Journal of Clinical Neuroscience xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Case study
Does transcutaneous nerve stimulation have effect on sympathetic skin response? E. Esra Okuyucu a, Aysße Dicle Turhanog˘lu b, Murat Guntel c,⇑, Serkan Yılmazer d, Nazan Savasß e, Ayhan Mansurog˘lu f a
Mustafa Kemal University, Department of Neurology, Hatay, Turkey Mustafa Kemal University, Department of Physiotherapy and Rehabilitation, Hatay, Turkey Elazıg˘ Education and Research Hospital, Department of Neurology, Elazıg˘, Turkey d Private East Mediterranean Hospital, Department of Neurology, Hatay, Turkey e Mustafa Kemal University, Department of Public Health, Hatay, Turkey f Private Southpark Hospital, Department of Physiotherapy and Rehabilitation, Hatay, Turkey b c
a r t i c l e
i n f o
Article history: Received 29 April 2017 Accepted 10 August 2017 Available online xxxx Keywords: Sympathetic skin response Transcutaneous nerve stimulation Electrophysiolgy
a b s t r a c t Objective: This study examined the effects of transcutaneous electrical nerve stimulation (TENS) on the sympathetic nerve system by sympathetic skin response test. Methods: Fifty-five healthy volunteers received either: (i) 30 minutes TENS (25 participants) (ii) 30 minutes sham TENS (30 participants) and SSR test was performed pre- and post-TENS. The mean values of latency and peak-to-peak amplitude of five consecutive SSRs were calculated. Results: A significant amplitude difference was found between TENS and sham TENS group both in right and left hand (p = 0.04, p = 0.01, respectively). However there was no significant latancy difference between two groups (p>0.05 ). Conclusion: TENS has an inhibitory effect on elicited SNS responses when compared with sham TENS control group. Ó 2017 Elsevier Ltd. All rights reserved.
1. Introduction Sympathetic skin response (SSR), a diagnostic test for evaluating sudomotor function, can be used to detect sympathetic sudomotor deficit and provide clues as to the integrity of the autonomic nervous system [1]. SSR, defined as the momentary change of electrical potential of the skin, can be spontaneous or reflexively evoked by different arousal stimuli [2]. The SSR is a somato-sympathetic reflex with a spinal, a bulbar, and a suprabulbar component. The polysynaptic reflex arc includes afferent sensory fibers, central relays coordinated in the posterior hypothalamus or upper brainstem reticular formation and an efferent pathway through the spinal cord, sympathetic preganglionic and postganglionic nerve fibers, with sweat glands as effectors [3]. Despite this complexity, the SSR has been used frequently, because it can be easily performed with routine electromyographic equipment. Transcutaneous electrical nerve stimulation (TENS) is defined by the American Physical Therapy Association as the application
of electrical stimulation to the skin for pain relief for a variety of pain syndromes [4]. Although its frequent use, the mechanisms by which TENS produces pain relief are still inconclusive [5]. The most commonly performed TENS modalities in clinical pain are high frequency (>50 Hz), low intensity TENS, delivered at sensory-level intensity but there is no motor contraction, and low-frequency (1–5 Hz), high intensity TENS, with stimulation intensity producing motor contraction [6]. High-frequency/lowintensity TENS is thought to interrupt the transmission of nociceptive afferent responses to the spinal cord dorsal horn by stimulating large–diameter group II myelinated afferent fibers [7]. On the other hand, low-frequency/high- intensity TENS is thought to stimulate small-diameter group III–IV unmyelinated afferent fibers and to be effective by the release of endogenous opioids in the central nervous system. The aim of this study was to investigate the effect of lowfrequency/high-intensity TENS on the sympathetic skin response. 2. Material and methods
⇑ Corresponding author at: Elazıg Education and Research Hospital Neurology Clinic, Inonu Street, 23200 Elazıg, Turkey. E-mail address: [email protected] (M. Guntel).
Fifty-five healthy volunteers were recruited for this study. None of them had a significant medical disease or of toxic habits and
https://doi.org/10.1016/j.jocn.2017.08.033 0967-5868/Ó 2017 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Okuyucu EE et al. Does transcutaneous nerve stimulation have effect on sympathetic skin response? J Clin Neurosci (2017), https://doi.org/10.1016/j.jocn.2017.08.033
2
E.E. Okuyucu et al. / Journal of Clinical Neuroscience xxx (2017) xxx–xxx
none had been taking any medication which might influence the autonomic nervous system. All subjects abstained from smoking and drinking caffeine on the day of investigation The physical examination was normal. The protocol was approved by the local Ethics Committee of the Medical Faculty, and informed consent was obtained in each case. SSR recordings were based on the technique described by Shahani et al. [1]. Volunteers lay supine and relaxed in a quiet, airconditioned, semidarkened room, maintained at a controlled temperature from 21 to 24 °C). The skin temperature of each subject was above 31 °C. Subjects were instructed to remain with their eyes open, and not to sleep, cough, sigh, laugh, breathe deeply, talk or move their head during the procedure. SSR test was carried out between 11 am and 1 pm. SSR test was performed twice, just before and after TENS administration. Active standard disk electrodes (10 mm diameter) were applied with paste to the volar (cathode) and dorsal (anode) side of the hand, bilaterally. The recordings were performed on a Medelec Synergy electromyograph. Band fast filters were set between 1 and 1000 Hz. The sensitivity was 0.5 and 1 mV. The SSRs were recorded from both hands using two channels after one pulse. Pulses in 0.1 ms duration and 30 mA intensity were applied to the skin of left wrist exciting median nerve. Five stimuli consisting of a single electrical pulse were delivered randomly every 20–25 s to avoid habituation. Subjects who showed no response on either side after receiving 10 consecutive electrical stimuli were considered unresponsive. The latency and amplitude measurements in SSR were performed manually by the cursors of the electromyograph. Latencies were measured from the beginning of the stimulus to the onset of the response from the baseline. Amplitudes were taken from the peak to peak of the recorded waves. The mean values of latency and peak-to-peak amplitude of the five consecutive SSRs were calculated. The TENS unit was Catanoga Intelect 2773 MS, USA. The electrodes were positioned on the left hand, with the negative lead placed over the ulnar edge of the hand and the positive lead on the web between the first and second metatarsal bones. This placement stimulates the radial and ulnar nerves that supply all the sympathetic fibers to the hand and digits [8]. The first two researcher who studied in the electrophysiology laboratory were blinded about the application of TENS. Subject in TENS group were told that they would feel ‘‘tapping sensation” and might have muscle contractions around their thumb, finger. The intensity was increased until it reached maximum tolerable level for the subject. In the sham TENS condition, TENS unit attached but the machine would not be switched on. So no current was applied. Subjects were told that in this form of TENS, they may or may not feel a sensation. TENS were applied for 30 min for each subject and at the end of TENS, SSR test was performed again by blinded another experimenter. Data were analyzed by SPSS software package (version 11.5). Results are expressed as the mean ± SD. Data were evaluated statistically using Wilcoxon test, Paired T test, Mann Whitney U test
Table 1 The mean amplitude values of SSRs in TENS and shamTENS group among pre-and post-stimulation. TENS group (n = 25) mean ± SD
Sham TENS group (n = 30) mean ± SD
Right Hand Pre-TENS Amplitude Post-TENS Amplitude
5611.70 ± 3543.45 3627.44 ± 3131.80
4674.93 ± 3271.71 4379.57 ± 3274.23
Left Hand Pre-TENS Amplitude Post-TENS Amplitude
6068.94 ± 3633.70 3923.44 ± 2706.46
5386.54 ± 3826.73 4504.57 ± 3274.23
Table 2 The comparement of latancy and amplitude difference of TENS and sham TENS group among pre- and post-stimulation.
*
TENS group (n = 25) mean ± SD
Sham TENS group (n = 30) mean ± SD
P*
Left Hand Latans difference Amplitude difference
0.12 ± 0.26 2145 ± 2122.36
0.12 ± 0.28 881.96 ± 284
0.956 0.040
Right Hand Latans difference Amplitude difference
0.09 ± 0.28 1984.2 ± 2508.3
0.57 ± 0.31 295.3 ± 2353
0.606 0.013
Mann Whitney U Test.
and Kolmogorov Smirnov test, p < 0.05 was considered statistically significant. 3. Results There were 25 healthy volunteers in TENS group and 30 volunteers in sham TENS group. The mean ages of TENS group and control group were 33.12 ± 4.84 years and 29.80 ± 8.7 years, respectively (p > 0.05). The gender distributions of the two groups were also found to be comparable (p > 0.05). The mean amplitude values of SSRs were summarized in Table 1. The difference in the amplitude values of TENS group’s SSR potentials were compared to the sham TENS group among the pre and post TENS. Student’s t test on these data showed a highly significant amplitude difference between groups both in left hand and right hand (p = 0.04, p = 0.01, respectively). However there was no significant latans difference between two groups (p > 0.05). The amplitude and latans difference were summarized in Table 2. 4. Discussion The results of this study illustrate the reduction in the SSR due to TENS and emphasise the inhibitory effects of TENS on the sympathetic nervous system. The SSR assesses the integrity of the sudomotor fibres. The polysynaptic reflex arc includes afferent sensory fibres, central relays co-ordinated in the posterior hypothalamus or upper brainstem reticular formation and an efferent pathway through the spinal cord, sympathetic preganglionic and postganglionic nerve fibres, with sweat glands as effectors. Absence or delaying of the SSR may be caused by afferent or efferent volley [3]. SSR is simple, fast and easily obtainable on most electrophysiological equipment, however it might be hard to re-create and obtain steadily. As SSR amplitude is variable, some investigators do not take into account SSR amplitude measurement as a dependable parameter [3]. But, many authors consider SSR amplitude, either the largest amplitude or the mean amplitude of four consecutive SSRs [9]. In our study, we thought that the mean amplitude of five consecutive SSRs was the most dependable measurement of SSR amplitude [10]. Overall, latency measurement of SSR are of narrow value, the efferent unmyelinated fibers accounting for most of the latency may cause pertinent changes. Latency and amplitude datas of hands and/or feet SSR should be obtainable in EMG laboratories, but still the main clinical consideration remains the presence/absence of the response [2]. In our study, we considered SSR amplitude, latance and amplitude difference among pre and post TENS. The sympathetic nervous system (SNS) plays a prominent role in mediating pain [11]. Whether TENS produces analgesia through its consequences on the SNS is remained still unclear. There is a relationship anatomically between sensory afferent pain fibers
Please cite this article in press as: Okuyucu EE et al. Does transcutaneous nerve stimulation have effect on sympathetic skin response? J Clin Neurosci (2017), https://doi.org/10.1016/j.jocn.2017.08.033
E.E. Okuyucu et al. / Journal of Clinical Neuroscience xxx (2017) xxx–xxx
and sympathetic fibers. They travel parallel paths in the central nervous system. Pain fibers might also move swiftly through sympathetic ganglia en route to the spinal cord [12]. Abram et al. and Ebersold et al. have tried to relate analgesic effects of TENS and autonomic nervous system activity [13,14]. According to Abram et al., TENS may block sympathetic activity ‘‘ peripherally or centrally” in some patients and this sympathetic blockade may be responsible for the analgesia. But in their study there were statistical, methodological problems like lack of controls, unpresence of clear stimulation parameters, inconvenient statistical information [13]. Ebersold et al. investigated the effects of TENS on several different measures of autonomic nervous system activity [14]. However they failed to find any effect of TENS on their measures of autonomic function, except for reduction in skin impedance. Among the methodological problems with Ebersold’s study were the limited number of participants, subjectively evaluatedinconclusive SNS responses and inappropriate statistical analyses. Thus, firm conclusion cannot be drawn just like Abram’s study. Reeves et al. examined whether TENS analgesia is related to its effects on the sympathetic nervous system [15]. They conclude that there was no support for TENS affecting either SNS function or acute experimental pain perception. Reeves et al.’s results were consistent with some other investigators who failed to show that TENS exert inhibitory effects on SNS [14,16,17]. Several investigators have shown TENS to decrease sympathetic tone [18,19], while some others have found increased sympathetic tone [20]. The methodological variations, lack of appropriate control groups and TENS stimulation parameters were responsible from the different results of these studies. In our study, we found specific inhibitory effect of TENS on the SNS responses. According to our results, our opinion is similar with Sanderson’s; TENS may have an effect on reflexes involving autonomous nerve system and perhaps it may reduce SNS activity by interfering or/and blocking a reflex response within the spinal cord [21]. Hollman and Morgan were reported that the inhibitory effect of high-frequency/low-intensity TENS on SNS was more prominent when the sympathetic nerves were stimulated when participants were at rest [22]. They concluded that the central transmission of neuronal responses through group III and IV afferent fibers might be modulated by afferent impulse converging on the same spinal level [22]. In our study, we found decrease in amplitudes of SSRs on either the contra- or ipsilateral stimulation side. So we hypothesized that TENS does exert inhibitory effects on the SNS both near and far from the site of stimulation. Similiar to the present investigation, Olyaei et al. found that TENS inhibits the sympathetic nerve activity in healthy humans [23]. In contrast, Tracy et al. hypothesized that low-frequency TENS applied at the intensity high enough to cause motor contractions increases blood flow into this stimulated areas by the metabolic demands of contracted muscles, not through its direct effects on SNS [24]. Chen et al. reported that TENS stimulates the peripheral sensory nerves below the electrodes, and causing the release of substance P from nerve endings. According to them, substance P triggers localized vasodilation. In our opinion, TENS affected the SNS, this is a widespread and important effect so it must not be explained by a simple effect localized to the placement of TENS electrodes.
3
In conclusion, low-frequency/high-intensity TENS has an inhibitory effect on elicited SNS responses when compared with sham TENS control group. Further research is needed to firm clear conclusions. References [1] Shahani BT, Halperin JJ, Boulu P, Cohen J. Sympathetic skin response- a method of assessing unmyelinated axon dysfunction in peripheral neuropathies. J Neurol Neurosurg Psychiatry 1984;47:536–42. [2] Vetrugno R, Liguori R, Cortelli P, Montagna P. Sympathetic skin response. Clin Auton Res 2003;13:256–70. [3] Uncini A, Pullmann SL, Lovelace RE, Gambi D. The sympathetic skin response: normal values, elucidation of afferent components and application limits. J Neurol Sci 1988;87:299–306. [4] Sluka KA. Walsh. Transcutaneous electrical nerve stimulation: basic science mechanisms and clinical effectiveness. J Pain 2003;4(3):109–21. [5] Carroll D, Moore RA, McQuay HJ, Fairman F, Tramer M, Leijon G. Transcutaneous electrical nerve stimulation (TENS) for chronic pain (Cochrane Review). In: The Cochrane Library, Issue 3, Oxford: Updated software; 2003. [6] White PF, Li S, Chiu JW. Electroanalgesia: Its role in acute and chronic pain management. Anasth Analg 2001;92:505–13. [7] Melzack R, Wall PD. Pain mechanisms: a new theory. Science 1965;150:971–9. [8] Mannheimer JS, Lampe GN. Clinical transcutaneous electrical nerve stimulation. Philadelphia, PA: F.A. Davis Company; 1984. [9] Baba M, Watahiki Y, Matsunaga M, Takebe K. Sympathetic skin response in healthy man. Electromyogr Clin Neurophysiol 1988;28:277–83. [10] Elie B, Guiheneuc P. Sympathetic skin response: normal results in different experimental conditions. Electroencephalogr Clin Neurophysiol 1990;76:258–67. [11] Janig W. The sympathetic nervous system and pain. Eur J Anaesthesiol 1995;10:53–60. [12] Janig W. The sympathetic nervous system in pain: physiology and pathophysiology. In: Stanton-Hicks M, editor. Pain and the sympathetic nervous system. Boston, MA: Kluwer Academic Publications; 1990. p. 17–89. [13] Abram SE, Asiddao CB, Reynolds AC. Increased skin temperature during transcutaneous electrical stimulation. Anesth Analg 1980;59:22–5. [14] Ebersold MJ, Laws Jr ER, Albers JW. Measurements of autonomic function before, during, and after transcutaneous stimulation in patients with chronic pain and in control subjects. Mayo Clin Proc 1977;52:228–32. [15] Reeves JL, Graff-Radford SB, Shipman D. The effects of transcutaneous electrical nerve stimulation on experimental pain and sympathetic nervous system response. Pain Med 2004;5(2):150–61. [16] Johnson MI, Hajela VK, Ashton CH, Thompson J. The effects of auricular transcutaneous electrical nerve stimulation (TENS) on experimental pain threshold and autonomic function in healthy subjects. Pain 1991;46:337–42. [17] Nolan MF, Hartsfield Jr JK, Witters DM, Watson PJ. Failure of transcutaneous electrical nerve stimulation in conventional and burst modes to alter digital skin temperature. Arch Phys Med Rehabil 1993;74:182–7. [18] Cramp AF, Gilsenan C, Lowe AS, Walsh DM. The effect of high- and lowfrequency transcutaneous electrical nerve stimulation upon cutaneous blood flow and skin temperature in healthy subjects. Clin Physiol 2000;20:150–7. [19] Ernst M, Lee MH. Sympathetic effects of manual and electrical acupuncture of the Tsusanli knee point: comparison with the Hoku hand point sympathetic effects. Exp Neurol 1986;94:1–10. [20] Casale R, Gibellini R, Bozzi M, Bonelli S. Changes in sympathetic activity during high frequency T.E.N.S.. Acupunct Electrother Res 1985;10:169–75. [21] Sanderson JE, Tomlinson B, Lau MS, So KW, Cheung AH, Critchley JA, Wook KS. The effect of transcutaneous electrical nerve stimulation (TENS) on autonomic cardiovascular reflexes. Clin Auton Res 1995;5:81–4. [22] Hollman JE, Morgan BJ. Effect of transcutaneous electrical nerve stimulation on the pressor response to static handgrip exercise. Phys Ther 1997;77:28–36. [23] Olyaei GR, Talebian S, Hadian MR, Bagheri H, Momadied F. The effect of transcutaneous electrical nerve stimulation on sympathetic skin response. Electromyogr Clin Neurophysiol 2004;44(1):23–8. [24] Tracy JE, Currier DP, Threlkeld AJ. Comparison of selected pulse frequencies from two different electrical stimulators on blood flow in healthy subjects. Phys Ther 1988;68:1526–32.
Please cite this article in press as: Okuyucu EE et al. Does transcutaneous nerve stimulation have effect on sympathetic skin response? J Clin Neurosci (2017), https://doi.org/10.1016/j.jocn.2017.08.033
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Case study
Does transcutaneous nerve stimulation have effect on sympathetic skin response? E. Esra Okuyucu a, Aysße Dicle Turhanog˘lu b, Murat Guntel c,⇑, Serkan Yılmazer d, Nazan Savasß e, Ayhan Mansurog˘lu f a
Mustafa Kemal University, Department of Neurology, Hatay, Turkey Mustafa Kemal University, Department of Physiotherapy and Rehabilitation, Hatay, Turkey Elazıg˘ Education and Research Hospital, Department of Neurology, Elazıg˘, Turkey d Private East Mediterranean Hospital, Department of Neurology, Hatay, Turkey e Mustafa Kemal University, Department of Public Health, Hatay, Turkey f Private Southpark Hospital, Department of Physiotherapy and Rehabilitation, Hatay, Turkey b c
a r t i c l e
i n f o
Article history: Received 29 April 2017 Accepted 10 August 2017 Available online xxxx Keywords: Sympathetic skin response Transcutaneous nerve stimulation Electrophysiolgy
a b s t r a c t Objective: This study examined the effects of transcutaneous electrical nerve stimulation (TENS) on the sympathetic nerve system by sympathetic skin response test. Methods: Fifty-five healthy volunteers received either: (i) 30 minutes TENS (25 participants) (ii) 30 minutes sham TENS (30 participants) and SSR test was performed pre- and post-TENS. The mean values of latency and peak-to-peak amplitude of five consecutive SSRs were calculated. Results: A significant amplitude difference was found between TENS and sham TENS group both in right and left hand (p = 0.04, p = 0.01, respectively). However there was no significant latancy difference between two groups (p>0.05 ). Conclusion: TENS has an inhibitory effect on elicited SNS responses when compared with sham TENS control group. Ó 2017 Elsevier Ltd. All rights reserved.
1. Introduction Sympathetic skin response (SSR), a diagnostic test for evaluating sudomotor function, can be used to detect sympathetic sudomotor deficit and provide clues as to the integrity of the autonomic nervous system [1]. SSR, defined as the momentary change of electrical potential of the skin, can be spontaneous or reflexively evoked by different arousal stimuli [2]. The SSR is a somato-sympathetic reflex with a spinal, a bulbar, and a suprabulbar component. The polysynaptic reflex arc includes afferent sensory fibers, central relays coordinated in the posterior hypothalamus or upper brainstem reticular formation and an efferent pathway through the spinal cord, sympathetic preganglionic and postganglionic nerve fibers, with sweat glands as effectors [3]. Despite this complexity, the SSR has been used frequently, because it can be easily performed with routine electromyographic equipment. Transcutaneous electrical nerve stimulation (TENS) is defined by the American Physical Therapy Association as the application
of electrical stimulation to the skin for pain relief for a variety of pain syndromes [4]. Although its frequent use, the mechanisms by which TENS produces pain relief are still inconclusive [5]. The most commonly performed TENS modalities in clinical pain are high frequency (>50 Hz), low intensity TENS, delivered at sensory-level intensity but there is no motor contraction, and low-frequency (1–5 Hz), high intensity TENS, with stimulation intensity producing motor contraction [6]. High-frequency/lowintensity TENS is thought to interrupt the transmission of nociceptive afferent responses to the spinal cord dorsal horn by stimulating large–diameter group II myelinated afferent fibers [7]. On the other hand, low-frequency/high- intensity TENS is thought to stimulate small-diameter group III–IV unmyelinated afferent fibers and to be effective by the release of endogenous opioids in the central nervous system. The aim of this study was to investigate the effect of lowfrequency/high-intensity TENS on the sympathetic skin response. 2. Material and methods
⇑ Corresponding author at: Elazıg Education and Research Hospital Neurology Clinic, Inonu Street, 23200 Elazıg, Turkey. E-mail address: [email protected] (M. Guntel).
Fifty-five healthy volunteers were recruited for this study. None of them had a significant medical disease or of toxic habits and
https://doi.org/10.1016/j.jocn.2017.08.033 0967-5868/Ó 2017 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Okuyucu EE et al. Does transcutaneous nerve stimulation have effect on sympathetic skin response? J Clin Neurosci (2017), https://doi.org/10.1016/j.jocn.2017.08.033
2
E.E. Okuyucu et al. / Journal of Clinical Neuroscience xxx (2017) xxx–xxx
none had been taking any medication which might influence the autonomic nervous system. All subjects abstained from smoking and drinking caffeine on the day of investigation The physical examination was normal. The protocol was approved by the local Ethics Committee of the Medical Faculty, and informed consent was obtained in each case. SSR recordings were based on the technique described by Shahani et al. [1]. Volunteers lay supine and relaxed in a quiet, airconditioned, semidarkened room, maintained at a controlled temperature from 21 to 24 °C). The skin temperature of each subject was above 31 °C. Subjects were instructed to remain with their eyes open, and not to sleep, cough, sigh, laugh, breathe deeply, talk or move their head during the procedure. SSR test was carried out between 11 am and 1 pm. SSR test was performed twice, just before and after TENS administration. Active standard disk electrodes (10 mm diameter) were applied with paste to the volar (cathode) and dorsal (anode) side of the hand, bilaterally. The recordings were performed on a Medelec Synergy electromyograph. Band fast filters were set between 1 and 1000 Hz. The sensitivity was 0.5 and 1 mV. The SSRs were recorded from both hands using two channels after one pulse. Pulses in 0.1 ms duration and 30 mA intensity were applied to the skin of left wrist exciting median nerve. Five stimuli consisting of a single electrical pulse were delivered randomly every 20–25 s to avoid habituation. Subjects who showed no response on either side after receiving 10 consecutive electrical stimuli were considered unresponsive. The latency and amplitude measurements in SSR were performed manually by the cursors of the electromyograph. Latencies were measured from the beginning of the stimulus to the onset of the response from the baseline. Amplitudes were taken from the peak to peak of the recorded waves. The mean values of latency and peak-to-peak amplitude of the five consecutive SSRs were calculated. The TENS unit was Catanoga Intelect 2773 MS, USA. The electrodes were positioned on the left hand, with the negative lead placed over the ulnar edge of the hand and the positive lead on the web between the first and second metatarsal bones. This placement stimulates the radial and ulnar nerves that supply all the sympathetic fibers to the hand and digits [8]. The first two researcher who studied in the electrophysiology laboratory were blinded about the application of TENS. Subject in TENS group were told that they would feel ‘‘tapping sensation” and might have muscle contractions around their thumb, finger. The intensity was increased until it reached maximum tolerable level for the subject. In the sham TENS condition, TENS unit attached but the machine would not be switched on. So no current was applied. Subjects were told that in this form of TENS, they may or may not feel a sensation. TENS were applied for 30 min for each subject and at the end of TENS, SSR test was performed again by blinded another experimenter. Data were analyzed by SPSS software package (version 11.5). Results are expressed as the mean ± SD. Data were evaluated statistically using Wilcoxon test, Paired T test, Mann Whitney U test
Table 1 The mean amplitude values of SSRs in TENS and shamTENS group among pre-and post-stimulation. TENS group (n = 25) mean ± SD
Sham TENS group (n = 30) mean ± SD
Right Hand Pre-TENS Amplitude Post-TENS Amplitude
5611.70 ± 3543.45 3627.44 ± 3131.80
4674.93 ± 3271.71 4379.57 ± 3274.23
Left Hand Pre-TENS Amplitude Post-TENS Amplitude
6068.94 ± 3633.70 3923.44 ± 2706.46
5386.54 ± 3826.73 4504.57 ± 3274.23
Table 2 The comparement of latancy and amplitude difference of TENS and sham TENS group among pre- and post-stimulation.
*
TENS group (n = 25) mean ± SD
Sham TENS group (n = 30) mean ± SD
P*
Left Hand Latans difference Amplitude difference
0.12 ± 0.26 2145 ± 2122.36
0.12 ± 0.28 881.96 ± 284
0.956 0.040
Right Hand Latans difference Amplitude difference
0.09 ± 0.28 1984.2 ± 2508.3
0.57 ± 0.31 295.3 ± 2353
0.606 0.013
Mann Whitney U Test.
and Kolmogorov Smirnov test, p < 0.05 was considered statistically significant. 3. Results There were 25 healthy volunteers in TENS group and 30 volunteers in sham TENS group. The mean ages of TENS group and control group were 33.12 ± 4.84 years and 29.80 ± 8.7 years, respectively (p > 0.05). The gender distributions of the two groups were also found to be comparable (p > 0.05). The mean amplitude values of SSRs were summarized in Table 1. The difference in the amplitude values of TENS group’s SSR potentials were compared to the sham TENS group among the pre and post TENS. Student’s t test on these data showed a highly significant amplitude difference between groups both in left hand and right hand (p = 0.04, p = 0.01, respectively). However there was no significant latans difference between two groups (p > 0.05). The amplitude and latans difference were summarized in Table 2. 4. Discussion The results of this study illustrate the reduction in the SSR due to TENS and emphasise the inhibitory effects of TENS on the sympathetic nervous system. The SSR assesses the integrity of the sudomotor fibres. The polysynaptic reflex arc includes afferent sensory fibres, central relays co-ordinated in the posterior hypothalamus or upper brainstem reticular formation and an efferent pathway through the spinal cord, sympathetic preganglionic and postganglionic nerve fibres, with sweat glands as effectors. Absence or delaying of the SSR may be caused by afferent or efferent volley [3]. SSR is simple, fast and easily obtainable on most electrophysiological equipment, however it might be hard to re-create and obtain steadily. As SSR amplitude is variable, some investigators do not take into account SSR amplitude measurement as a dependable parameter [3]. But, many authors consider SSR amplitude, either the largest amplitude or the mean amplitude of four consecutive SSRs [9]. In our study, we thought that the mean amplitude of five consecutive SSRs was the most dependable measurement of SSR amplitude [10]. Overall, latency measurement of SSR are of narrow value, the efferent unmyelinated fibers accounting for most of the latency may cause pertinent changes. Latency and amplitude datas of hands and/or feet SSR should be obtainable in EMG laboratories, but still the main clinical consideration remains the presence/absence of the response [2]. In our study, we considered SSR amplitude, latance and amplitude difference among pre and post TENS. The sympathetic nervous system (SNS) plays a prominent role in mediating pain [11]. Whether TENS produces analgesia through its consequences on the SNS is remained still unclear. There is a relationship anatomically between sensory afferent pain fibers
Please cite this article in press as: Okuyucu EE et al. Does transcutaneous nerve stimulation have effect on sympathetic skin response? J Clin Neurosci (2017), https://doi.org/10.1016/j.jocn.2017.08.033
E.E. Okuyucu et al. / Journal of Clinical Neuroscience xxx (2017) xxx–xxx
and sympathetic fibers. They travel parallel paths in the central nervous system. Pain fibers might also move swiftly through sympathetic ganglia en route to the spinal cord [12]. Abram et al. and Ebersold et al. have tried to relate analgesic effects of TENS and autonomic nervous system activity [13,14]. According to Abram et al., TENS may block sympathetic activity ‘‘ peripherally or centrally” in some patients and this sympathetic blockade may be responsible for the analgesia. But in their study there were statistical, methodological problems like lack of controls, unpresence of clear stimulation parameters, inconvenient statistical information [13]. Ebersold et al. investigated the effects of TENS on several different measures of autonomic nervous system activity [14]. However they failed to find any effect of TENS on their measures of autonomic function, except for reduction in skin impedance. Among the methodological problems with Ebersold’s study were the limited number of participants, subjectively evaluatedinconclusive SNS responses and inappropriate statistical analyses. Thus, firm conclusion cannot be drawn just like Abram’s study. Reeves et al. examined whether TENS analgesia is related to its effects on the sympathetic nervous system [15]. They conclude that there was no support for TENS affecting either SNS function or acute experimental pain perception. Reeves et al.’s results were consistent with some other investigators who failed to show that TENS exert inhibitory effects on SNS [14,16,17]. Several investigators have shown TENS to decrease sympathetic tone [18,19], while some others have found increased sympathetic tone [20]. The methodological variations, lack of appropriate control groups and TENS stimulation parameters were responsible from the different results of these studies. In our study, we found specific inhibitory effect of TENS on the SNS responses. According to our results, our opinion is similar with Sanderson’s; TENS may have an effect on reflexes involving autonomous nerve system and perhaps it may reduce SNS activity by interfering or/and blocking a reflex response within the spinal cord [21]. Hollman and Morgan were reported that the inhibitory effect of high-frequency/low-intensity TENS on SNS was more prominent when the sympathetic nerves were stimulated when participants were at rest [22]. They concluded that the central transmission of neuronal responses through group III and IV afferent fibers might be modulated by afferent impulse converging on the same spinal level [22]. In our study, we found decrease in amplitudes of SSRs on either the contra- or ipsilateral stimulation side. So we hypothesized that TENS does exert inhibitory effects on the SNS both near and far from the site of stimulation. Similiar to the present investigation, Olyaei et al. found that TENS inhibits the sympathetic nerve activity in healthy humans [23]. In contrast, Tracy et al. hypothesized that low-frequency TENS applied at the intensity high enough to cause motor contractions increases blood flow into this stimulated areas by the metabolic demands of contracted muscles, not through its direct effects on SNS [24]. Chen et al. reported that TENS stimulates the peripheral sensory nerves below the electrodes, and causing the release of substance P from nerve endings. According to them, substance P triggers localized vasodilation. In our opinion, TENS affected the SNS, this is a widespread and important effect so it must not be explained by a simple effect localized to the placement of TENS electrodes.
3
In conclusion, low-frequency/high-intensity TENS has an inhibitory effect on elicited SNS responses when compared with sham TENS control group. Further research is needed to firm clear conclusions. References [1] Shahani BT, Halperin JJ, Boulu P, Cohen J. Sympathetic skin response- a method of assessing unmyelinated axon dysfunction in peripheral neuropathies. J Neurol Neurosurg Psychiatry 1984;47:536–42. [2] Vetrugno R, Liguori R, Cortelli P, Montagna P. Sympathetic skin response. Clin Auton Res 2003;13:256–70. [3] Uncini A, Pullmann SL, Lovelace RE, Gambi D. The sympathetic skin response: normal values, elucidation of afferent components and application limits. J Neurol Sci 1988;87:299–306. [4] Sluka KA. Walsh. Transcutaneous electrical nerve stimulation: basic science mechanisms and clinical effectiveness. J Pain 2003;4(3):109–21. [5] Carroll D, Moore RA, McQuay HJ, Fairman F, Tramer M, Leijon G. Transcutaneous electrical nerve stimulation (TENS) for chronic pain (Cochrane Review). In: The Cochrane Library, Issue 3, Oxford: Updated software; 2003. [6] White PF, Li S, Chiu JW. Electroanalgesia: Its role in acute and chronic pain management. Anasth Analg 2001;92:505–13. [7] Melzack R, Wall PD. Pain mechanisms: a new theory. Science 1965;150:971–9. [8] Mannheimer JS, Lampe GN. Clinical transcutaneous electrical nerve stimulation. Philadelphia, PA: F.A. Davis Company; 1984. [9] Baba M, Watahiki Y, Matsunaga M, Takebe K. Sympathetic skin response in healthy man. Electromyogr Clin Neurophysiol 1988;28:277–83. [10] Elie B, Guiheneuc P. Sympathetic skin response: normal results in different experimental conditions. Electroencephalogr Clin Neurophysiol 1990;76:258–67. [11] Janig W. The sympathetic nervous system and pain. Eur J Anaesthesiol 1995;10:53–60. [12] Janig W. The sympathetic nervous system in pain: physiology and pathophysiology. In: Stanton-Hicks M, editor. Pain and the sympathetic nervous system. Boston, MA: Kluwer Academic Publications; 1990. p. 17–89. [13] Abram SE, Asiddao CB, Reynolds AC. Increased skin temperature during transcutaneous electrical stimulation. Anesth Analg 1980;59:22–5. [14] Ebersold MJ, Laws Jr ER, Albers JW. Measurements of autonomic function before, during, and after transcutaneous stimulation in patients with chronic pain and in control subjects. Mayo Clin Proc 1977;52:228–32. [15] Reeves JL, Graff-Radford SB, Shipman D. The effects of transcutaneous electrical nerve stimulation on experimental pain and sympathetic nervous system response. Pain Med 2004;5(2):150–61. [16] Johnson MI, Hajela VK, Ashton CH, Thompson J. The effects of auricular transcutaneous electrical nerve stimulation (TENS) on experimental pain threshold and autonomic function in healthy subjects. Pain 1991;46:337–42. [17] Nolan MF, Hartsfield Jr JK, Witters DM, Watson PJ. Failure of transcutaneous electrical nerve stimulation in conventional and burst modes to alter digital skin temperature. Arch Phys Med Rehabil 1993;74:182–7. [18] Cramp AF, Gilsenan C, Lowe AS, Walsh DM. The effect of high- and lowfrequency transcutaneous electrical nerve stimulation upon cutaneous blood flow and skin temperature in healthy subjects. Clin Physiol 2000;20:150–7. [19] Ernst M, Lee MH. Sympathetic effects of manual and electrical acupuncture of the Tsusanli knee point: comparison with the Hoku hand point sympathetic effects. Exp Neurol 1986;94:1–10. [20] Casale R, Gibellini R, Bozzi M, Bonelli S. Changes in sympathetic activity during high frequency T.E.N.S.. Acupunct Electrother Res 1985;10:169–75. [21] Sanderson JE, Tomlinson B, Lau MS, So KW, Cheung AH, Critchley JA, Wook KS. The effect of transcutaneous electrical nerve stimulation (TENS) on autonomic cardiovascular reflexes. Clin Auton Res 1995;5:81–4. [22] Hollman JE, Morgan BJ. Effect of transcutaneous electrical nerve stimulation on the pressor response to static handgrip exercise. Phys Ther 1997;77:28–36. [23] Olyaei GR, Talebian S, Hadian MR, Bagheri H, Momadied F. The effect of transcutaneous electrical nerve stimulation on sympathetic skin response. Electromyogr Clin Neurophysiol 2004;44(1):23–8. [24] Tracy JE, Currier DP, Threlkeld AJ. Comparison of selected pulse frequencies from two different electrical stimulators on blood flow in healthy subjects. Phys Ther 1988;68:1526–32.
Please cite this article in press as: Okuyucu EE et al. Does transcutaneous nerve stimulation have effect on sympathetic skin response? J Clin Neurosci (2017), https://doi.org/10.1016/j.jocn.2017.08.033
