysiological method, has diagnostic and prognostic value for assessing peripheral nerve injury[43]. But it cannot be recorded until the regenerated nerve extends to the target muscle, and the compound muscle action potential is in fl uenced by volume conduction and synaptic function. However, compound nerve action potential recording is a useful tool in the surgical management of many kinds of peripheral nerve diseases, including nerve injuries[44], neuropathy[45], and neuroma[46-47]. The presence of a compoundnerve action potential is associated with a 90% recovery to a useful motor state. Therefore, compound nerve action potential recording can provide useful information regarding the regenerative potential of a damaged nerve long before that potential is clinically evident[42].

Table 1 Effect of different distances between stimulating electrode needles on compound nerve action potential

Table 2 Effects of different distances between recording electrode needles on compound nerve action potential

Table 3 Effects of different distances between stimulating electrodes and recording electrodes on compound nerve action potential

Compound nerve action potential is the total electrical potential that develops and travels within a nerve. Once a stimulus exceeds the fi ber thresholds of a nerve, a maximal potential will be generated that will represent the electrical summation of different types of nerve fi ber potentials[4]. But differences in the recorded compound nerve action potential amplitude can be signi fi cant, even in the same nerve, e.g., the sciatic nerve[48]. Therefore, designing and developing a standard and optimal compound nerve action potential recording approach would be valuable for experimental research and clinical diagnosis.

In the current study, compound nerve action potentials failed to be elicited when the rat median nerve was completely dissociated from the surrounding fascia, regardless of the ground wire position. It was previously reported that compound nerve action potentials were recorded in the rat sciatic nerve when the tibial nerve was stimulated[34], which suggested that compound nerve action potentials could be elicited if both ends of the dissociated median nerve had electrodes placed, leaving the middle part of about 4–5 mm intact. In so doing, compound nerve action potentials were found to be elicited every time, with amplitudes close to those recorded in sciatic nerve in vitro[31]. Therefore, we believe that this approach could be of signi fi cant value, because a compound nerve action potential was elicited at the dis-tance of 8 mm between the stimulating and recording sites. Clinically, compound nerve action potentials are only elicited at a distance of over 4 cm between the corresponding sites in the human peripheral nerve. This difference could be ascribed to the smaller diameters of the rat median nerve and electrode needles. Our results showed that compound nerve action potentials recorded orthodromically required both a higher stimulating threshold and supramaximal intensity, but produced a consistent biphasic wave. Antidromically, the waveform of compound nerve action potentials consisted ofa triphasic wave, which was unstable and signi fi cantly deviated from the baseline. The biphasic wave was found to be similar to compound nerve action potentials reported previously[49]. The compound nerve action potential could be stably recorded only if the electrodes were placed appropriately, with the middle part of the median nerve (about 4–5 mm) intact.

Figure 4 Changes in compound nerve action potential (CNAP) parameters when different stimulating spacings (the same as the recording spacings) were used for recording CNAP.

Figure 5 Changes in compound nerve action potential waveform recorded orthodromically in the rat median nerve.

Figure 6 Changes in compound nerve action potential waveform recorded antidromically in the rat median nerve.

Our results further showed that compound nerve action potential amplitude increased, while the threshold and supramaximal stimulus intensity decreased gradually when the distances between the recording or stimulating electrodes were increased from 1.0 to 5.0 mm. In male bullfrog isolated sciatic nerve, Dalkilic et al.[50]found that when the recording electrode spacing changed (from 10 mm up to 55 mm the compound nerve action potential amplitude decreased gradually, duration and latency increased gradually, but the area under the waveform had no signi fi cant change. The amplitude in the aforementioned study was 5–8 mV, with action potential duration 2.5–3.5 ms and latency 0.7–2 ms. Other studies showed that as the distance between the electrodes increases (from 0.5 to 1.0, 1.5, 2.0 or 2.5 cm), the volatility becomes gradually smaller, with the waveform relatively close to the standard two-way wave between the recording electrode, and conversely, that the volatility increased as the distance between the electrodes decreased, with more complex waveforms, of multiphase wave or gravity waves and broadening stimulus artifact increases[22]. Tiel et al.[42]argued that the separation between the bipolar tips of the electrodes on the recording end of 3 to 5 mm worked well in general, and that if the distance was too short, the potential difference detected would be reduced, because both electrodes were placed in the active region of the nerve. In our study, there was a gradual increase in compound nerve action potential amplitude when the distance between the recording electrodes was scaled up from 1.0 to 5.0 mm, suggesting that the distance of 5 mm between the recording or stimulating electrodes is optimal for compound nerve action potential recording in the rat median nerve. Furthermore, compound nerve action potential recording showed no statistically signi fi cant differences when the distances between the recording and stimulating sites was changed from 8 to 12 mm. In line with previous studies[50-51], the range of compound nerve action potential amplitudes in the median nerve was from 5 to 13 mV. In the 20 right median nerve, the length of the median nerve trunk at the upper arm was about 18–22 mm, and the maximal distance between the recording electrodes or between the stimulating electrodes was about 5.0 mm. A limitation of our experiments was that no longer nerve was available, hence we were unable to test distances greater than 5 mm. Therefore, the distance of 5 mm between the recording and stimulating electrodes is optimal for compound nerve action potential recording in the rat median nerve.

In summary, compound nerve action potentials were recorded orthodromically by Method A in the median nerve, with the same distance (5.0 mm) between the two stimulating needles as that between the two recording needles, and a distance of 10 mm between recording and stimulating sites. Other parameters were 2.5 ms scan speed, 5 mV wave amplitude per division, 0.1 ms duration square wave for stimulation, 1Hz stimulating frequency, and 10 to 1,000 Hz fi ltration.

The method and optimal parameters revealed in the current study could be used in related research fi elds (such as brachial plexus injury, peripheral nerve damage, optic nerve damage and auditory nerve damage). In particular, these results provide a valuable reference for the clinical diagnosis and assessment of short injured nerves, using the compound nerve action potential recording technique together with compound muscle action potential.

Materials and methods

Design

Matched pairs design.

Time and setting

The experiments were performed at Experimental Animal Center of Fudan University in China in June 2011.

Materials

Twenty Sprague-Dawley male rats (10 weeks old, 280–330 g), were purchased from Experimental Animal Center of Fudan University in China (license No. SYXK (Hu) 2009-0082). Ethically, the experiments were approved by Fudan University Animal Care and Use Committee in China. All efforts were made to minimize the number of animals used and their distress.

Methods

Median nerve preparation

Each rat was anesthetized by intraperitoneal injection of 1% sodium pentobarbital solution (40 mg/kg), and placed in the dorsal position.

A longitudinal incision was performed at the anteromedial site extending from the ectopectoralis to the elbow region, with the right median nerve exposed over the length of the upper arm. The nerve was continuously moistened with normal saline to avoid desiccation.

Electrophysiological measurement

Compound nerve action potentials were recorded with 0.2 mm diameter bipolar stainless steel electrodes (Medtronic Keypoint Systems, Dantec corporation, Denmark). Recording parameters were scan speed 2.5 ms, wave amplitude 5 mV per division, stimulus square wave duration 0.1 ms, stimulating frequency 1 Hz, and fi ltration from 10 to 1,000 Hz. Distances were measured with a vernier caliper, and skin temperature was maintained at approximately 36°C (Vital Sense Monitor, American Health & Medical Supply International Corp) in a room maintained at a constant temperature of 26°C. Three different methods (Method A, B and C; Figure 1) were used to record compound nerve action potentials. The bipolar electrodes were not allowed to touch the surrounding muscles and fascia tissues, with plastic fi lms used for insulation when necessary.

To explore optimal electrode distances, compound nerve action potentials were recorded with various distances between electrodes. In the first case, compound nerve actionpotentials were elicited with distances of 1.0, 2.0, 3.0, 4.0 or 5.0 mm between the two needles of the stimulating electrode, while the distance between the two needles of the recording electrode was maintained at 5.0 mm. Conversely, in the second case, fi ve different distances between the two needles of the recording electrode were tested, while the distance between the two needles of the stimulating electrode was kept at 5.0 mm. In the third case, distances of 8, 10 and 12 mm between the recording and stimulating sites were tested, while the distances between the recording and stimulating electrode needles were kept constant. In the fourth case, wider spacing of the recording electrodes (the same as that of the stimulating electrodes) was applied and the effects on compound nerve action potential were analyzed. Finally, the parameters of compound nerve action potentials recorded orthodromically (recorded in the proximal segment with the distal segment stimulated), were compared with those recorded antidromically, in terms of waveform, baseline and amplitude.

Statistical analysis

The data were analyzed using the SPSS 16.0 software package (IBM Corporation, New York, NY, USA) and are presented as mean ± SEM. One-way analysis of variance followed by Student-Newman-Keuls test was applied for comparisons of amplitude, stimulating intensity, latency and action potential duration between different groups. A value of P ＜ 0.05 was considered statistically signi fi cant.

Author contributions:Li YP was responsible for animal preparation, data acquisition and integration, analyzed experimental data, drafted the paper and provided data support. Lao J had full access to study concept and design, validated the paper and was in charge of funds. Zhao X participated in statistical analysis. Tian D was responsible for electrophysiological testing. Zhu Y was responsible for electrophysiological method design and electrophysiological testing. Wei XC participated in study design and statistical analysis. All authors approved the final version of this paper.

Con fl icts of interest:None declared.

Peer review:This study found the optimal distance, including the distance between two recording electrode tips, the distance between two stimulating electrode tips and the distances between recording and stimulating sites, when compound nerve action potential was recorded in rat median nerve. These findings provide some help in the evaluation and treatment of short injured nerve using compound nerve action potential in the clinic.

[1] Manzano GM, Giuliano LM, Nobrega JA. A brief historical note on the classification of nerve fibers. Arq Neuropsiquiatr. 2008;66(1):117-119.

[2] Ordelman SC, Kornet L, Cornelussen R, et al. An indirect component in the evoked compound action potential of the vagal nerve. J Neural Eng. 2010;7(6):066001.

[3] Brown AM, Evans RD, Black J, et al. Schwann cell glycogen selectively supports myelinated axon function. Ann Neurol. 2012;72(3):406-418.

[4] Joseph L, Butera RJ. High-frequency stimulation selectively blocks different types of fibers in frog sciatic nerve. IEEE Trans Neural Syst Rehabil Eng. 2011;19(5):550-557.

[5] Yilmaz-Rastoder E, Gold MS, Hough KA, et al. Effect of adjuvant drugs on the action of local anesthetics in isolated rat sciatic nerves. Reg Anesth Pain Med. 2012;37(4):403-409.

[6] Tomohiro D, Mizuta K, Fujita T, et al. Inhibition by capsaicin and its related vanilloids of compound action potentials in frogsciatic nerves. Life Sci. 2013;92(6-7):368-378.

[7] Zhang L, Zhang CG, Dong Z, et al. Spinal nerve origins of the muscular branches of the radial nerve: an electrophysiological study. Neurosurgery. 2012;70(6):1438-1441.

[8] Singh A, Kallakuri S, Chen C, et al. Structural and functional changes in nerve roots due to tension at various strains and strain rates: an in-vivo study. J Neurotrauma. 2009;26(4):627-640.

[9] Matsuka Y, Spigelman I. Hyperosmolar solutions selectively block action potentials in rat myelinated sensory fi bers: implications for diabetic neuropathy. J Neurophysiol. 2004;91(1):48-56.

[10] Ichihara S, Inada Y, Nakada A, et al. Development of new nerve guide tube for repair of long nerve defects. Tissue Eng Part C Methods. 2009;15(3):387-402.

[11] Barkhaus PE, Kincaid JC, Nandedkar SD. Tibial motor nerve conduction studies: an investigation into the mechanism for amplitude drop of the proximal evoked response. Muscle Nerve. 2011;44(5):776-782.

[12] Kovacic U, Tomsic M, Sketelj J, et al. Collateral sprouting of sensory axons after end-to-side nerve coaptation--a longitudinal study in the rat. Exp Neurol. 2007;203(2):358-369.

[13] Nikolaeva MA, Richard S, Mouihate A, et al. Effects of the noradrenergic system in rat white matter exposed to oxygen-glucose deprivation in vitro. J Neurosci. 2009;29(6):1796-1804.

[14] Ochs S, Pourmand R, Si K, et al. Stretch of mammalian nerve in vitro: effect on compound action potentials. J Peripher Nerv Syst. 2000;5(4):227-235.

[15] Geronikaki A, Vicini P, Theophilidis G, et al. Study of local anesthetic activity of some derivatives of 3-amino-benzo-[d]-isothiazole. SAR QSAR Environ Res. 2003;14(5-6):485-495.

[16] Eftekharpour E, Karimi-Abdolrezaee S, Wang J, et al. Myelination of congenitally dysmyelinated spinal cord axons by adult neural precursor cells results in formation of nodes of Ranvier and improved axonal conduction. J Neurosci. 2007;27(13):3416-3428.

[17] Velumian AA, Wan Y, Samoilova M, et al. Contribution of fast and slow conducting myelinated axons to single-peak compound action potentialsin rat spinal cord white matter preparations. J Neurophysiol. 2011;105(2):929-941.

[18] Velumian AA, Wan Y, Samoilova M, et al. Modular double sucrose gap apparatus for improved recording of compound action potentials from rat and mouse spinal cord white matter preparations. J Neurosci Methods. 2010;187(1):33-40.

[19] Park E, Eisen R, Kinio A, et al. Electrophysiological white matter dysfunction and association with neurobehavioral de fi cits following low-level primary blast trauma. Neurobiol Dis. 2013;52:150-159.

[20] Hamner MA, M?ller T, Ransom BR. Anaerobic function of CNS white matter declines with age. J Cereb Blood Flow Metab. 2011;31(4):996-1002.

[21] Baker AJ, Phan N, Moulton RJ, et al. Attenuation of the electrophysiological function of the corpus callosum after fl uid percussion injury in the rat. J Neurotrauma. 2002;19(5):587-599.

[22] Julius D, Basbaum AI. Molecular mechanisms of nociception. Nature. 2001;413(6852): 203-210.

[23] Butterworth J, Ririe DG, Thompson RB, et al. Differential onset of median nerve block: randomized, double-blind comparison of mepivacaine and bupivacaine in healthy volunteers. Br J Anaesth. 1998;81(4):515-521.

[24] Di Sapio A, Bertolotto A, Melillo F, et al. A new neurophysiological approach to assess central motor conduction damage to proximal and distal muscles of lower limbs. Clin Neurophysiol. doi: 10.1016/j.clinph.2013.06.018.

[25] Plate JF, Pace LA, Seyler TM, et al. Age-related changes affect rat rotator cuff muscle function. J Shoulder Elbow Surg. doi: 10.1016/ j.jse.2013.04.017.

[26] Davis LA, Gordon T, Hoffer JA, et al. Compound action potentials recorded from mammalian peripheral nerves following ligation or resuturing. J Physiol. 1978;285:543-559.

[27] Agnew WF, McCreery DB, Yuen TG, et al. Histologic and physiologic evaluation of electrically stimulated peripheral nerve: considerations for the selection of parameters. Ann Biomed Eng. 1989;17(1):39-60.

[28] Li J, Shi R. Stretch-induced nerve conduction de fi cits in guinea pig ex vivo nerve. J Biomech. 2007;40(3):569-578.

[29] Li J, Shi R. A device for the electrophysiological recording of peripheral nerves in response to stretch. J Neurosci Methods. 2006;154(1-2):102-108.

[30] Archibald SJ, Shefner J, Krarup C, et al. Monkey median nerve repaired by nerve graft or collagen nerve guide tube. J Neurosci. 1995;15(5 Pt 2):4109-4123.

[31] Moschou M, Kosmidis EK, Kaloyianni M, et al. In vitro assessment of the neurotoxic and neuroprotective effects of N-acetyl-L-cysteine (NAC) on the rat sciatic nerve fibers. Toxicol In Vitro. 2008;22(1):267-274.

[32] Hausner T, Pajer K, Halat G, et al. Improved rate of peripheral nerve regeneration induced by extracorporeal shock wave treatment in the rat. Exp Neurol. 2012;236(2):363-370.

[33] Archibald SJ, Shefner J, Krarup C, et al. Monkey median nerve repaired by nerve graft or collagen nerve guide tube. J Neurosci. 1995;15(5 Pt 2):4109-4123.

[34] Murphy B, Krieger C, Hoffer JA. Chronically implanted epineural electrodes for repeated assessment of nerve conduction velocity and compound action potential amplitude in 13 rodents. J Neurosci Methods. 2004;132(1):25-33.

[35] Lee JM, Tos P, Raimondo S, et al. Lack of topographic speci fi city in nerve fi ber regeneration of rat forelimb mixed nerves. Neuroscience. 2007;144(3):985-990.

[36] Tos P, Calcagni M, Gigo-Benato D, et al. Use of muscle-vein-combined Y-chambers for repair of multiple nerve lesions: experimental results. Microsurgery. 2004;24(6):459-464.

[37] Sinis N, Schaller HE, Becker ST, et al. Cross-chest median nerve transfer: a new model for the evaluation of nerve regeneration across a 40 mm gap in the rat. J Neurosci Methods. 2006;156(1-2):166-172.

[38] Wang H, Spinner RJ, Sorenson EJ, et al. Measurement of forelimb function by digital video motion analysis in rat nerve transection models. J Peripher Nerv Syst. 2008;13(1):92-102.

[39] Galtrey CM, Fawcett JW. Characterization of tests of functional recovery after median and ulnar nerve injury and repair in the rat forelimb. J Peripher Nerv Syst. 2007;12(1):11-27.

[40] Metz GA, Whishaw IQ. Cortical and subcortical lesions impair skilled walking in the ladder rung walking test: a new task to evaluate fore- and hindlimb stepping, placing, and coordination. J Neurosci Methods. 2002;115:169-179.

[41] Jiang XW, Zhou J, Sun H, et al. Effects of the arrangement of electrodes and earthing line and the width of electrodes on the action potential of sciatic nerve in toads. Xuzhou Yixueyuan Xuebao. 2006;26(5)423-425.

[42] Tiel RL, Happel LT Jr, Kline DG. Nerve action potential recording method and equipment. Neurosurgery. 1996;39(1):103-108.

[43] Rutz S, Dietz V, Curt A. Diagnostic and prognostic value of compound motor action potential of lower limbs in acute paraplegic patients. Spinal Cord. 2000;38(4):203-210.

[44] Kim DH, Murovic JA, Kim YY, et al. Surgical treatment and outcomes in 45 cases of posterior interosseous nerve entrapments and injuries. J Neurosurg. 2006;104(5):766-777.

[45] Kim DH, Murovic JA, Tiel RL, et al. Operative outcomes of 546 Louisiana State University Health Sciences Center peripheral nerve tumors. Neurosurg Clin N Am. 2004;15(2):177-192.

[46] Kim DH, Murovic JA, Kim YY, et al. Surgical treatment and outcomes in 15 patients with anterior interosseous nerve entrapments and injuries. J Neurosurg. 2006;104(5):757-765.

[47] Oberle JW, Antoniadis G, Rath SA, et al. Value of nerve action potentials in the surgical management of traumatic nerve lesions. Neurosurgery. 1997;41(6):1337-1342.

[48] Mizuta K, Fujita T, Nakatsuka T, et al. Inhibitory effects of opioids on compound action potentials in frog sciatic nerves and their chemical structures. Life Sci. 2008;83(5-6):198-207.

[49] Takarada Y, Nozaki D, Taira M. Force overestimation during tourniquet-induced transient occlusion of the brachial artery and possible underlying neural mechanisms. Neurosci Res. 2006;54(1):38-42.

[50] Dalkilic N, Kiziltan E, Pehlivan F, et al. Does collagenase affect the electrophysiological parameters of nerve trunk? Yakugaku Zasshi. 2003;123 (12):1031-1037.

[51] Wells J, Kao C, Konrad P, et al. Biophysical mechanisms of transient optical stimulation of peripheral nerve. Biophys J. 2007;93(7):2567-2580.

Copyedited by Black M, Yajima M, Zhang Y, Huang G, Li CH, Song LP, Liu WJ, Zhao M

10.4103/1673-5374.125346

Jie Lao, Ph.D., Department of Hand Surgery, HuaShan Hospital, No. 12 Wu-LuMuQi Zhong Road, Shanghai 200040, China, laojie666@163.com.

http://www.nrronline.org/

Accepted: 2013-09-01