Authors: Young-Eun Moon, MD, PhD Sang-Hyun Kim, MD, PhD

Pain

Affiliations: From the Department of Anesthesiology and Pain Medicine, Catholic University, Seoul St. Mary’s Hospital, Seoul (Y-EM); and Department of Physical Medicine and Rehabilitation, College of Medicine, Soonchunhyang University, Bucheon, Republic of Korea (S-HK).

Correspondence: All correspondence and requests for reprints should be addressed to: Sang-Hyun Kim, MD, PhD, Department of Physical Medicine and Rehabilitation, College of Medicine, Soonchunhyang University, 1174 Jung-dong, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-767, Republic of Korea.

Disclosures: This research was supported by the Soonchunhyang University Research Fund and the Catholic University Research Fund. Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article.

0894-9115/14/9310-0869 American Journal of Physical Medicine & Rehabilitation Copyright * 2014 by Lippincott Williams & Wilkins DOI: 10.1097/PHM.0000000000000106

ORIGINAL RESEARCH ARTICLE

Effects of Ethyl Chloride Spray on Pain and Parameters of Needle Electromyography in the Upper Extremity ABSTRACT Moon Y-E, Kim S-H: Effects of ethyl chloride spray on pain and parameters of needle electromyography in the upper extremity. Am J Phys Med Rehabil 2014;93:869Y875.

Objective: The aim of this study was to compare the effects of ethyl chloride and placebo sprays for reducing pain induced by needle electromyography and changes in parameters of the motor unit action potential during needle electromyography of the upper extremity. Design: Sixty patients were randomized into the ethyl chloride or placebo spray groups. In both groups, spray was applied just before needle electromyography of the flexor carpi radialis, and a visual analog scale to evaluate the pain of needle electromyography and a five-point Likert scale for patient satisfaction and preference for reexamination were compared between the two groups. Then, changes in the amplitude, phases, turns, and duration of the motor unit action potential during needle electromyography of the biceps brachii were compared before and after spraying in each group.

Results: The visual analog scale was significantly lower, and patient satisfaction and preference for reexamination were significantly higher in the ethyl chloride spray group. Among the parameters of the motor unit action potential, there were no significant changes except for an increased duration after spraying with ethyl chloride.

Conclusions: Ethyl chloride spray can effectively reduce pain, but it must be used with caution because it may affect parameters of the motor unit action potential during needle electromyography. Key Words:

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Ethyl Chloride, Pain, Electromyography, Action Potentials

Ethyl Chloride Spray Reduces Pain Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

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eedle electromyography is an important tool for detecting the abnormalities in the neuromuscular system, but it induces significant pain. Several methods have been attempted to reduce the pain, but they require time to take effect and/or may cause side effects.1Y3 Ethyl chloride spray has been used for decades to safely reduce the symptoms of myofascial pain syndromes,4 and it has also been used in several minor invasive procedures such as intravenous cannulation and vaccination.5,6 It has been recently found that ethyl chloride spray is more effective than topical anesthetic cream for reducing pain during needle electromyography of the gastrocnemius.7 However, any effects of cooling on the parameters of the motor unit action potential (MUAP) were not investigated, which might be affected by focal cooling induced by evaporation.8 Moreover, it has not been examined whether these analgesic effects might also be effective for a needle electromyography of the muscles of the upper extremity, for which a different caliber of needle electrode is ordinarily used. Thus, the efficacy of ethyl chloride spray on pain associated with needle electromyography of the upper extremity by comparison with a placebo (water) spray was assessed, and variation in the parameters of MUAP after applying the ethyl chloride and placebo sprays was measured.

METHODS All participants were informed of the procedure and objectives of this study. Only patients who gave informed consent were selected. Ethical approval was obtained from the institutional Human Research Ethics Committee.

Participants The study was conducted in patients who were at least 19 yrs old who underwent a normal schedule of needle electromyography in the upper extremity at the university hospital’s electromyographic clinic. Exclusion criteria were as follows: those who were unable to understand a visual analog scale (VAS) or a Likert scale, those with a history of cold intolerance or cold allergy, those who took pain medications or had used topical anesthetics within the previous 24 hrs, those who exhibited an abnormal upper extremity sensation on neurologic examination, and those who showed preexisting pain in the biceps brachii or flexor carpi radialis (FCR) muscle before the study.

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Using computer-generated codes placed in sequentially numbered, opaque, sealed packs, the enrolled patients were randomly assigned to one of the two groups: the ethyl chloride spray group or the placebo spray group.

Ethyl Chloride and Placebo Sprays The ethyl chloride spray (Walter Ritter GmbH and Co., Hamburg, Germany) consisted of liquefied and compressed ethyl chloride, supplied in a handheld pressurized spray can. The placebo spray was Evian Eau Minerale Naturelle, a pure water spray with hydrocarbon propellant. This product is used to provide a mist on the skin during hot weather. It is also packed in a handheld pressurized spray can of approximately the same size as the ethyl chloride spray. The ethyl chloride and placebo spray containers were masked in white paper.

Outcome Measures First, pain induced by the needle electromyography of the FCR was assessed using a 100-mm VAS as well as patients’ satisfaction about the spray using a five-point Likert scale. The 100-mm VAS consisted of a 100-mm horizontal line labeled ‘‘no pain’’ at the left and ‘‘worst pain imaginable’’ at the right. The five-point Likert scale (1, strongly agree; 2, agree; 3, undecided; 4, disagree; and 5, strongly disagree) was used to answer two questions: ‘‘Are you satisfied with the spray used before performing the electromyography?’’ and ‘‘Would you use the spray applied today again if the electromyography is repeated in the future?’’ Second, to evaluate the effects of spraying on the parameters of MUAP, changes in the amplitude, phases, turns, and duration of the MUAPs were analyzed, evaluated by needle electromyography of the biceps brachii before and after spraying. Each patient was seated in a straight-backed chair with the elbow flexed at 90 degrees and his/her forearm in supination, resting on a custom-built arm tray, which was designed to stabilize flexion and extension contractions of the elbow. Maximal isometric flexion force of the biceps brachii was measured using a handheld dynamometer (Lafayette Instrument, Indiana) secured to a strap around the wrist. To acquire the same contractile force before and after spraying, patients had been instructed to maintain the same force (5%Y30% of maximal isometric flexion force) displayed on the handheld dynamometer during each analysis (Fig. 1). MUAPs were collected by automatic analysis using Dantec keypoint electromyography equipment

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FIGURE 1 Experimental setup for the needle electromyography of the biceps brachii. A monopolar needle was inserted into the motor point of the biceps brachii and anchored to the custom-built arm tray. The arm tray had a prop and straps to stabilize the upper extremity during contraction of the biceps brachii. A handheld dynamometer was used to monitor the isometric force of the biceps brachii.

(Alpine Biomed, Skovlunde, Denmark) in each session before and after spraying. The amplifier filter was set to 20Y10 kHz, with a sweep speed of 5 ms/div and gain of 500 KV/div. In each session, 30 MUAPs were collected for data analyses.

Study Process The examination room was divided into two sections (examination and waiting sections) using a blinded partition, for prompt coming and going by the investigators. Room temperature was kept at 25-C. Before needle electromyography, the patients were informed about how to use the VAS and the Likert scale. Then, patient anxiety about needle electromyography was measured using a five-point Likert scale with the following statement: ‘‘I am anxious about undergoing a needle electromyography.’’ After that, the patient was positioned on the table in a supine posture, and the electromyography needle insertion site (FCR) was marked with an indelible pen and sterilized using an alcohol gauze. The secondary investigator (electromyographer), who was blinded to the study process, carried out these processes, then left the examination section, and went behind the partition. Then, the principal investigator (spray administrator) entered the examination section, opened the sealed envelope, and prepared to administer the assigned spray. Because of the slight difference between the two sprays (transient skin blanching and jet force), the principal investigator could not be www.ajpmr.com

blinded. Because the ethyl chloride spray had a slight fragrance and a different jet sound that could potentially disrupt the effective blinding of the secondary investigator, a simultaneous 5-sec spray was performed with both cans, with the assigned one targeted to the insertion site (FCR muscle) from a distance of 30 cm and the other one targeted to the open air. Immediately after spraying, the principal investigator left, and the secondary investigator entered the examination section to sterilize the insertion site again using an alcohol gauze and to insert a 37-mm 28-G monopolar electromyographic needle (Alpine Biomed, San Carlos, CA). Then, the needle electrode was moved at an angle to perform the routine test in four directions.8 Immediately after finishing the needle electromyography of the FCR, each patient was asked to fill out the self-administered documents for assessing pain, seal them in an envelope, and submit them to the researchers. Then, the patient changed to a sitting position for needle electromyography to evaluate the parameters of MUAPs of biceps brachii. The secondary investigator sterilized the other insertion site (biceps brachii), inserted a 37-mm 28-G monopolar electromyographic needle, and fixed the needle to the custom-built arm tray using tongs. The surface reference Ag/AgCl disk electrode was placed within 1 cm of the recording electrode (Fig. 1). The patient contracted the biceps brachii isometrically, and MUAPs were collected. Then, the principal investigator changed places with the secondary investigator and sprayed the target site as described previously. Immediately after spraying, the secondary investigator entered the examination section again and gathered another set of MUAP data. At the end of the study, the insertion site was observed for redness, itching, swelling, or damage caused by cold.

Statistical Analysis On the basis of a previous study by the authors,7 the anticipated pain for needle electromyography was 55.0 (SD, 14.0). A 20% reduction in pain was considered to be clinically relevant. With a power of 80% and an > of 0.05 (two sided), 27 patients were required in each study group. To compensate for potential dropouts, 30 patients were enrolled in each group. The VAS scores of the two groups were compared using an independent samples t test. Patient satisfaction and preferences regarding spraying were Ethyl Chloride Spray Reduces Pain

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TABLE 1 General characteristics of the patients

Age, mean (SD, range), yrs Sex (male/female) BMI, mean (SD), kg/m2 Level of anxiety about the needle electromyography, median (interquartile range)

Ethyl Chloride Spray (n = 30)

Placebo Spray (n = 30)

48.30 (11.15, 21Y67) 12/18 22.84 (2.41) 2 (1Y3)

49.77 (13.62, 20Y77) 13/17 22.73 (2.62) 2 (1Y3)

BMI, body mass index.

compared between the two groups using W2 analyses. Paired t tests were used to examine whether there was a significant change in MUAP parameters before and after spraying in each group, and the mean value of 30 MUAPs was used for analysis. P values G 0.05 were considered to indicate statistical significance. All data were analyzed using the SPSS software (version 15 for Windows).

RESULTS In total, 60 patients were enrolled: 30 in the ethyl chloride spray group and 30 in the placebo spray group. The groups did not differ in patient characteristics or anxiety about electromyography needle insertion (see Table 1). The VAS scores after needle electromyography of the FCR muscle were 35.53 (95% confidence interval, 30.53Y40.54) for the ethyl chloride spray group and 45.03 (95% confidence interval, 39.65Y50.42) for

the placebo spray group. The pain intensity was significantly lower in the ethyl chloride spray group than in the placebo spray group (P = 0.011; Fig. 2). Patient satisfaction was also significantly higher in the ethyl chloride group than in the placebo group (see Table 2). In response to the question ‘‘Are you satisfied with the spray used before performing the electromyography?’’, 73.3% of the ethyl chloride group strongly agreed or agreed. In contrast, only 26.7% of the placebo group did so. In response to the question ‘‘Would you use the spray applied today again if the electromyography is repeated in the future?’’, 73.3% of the ethyl chloride group and 23.3% of the placebo group strongly agreed or agreed. There was no significant difference in the amplitude, phases, or turns of the MUAPs of the biceps brachii before and after spraying in each group. However, the duration of MUAPs significantly increased after spraying in the ethyl chloride group.

FIGURE 2 VAS for pain during needle electromyography of the FCR. Box plots indicate the mean (upper margin of the box plots) and the upper bound of the 95% confidence interval (upper whisker). *P = 0.011, compared with each other.

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Am. J. Phys. Med. Rehabil. & Vol. 93, No. 10, October 2014

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TABLE 2 Patient’s satisfaction about spraying Are You Satisfied With the Spray Used Before Performing the Electromyography?a Five-Point Likert Scale

Would You Use the Spray Applied Today Again if the Electromyography is Repeated in the Future?a

Ethyl Chloride Spray

Placebo Spray

Ethyl Chloride Spray

Placebo Spray

9 13 3 3 2

4 4 1 10 11

14 8 2 4 2

3 4 6 8 9

Strongly agree Agree Undecided Disagree Strongly disagree

Values are number. a Significantly different between ethyl chloride spray and placebo spray (P G 0.05).

In comparison, there was no significant difference in the duration before and after spraying in the placebo group (see Table 3). There were no side effects of either spraying method.

DISCUSSION Ethyl chloride spray reduced the pain of needle electromyography of the FCR muscle more effectively and resulted in greater satisfaction and preference than the placebo spray did. Ethyl chloride spray decreases pain via evaporation-induced skin cooling, directly suppressing pain receptor sensitivity and indirectly modulating pain perception via cold sensation transmitted along A delta fibers.9,10 Previously, it was found that ethyl chloride spray suppressed pain during needle electromyography of the lower extremity more effectively than did topical anesthetic cream.7 One difference between the present study and the previous study is that, this time, there was a control group using a placebo spray with properties similar to the ethyl chloride spray. A spray allows instant application, prompt effect, and convenience. Weiss and Lavin11 reported that ethyl chloride spray markedly reduced the procedure time of cosmetic botulinum toxin injections. Waterhouse et al.12 found that patients

were satisfied with an ethyl chloride spray during intravenous injections and preferred it significantly for future use. In this study, the ethyl chloride spray group showed greater satisfaction and willingness to reuse the same method for future electromyography than did the placebo spray group. Because the treatment and placebo were both sprays, this preference may indicate a genuine painreducing effect of the ethyl chloride spray. When comparing the MUAP parameters, the amplitude, phases, and turns did not change significantly between before and after spraying in either group. However, the duration of MUAP increased significantly after using the ethyl chloride spray. As the MUAP parameters are influenced by muscle fibers only 2Y2.5 mm from the active electrode, they can be affected by subtle needle displacement.13 Therefore, the upper extremity of the patients was strapped, and the electromyography needle was fastened with a custom-made device to keep it still before and after spraying. Consequently, the increase in the duration of the MUAP seems to have been caused by the cooling effect of the ethyl chloride spray. MUAP duration is defined as the time between its start and endpoints and is influenced by the number of muscle fibers in the motor unit, the

TABLE 3 Comparison of the parameters of motor unit action potentials during the needle electromyography of the biceps brachii before and after spraying Ethyl Chloride Spray Parameters

Before Spraying

After Spraying

Placebo Spray Before Spraying

After Spraying

Amplitude, KV 680.53 (587.61Y773.46) 700.93 (626.43Y775.43) 690.00 (577.86Y802.14) 644.43 (552.38Y736.48) Duration, msec 9.45 (8.56Y10.33)a 11.36 (10.57Y12.15)a 8.77 (8.03Y9.52) 9.01 (8.20Y9.83) Phase 3.03 (2.82Y3.24) 3.04 (2.85Y3.23) 2.78 (2.64Y2.93) 2.71 (2.56Y2.86) Turns 2.68 (2.39Y2.97) 2.84 (2.58Y3.09) 2.41 (2.21Y2.61) 2.36 (2.15Y2.57) Values are mean (range of 95% confidence interval). a P G 0.05.

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temporal dispersion of the activation times of the muscle fibers, and variations in conduction velocities.14 Few studies have evaluated the effects of cooling on MUAP parameters. Buchthal et al.15 found an increase in the duration of the MUAP recorded from the biceps brachii after focal cooling with ice bags. Bertram et al.16 also reported that focal cooling of the first dorsal interosseous muscle resulted in prolonged MUAP duration but no significant change in amplitude or turns, consistent with this study’s results. They suggested that the asynchrony of individual muscle fiber action potentials, caused by accentuated dissimilarities between the fastest and slowest conducting nerve fibers and the fastest and slowest muscle fiber action potential propagations within the cooled muscle, increases the duration of the MUAP. When applying ice, superficial tissues such as the skin and subcutaneous tissue cool rapidly and profoundly, whereas deeper tissues such as the muscle exhibit a smaller, more gradual decline in temperature.17 Enwemeka et al.18 measured the temperature of skin at the surface and 1, 2, and 3 cm below the surface after 20 mins of cold pack therapy. There was a significant drop in temperature at the surface and at 1 cm, but not at deeper points. The evaporation temperature of ethyl chloride aerosol during spraying is j3-C,19 and depending on the application time and method, it can decrease the temperature of the skin from 32.5-C to below 10-C.9,20 Borken and Bierman21 reported that spraying with ethyl chloride for 15Y30 mins reduced the skin temperature to 10-C, whereas the muscle temperature fell by only 1.1-CY4.2-C. Moreover, it required several minutes for the change in muscle temperature to become evident. In this study, despite the change in the duration of the MUAP, ethyl chloride spraying did not affect other electrodiagnostic parameters of needle electromyography, possibly because of the short application time (approximately 5 secs). In addition, areas of the body with thicker skin folds may show more stable electrodiagnostic parameters after ethyl chloride spraying because there may be less temperature transfer to muscle in such areas. The thermal conductivity of adipose tissue is low (0.19 W/m/-C) compared with that of the skin (0.96 W/m/-C) or muscle (0.64 W/m/-C).22 Therefore, the thicker the adipose tissue is, the weaker is the cooling effect on muscle tissue. Patients with skin folds of 20Y30 and 30Y40 mm require two and three times the duration of cryotherapy, respectively, to produce the same cooling effect as observed in the muscle of patients with skin folds less than 20 mm.23 Thus, body

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regions with thicker skin folds, such as the deltoid (15.7 [6.7] mm in men, 20.7 [11.4] mm in women)24 and thigh (14.2 [6.3] mm in men, 23.8 [8.0] mm in women), may experience a reduced cooling effect, which might result in more stationary MUAP parameters during needle electromyography after ethyl chloride spraying, compared with areas such as the forearm (5.4 [2.6] mm in men, 8.4 [3.8] mm in women). Further studies are required to evaluate the changes in MUAP parameters after ethyl chloride spraying at sites with different skin-fold thicknesses. There are a few limitations to this study. First, the automatic analysis of the MUAP needle electromyographic parameters requires a stable baseline. When the baseline is noisy, the cursor settings become incorrect and have to be reset manually for 20%Y30% of the MUAPs.25 Although having no experience with concentric needles, a steadier baseline might be obtained if a concentric needle had been used. However, approximately 30% of MUAPs required manual correction in this study, and this proportion is in line with previous studies.25,26 Second, the intramuscle temperature was not measured directly because doing so is very painful. However, direct measurement of intramuscle temperature might be required in future studies to investigate the effect of vapocoolant spray on the MUAP parameters accurately. In conclusion, ethyl chloride spray effectively reduces the pain of needle electromyography of the FCR. However, it might also influence the MUAP electrodiagnostic parameters and should be used with caution. Future studies should examine the effects of ethyl chloride spray on the needle electromyography parameters at sites with different skin-fold thicknesses, evaluating the intramuscular temperatures directly. ACKNOWLEDGMENTS

The authors thank Sung Won Park, MD, for the assistance with the needle electromyography. REFERENCES 1. Kaplan RM, Metzger G, Jablecki C: Brief cognitive and relaxation training increases tolerance for a painful clinical electromyographic examination. Psychosom Med 1983;45:155Y62 2. El-Salem K, Shakhatreh M: Prospective double-blind crossover trial of ibuprofen in reducing EMG pain. Muscle Nerve 2008;38:1016Y20 3. Lamarche Y, Lebel M, Martin R: EMLA partially relieves the pain of EMG needling. Can J Anaesth 1992;39:805Y8

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4. Travell J: Ethyl chloride spray for painful muscle spasm. Arch Phys Med Rehabil 1952;33:291Y8

physiological determinants. Acta Physiol Scand 1954; 32:219Y29

5. Cohen Reis E, Holubkov R: Vapocoolant spray is equally effective as EMLA cream in reducing immunization pain in school-aged children. Pediatrics 1997;100:E5

16. Bertram MF, Nishida T, Minieka MM, et al: Effects of temperature on motor unit action potentials during isometric contraction. Muscle Nerve 1995; 18:1443Y6

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17. Akgun K, Korpinar MA, Kalkan MT, et al: Temperature changes in superficial and deep tissue layers with respect to time of cold gel pack application in dogs. Yonsei Med J 2004;45:711Y8

7. Moon YE, Kim SH, Choi WH: Comparison of the effects of vapocoolant spray and topical anesthetic cream on pain during needle electromyography in the medial gastrocnemius. Arch Phys Med Rehabil 2013;94:919Y24 8. Dumituru D: Needle electromyography, in Dumituru D (ed): Electrodiagnostic Medicine. Philadelphia, PA, Hanley & Belfus, 2002, pp. 211Y48 9. Kunesch E, Schmidt R, Nordin M, et al: Peripheral neural correlates of cutaneous anaesthesia induced by skin cooling in man. Acta Physiol Scand 1987; 129:247Y57 10. Yarnitsky D, Ochoa JL: Release of cold-induced burning pain by block of cold-specific afferent input. Brain 1990;113(pt 4):893Y902 11. Weiss RA, Lavin PT: Reduction of pain and anxiety prior to botulinum toxin injections with a new topical anesthetic method. Ophthal Plast Reconstr Surg 2009;25:173Y7 12. Waterhouse MR, Liu DR, Wang VJ: Cryotherapeutic topical analgesics for pediatric intravenous catheter placement: Ice versus vapocoolant spray. Pediatr Emerg Care 2013;29:8Y12 13. Nandedkar SD, Barkhaus PE, Sanders DB, et al: Analysis of amplitude and area of concentric needle EMG motor unit action potentials. Electroencephalogr Clin Neurophysiol 1988;69:561Y7 14. Calder KM, Agnew MJ, Stashuk DW, et al: Reliability of quantitative EMG analysis of the extensor carpi radialis muscle. J Neurosci Methods 2008; 168:483Y93 15. Buchthal F, Pinell P, Rosenfalck P: Action potential parameters in normal human muscle and their

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18. Enwemeka CS, Allen C, Avila P, et al: Soft tissue thermodynamics before, during, and after cold pack therapy. Med Sci Sports Exerc 2002;34:45Y50 19. Lacour M, Le Coultre C: Spray-induced frostbite in a child: A new hazard with novel aerosol propellants. Pediatr Dermatol 1991;8:207Y9 20. Im YG, Park HJ, Chae HY, et al: Comparison of changes in facial skin temperature caused by ethyl chloride spraying, ice block rubbing and cold gel packing in healthy subjects. J Oral Rehabil 2012; 39:931Y40 21. Borken N, Bierman W: Temperature changes produced by spraying with ethyl chloride. Arch Phys Med Rehabil 1955;36:288Y90 22. Sapega AA, Heppenstall RB, Sokolow DP, et al: The bioenergetics of preservation of limbs before replantation. The rationale for intermediate hypothermia. J Bone Joint Surg Am 1988;70:1500Y13 23. Otte JW, Merrick MA, Ingersoll CD, et al: Subcutaneous adipose tissue thickness alters cooling time during cryotherapy. Arch Phys Med Rehabil 2002; 83:1501Y5 24. Jutte LS, Hawkins J, Miller KC, et al: Skinfold thickness at 8 common cryotherapy sites in various athletic populations. J Athl Train 2012;47:170Y7 25. Bischoff C, Stalberg E, Falck B, et al: Reference values of motor unit action potentials obtained with multi-MUAP analysis. Muscle Nerve 1994;17: 842Y51 26. Chu J, Takehara I, Li TC, et al: Skill and selection bias has least influence on motor unit action potential firing rate/frequency. Electromyogr Clin Neurophysiol 2003;43:387Y92

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Effects of ethyl chloride spray on pain and parameters of needle electromyography in the upper extremity.

The aim of this study was to compare the effects of ethyl chloride and placebo sprays for reducing pain induced by needle electromyography and changes...
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