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Adjusting Pulse Amplitude During Transcutaneous Electrical Nerve Stimulation (TENS) Application Produces Greater Hypoalgesia
The Journal of Pain, Vol 12, No 5 (May), 2011: pp 581-590 Available online at www.sciencedirect.com
Adjusting Pulse Amplitude During Transcutaneous Electrical Nerve Stimulation (TENS) Application Produces Greater Hypoalgesia Manuela A. Pantale~ ao,* Marjorie F. Laurino,* Natalie L. G. Gallego,* Cristina M. N. Cabral,* Barbara Rakel,y Carol Vance,z Kathleen A. Sluka,z Deirdre M. Walsh,x and Richard E. Liebano* * University of the City of Sao Paulo (UNICID), Physical Therapy Department, Sao Paulo, Brazil. y College of Nursing, Graduate Program in Physical Therapy & Rehabilitation Science, University of Iowa, Iowa City, Iowa. z College of Medicine, Graduate Program in Physical Therapy & Rehabilitation Science, University of Iowa, Iowa City, Iowa. x University of Ulster, Health and Rehabilitation Sciences Research Institute, Newtownabbey, Northern Ireland, UK.
Abstract: Transcutaneous electrical nerve stimulation (TENS) is a noninvasive technique used for pain modulation. During application of TENS there is a fading of current sensation. Textbooks of electrophysical agents recommend that pulse amplitude should be constantly adjusted. This seems to be accepted clinically despite the fact that there is no direct experimental evidence. The aim of the current study was to investigate the hypoalgesic effect of adjusting TENS pulse amplitude on pressure pain thresholds (PPTs) in healthy humans. Fifty-six healthy TENS na€ıve participants were recruited and randomly assigned to 1 of 4 groups (n = 14 per group): control, placebo TENS, fixed pulse amplitude TENS, and adjusted pulse amplitude TENS. Both active and placebo TENS were applied to the dominant forearm. PPTs were recorded from 2 points on the dominant forearm and hand before, during, and after 40 minutes of TENS. TENS increased the PPTs on the forearm (P = .003) and hand (P = .003) in the group that received the adjusted pulse amplitude when compared to all other groups. The mean final pulse amplitude for the adjusted pulse amplitude TENS group was 35.51 mA when compared to the fixed pulse amplitude TENS group, which averaged 31.37 mA (P = .0318). Perspective: These results suggest that it is important to adjust the pulse amplitude during TENS application to get the maximal analgesic effect. We propose that the fading of current sensation allows the use of higher pulse amplitudes, which would activate a greater number of and deeper tissue afferents to produce greater analgesia. ª 2011 by the American Pain Society Key words: Transcutaneous electrical nerve stimulation, pain measurement, pain threshold.
T
ranscutaneous electrical nerve stimulation (TENS) is a nonpharmacologic and noninvasive treatment commonly used by health care practitioners as an adjunct treatment for a variety of painful conditions.4,12,35 The most popular theory for the mechanism of action of TENS is the gate control theory of pain.33,44 This theory proposes that stimulation of large-diameter Received June 23, 2010; Revised October 20, 2010; Accepted November 9, 2010. Supported by the Special Olympics World Board. TENS units were donated by Empi, Inc (USA). Address reprint requests to Richard Liebano, PT, PhD, Full Professor, University of the City of Sao Paulo (UNICID), Physical Therapy Department, Rua Cesario Galeno 448/475, Tatuape, Sao Paulo, SP - CEP 03071-000. E-mail: [email protected] 1526-5900/$36.00 ª 2011 by the American Pain Society doi:10.1016/j.jpain.2010.11.001
afferent fibers (Ab) activates local inhibitory circuits in the dorsal horn of the spinal cord and prevents nociceptive impulses carried by small-diameter fibers (C and Ad) from reaching higher brain centers.44,46 Despite the clinical popularity of more than 30 years of use of TENS for the treatment of pain and an extensive research base, there is little consensus regarding the optimal parameters required to induce maximal hypoalgesic effects.8,50 During application of TENS there is a fading of current sensation.13 This phenomenon is usually attributed to adaptation, habituation, or accommodation to electrical stimulation. Adaptation is defined as a decrease in the frequency of action potentials, and a decrease in the subjective sensation of stimulation when electrical stimulation is applied when there is no change in the applied stimulus.43 Habituation occurs when electrical 581
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stimulation continues to evoke action potentials but there is a reduction in the central nervous system response.40 The term accommodation is used to refer to a rise in membrane threshold potential associated with a slowly applied depolarization current.48 For this reason, most TENS devices provide the option of modulation of current parameters to avoid these effects. In textbooks of electrophysical agents, it is recommended that stimulus intensity (pulse duration or pulse amplitude) should be constantly adjusted during treatment to prevent adaptation, accommodation, and habituation.3,5,31,47,49 This seems to be accepted despite the fact that there is no direct experimental evidence. Defrin et al13 demonstrated that the fading of sensation during interferential current (IFC) treatment does not decrease the analgesic effect when treating patients with chronic pain due to knee osteoarthritis. The physical properties of IFC and TENS are quite different.42 The active element of TENS is biphasic low-frequency pulsed currents (1–200 Hz) whereas IFC is a type of medium-frequency alternating current, with carrier frequencies of 1 to 10 kHz and modulated in amplitude.25,42 Theoretically, IFC has the advantage of reducing the skin impedance normally incurred by traditional low-frequency currents and deeper penetration into tissues.7,25,37 To our knowledge, no previous experimental pain studies have systematically assessed the influence of fading of sensation on hypoalgesic effects during TENS applications. With these concerns in mind, the aim of the present investigation was to investigate the hypoalgesic effect of adjusting TENS pulse amplitude using upper limb pressure pain threshold (PPT) in healthy volunteers. A randomized placebo-controlled blinded design was used.
Methods Participants After obtaining approval from the University of the ~o Paulo’s Research Ethics Committee, 56 TENS City of Sa na€ıve healthy volunteers were recruited from the staff and students of the University (28 males, 28 females; mean age, 22 years; range 18–36 years). Participants were screened (Investigator 1) for relevant contraindications including injury or nerve damage to the upper limbs, current pain, pregnancy, chronic illness, cardiac pacemaker, epilepsy, allergies to the TENS electrodes, currently taking pain medication, skin conditions or deficient skin sensation in the areas of electrode placement. After giving informed written consent, participants were stratified by gender11,39 to ensure equal numbers of men and women in each group and randomly allocated to 1 of 4 groups (n = 14 per group): Fixed Pulse Amplitude TENS; Adjusted Pulse Amplitude TENS; Placebo TENS; and Control (Fig 1). Randomization was performed by an investigator not involved in data collection using the sequentially numbered, opaque sealed envelopes (SNOSE) allocation concealment method.15,41 The envelopes were stored in a secure cabinet that only the allocation investigator had access to and were opened immediately prior to intervention allocation.
Pulse Amplitude During TENS Application Sample size was calculated using a mean difference of 10.1 N (active TENS versus placebo TENS) and standard deviation of 6.98 N obtained from previous data on PPT and TENS.32 At a significance level of .05 and power of 80%, it was calculated that 12 participants were required in each group (Minitab, v.15; Minitab, State College, PA). Allowing for attrition, 14 participants were recruited per group.
Participant Preparation The participants were asked to remain seated in a comfortable upright position during all procedures. Participants’ upper limbs were cleaned prior to marking electrode placement and PPT recording sites using a marker. The electrode placement sites were marked out as described below. Two PPT recording sites were marked out the dominant upper limb as follows: 1) 3 cm distal to the distal end of the anatomical snuff box in the midline of the belly of the first dorsal interosseous muscle (Fig 2A); and 2) on the anterior aspect of the forearm, 7.5 cm proximal to the distal wrist crease (Fig 2B). These sites were chosen to examine the effects of TENS within (hand and forearm) the area of stimulation.
Pressure Pain Threshold Measurements PPT was recorded by Investigator 2 who was blind to group allocation using a Kratos pressure algometer (DDK, Kratos Equipments, Brazil) (Fig 2A and B). The algometer was calibrated prior to the beginning of the study. A preliminary reliability study was conducted by Investigator 2 by recording PPT from the 2 recording points described above from 10 healthy volunteers on 2 occasions, 48 hours apart.11,51 This reliability study demonstrated excellent overall between-session intrarater reliability for PPT measurements from the hand (.92) and from the forearm (.98). In the current study, Investigator 2 was kept blind to the group allocation. In addition, electrodes were applied to all participants’ forearms and the display of the TENS unit was covered during PPT measurements to conceal if active or placebo TENS was being applied. Participants’ hands and forearms were covered with a cardboard box containing 2 holes over the PPT recording points. This prevented Investigator 2 from seeing any muscle contractions during PPT measurements. During PPT recording, the circular probe of the algometer (1 cm2 area) was placed perpendicular to the skin and applied at a constant rate (approximately 5 N/s). Participants were asked to say stop when the sensation they were feeling turned to pain (distinct from pressure or discomfort). A sign was placed on the wall above the participants’ eye levels and they were asked to look at this sign during PPT recordings (text on sign = ‘‘Say STOP when you feel a sensation of pain distinct from pressure or discomfort’’). Three measurements (in N) were taken from each recording site at each time point and the average used for data analyses.10,16-19,34 The pressure in kPa was calculated using the following formula: P [Pa] = F [N]/A [m2], where P is the pressure, F is the applied force, and A is the area of the
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Figure 1. Study design and flow of participants through the study.
algometer probe. The TENS intervention was not interrupted to take PPT recordings. At the 2 recording sites, PPT was recorded at 0, 20, 40, and 60 minutes. During the study, PPT readings from the 2 recording sites were taken in a random order to avoid order bias.11,19 Randomization was performed using a computer-generated random number list compiled by an investigator not involved in data collection. This random order was concealed by writing the order onto cards and sealing them in the same opaque envelopes used for group allocation. These cards were given to Investigator 2 only after informed consent was obtained from each participant. All participants were given 2 practice demonstrations of PPT on their nondominant forearm to en-
sure they understood the concept of PPT recording before the study began.
Groups The interventions were applied to the dominant upper limb by Investigator 1 as described below.
Fixed Pulse Amplitude TENS Two 50 90 mm standard self-adhesive electrodes (ValuTrode; Axelgaard, Fallbrook, CA) were positioned on the lateral aspect of the forearm at the level of the distal wrist crease and the lateral aspect of the forearm, 10 cm proximal to the distal wrist crease (Fig 2A and B). Once TENS was applied, the pulse amplitude was gradually
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Figure 2. (A) Electrode position and location of the PPT recording point on the hand. (B) Electrode position and location of the PPT recording point on the forearm.
increased until a strong but comfortable subjective intensity was reported by the participant. The pulse amplitude was maintained at this level (ie, not adjusted at all) for the duration of the 40-minute treatment.
Adjusted Pulse Amplitude TENS Electrodes applied as above. The pulse amplitude was gradually increased until a strong but comfortable subjective intensity was reported by the participant. At 5-minute intervals, the participants were asked if the sensation had faded and the pulse amplitude was increased again to a subjective strong but comfortable intensity level.
Placebo TENS Electrodes applied as above. The sham device was a Select TENS unit (Empi, St. Paul, MN) modified to deliver a stimulus for a total of 42 seconds at a strong but comfortable intensity level (burst stimulus with 100-Hz frequency and a 5-second cycle time) after which time the current amplitude resets to 0 mA.39 Participants in this group were asked every 5 minutes if they were comfortable.
Control Electrodes applied as above and leads connected to the TENS unit but no TENS applied. The TENS units were calibrated using an oscilloscope prior to the study commencing. In the 2 active TENS groups, TENS was applied using a continuous output at 100 Hz for 40 minutes (Select TENS unit, Empi) while the participant was seated with the dominant forearm placed on a wooden table. Participants in the 2 active and placebo groups were given a demonstration of their allocated intervention on the nondominant forearm be-
fore the baseline (0 minute) PPT reading was taken. The pulse amplitude was increased to sensory threshold for this demonstration. The pulse duration of the Select TENS unit varied with the amplitude applied (range 0 to 400 ms at 50% peak amplitude). Participants in the Placebo TENS and both active TENS groups were blind to group allocation; they were told that they may or may not feel a tingling sensation. In the Control group, participants were told that they would not receive an intervention.
Pulse Amplitude The value of the pulse amplitude was calibrated for each participant. This was done by measuring the peakto-peak voltage of the waveform across a 1 kU resistor on an oscilloscope. The pulse amplitude required to produce a strong but comfortable sensation was recorded every 5 minutes for the Adjusted Pulse Amplitude TENS group.
Assessing Blinding At the end of data collection, the effectiveness of blinding was assessed by Investigator 1 asking both the participant and Investigator 2 which TENS intervention they thought was delivered with 3 options for the answer: ‘‘real,’’ ‘‘placebo,’’ or ‘‘don’t know.’’ Their responses to this question were recorded and used to gauge the adequacy of subject and investigator blinding.39
Data Analysis Data were analyzed using SPSS software (v.17; SPSS Inc; Chicago, IL) by an investigator who was blind to group allocation: an average of the 3 PPT scores recorded at each time point was used for analysis. Shapiro-Wilk tests showed that the data were normally distributed,
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Table 1. Mean 6 SEM Raw PPT Scores for All Time Points, for Each Group (n = 14 Per Group) for Hand PPT Measurements TENS APPLICATION GROUP
BASELINE
20 MIN
40 MIN
POST TENS 60 MIN
Control Placebo TENS Fixed Pulse Amplitude TENS Adjusted Pulse Amplitude TENS
244.04 6 24.25 260.49 6 28.66 220.33 6 28.81 241.57 6 24.78
237.42 6 19.07 281.59 6 30.86 250.80 6 34.83 296.21 6 28.73
237.49 6 18.09 263.06 6 23.59 241.30 6 32.43 356.34 6 37.81
229.11 6 17.53 263.52 6 26.18 217.88 6 34.16 258.89 6 23.99
NOTE. All values are expressed in kPa.
therefore parametric tests were used to analyze the data. Percentage of change (variation from baseline values) was analyzed using between-within groups ANOVA and post hoc Tukey tests. c2 test was used to compare blinding of the groups against an expected result of 50:50 blinding (ie, chance). The unpaired t test compared the final pulse amplitude applied in the Fixed Pulse Amplitude TENS group and in the Adjusted Pulse Amplitude TENS group. One-way ANOVA compared the pulse amplitudes over time in the Adjusted Pulse Amplitude TENS group. Significance was set at P < .05.
Results PPT Data Data for the raw mean (6SEM) PPT scores for all experimental groups are summarized in Tables 1 (hand measurement site) and 2 (forearm measurement site). The percentage of PPT change in the hand over the 60 minutes is summarized in Fig 3. The greatest increase in PPT was observed in the Adjusted Pulse Amplitude TENS group, representing a greater hypoalgesic effect in this group. Fig 4 shows the percentage of PPT change in the forearm over the 60 minutes. Again, the greatest increase in PPT was observed in the Adjusted Pulse Amplitude TENS group. Statistical analyses of the PPT data at the hand using between-within groups ANOVA showed significant differences: over time (P < .0001); interactive effect between time and group (P < .0001); and between groups (P = .003). Post hoc Tukey tests indicated a significant hypoalgesic effect in the Adjusted Pulse Amplitude TENS group compared with all the other groups; there was
no significant difference between any of the other groups (Control, Placebo TENS, and Fixed Pulse Amplitude) (P > .05). Post hoc tests for statistical comparison between groups at the hand are summarized in Table 3. On the forearm, analysis of PPT data showed neither significant difference over time (P = .414) nor an interactive effect between time and group (P = .601). However, there was a significant difference between groups (P = .003). Similar to the observed changes in PPT data at the hand, the Adjusted Pulse Amplitude TENS group showed a greater hypoalgesic effect when compared to the other groups. There was no significant difference between any of the other groups (Control, Placebo TENS, and Fixed Pulse Amplitude TENS) (P > .05). Post hoc tests for statistical comparison between groups at forearm are summarized in Table 4.
Pulse Amplitude Data The mean pulse amplitude used in all groups is shown in Table 5. The data showed an increase in pulse amplitude over time in the Adjusted Pulse Amplitude TENS group (P < .0001) and a significant difference between the pulse amplitude used in the Fixed Pulse Amplitude TENS and the Adjusted Pulse Amplitude TENS group at 40 minutes (unpaired t test, P = .0318).
Assessment of Blinding The pain assessor correctly identified that participants received active TENS in 35.7% (5/14) of cases in the Fixed Pulse Amplitude TENS group and in 28.6% (4/14) of the Adjusted Pulse Amplitude TENS group. In the placebo TENS group, the assessor correctly identified that participants received placebo TENS in 21.4% (3/14) of cases.
Table 2. Mean 6 SEM Raw PPT Scores for All Time Points, for Each Group (n = 14 Per Group) for Forearm PPT Measurements TENS APPLICATION GROUP
BASELINE
20 MIN
40 MIN
POST TENS 60 MIN
Control Placebo TENS Fixed Pulse Amplitude TENS Adjusted Pulse Amplitude TENS
263.79 6 21.19 308.65 6 39.22 255.66 6 37.05 269.97 6 28.60
278.77 6 22.92 292.75 6 29.98 266.80 6 39.54 354.95 6 38.43
280.68 6 25.00 293.63 6 31.17 262.69 6 38.44 338.26 6 29.55
274.78 6 25.98 304.27 6 35.75 251.45 6 36.63 317.57 6 37.68
NOTE. All values are expressed in kPa.
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Figure 3. Percentage of change in pressure pain threshold (PPT) in the hand for each experimental group (mean 6 SEM). In the Fixed Pulse Amplitude TENS group, 8 of 14 participants correctly identified that they received real TENS, 5 thought they received placebo TENS, and 1 did not know. In the Adjusted Pulse Amplitude TENS group, 10 of 14 participants correctly identified that they received real TENS, 2 thought they received placebo TENS, and 2 indicated that they did not know. However, in the placebo TENS group, only 3 of 14 participants correctly identified that they received placebo TENS, 8 thought they received real TENS, and 3 indicated that they did not know. The rate of blinding in the placebo TENS group was different than chance (random 50:50 probability) (c test, P = .0325), indicating successful participant blinding in this group.
Discussion During the application of TENS, it is frequently reported that the sensation of tingling or buzzing beneath the electrodes gradually decreases with time, even though the pulse charge remains the same.48 It is usually recommended that current amplitude or pulse duration should be constantly adjusted when the sensation decreases.3,5,13,47,49 This recommendation led the manufacturers to incorporate stimulation parameter modulation (such as frequency, pulse duration, and amplitude) in most TENS devices despite the fact that there is no experimental evidence to support this claim. The purpose of this study was to determine if the constant increase in pulse amplitude could improve the
hypoalgesic effect of TENS. The results presented herein confirm the importance of adjusting pulse amplitude during TENS application. PPTs recorded from both hand and forearm showed a significantly higher increase in the Adjusted Pulse Amplitude TENS group when compared with Fixed Pulse Amplitude TENS, Placebo TENS and Control groups. A possible explanation for this finding is that the decrease in sensation during TENS application allows the use of higher pulse amplitudes. Several studies have shown the importance of the use of high-intensity TENS stimulation for pain control in humans.1,4,8,9,35,39,52 An experimental study in rats demonstrated that large diameter primary afferent fibers from deep tissue are required for TENS-induced antihyperalgesia.38 Based on the results of the current study, we suggest that the use of higher pulse amplitudes activates a greater number of and deeper tissue afferents to produce greater hypoalgesic effect. In the Adjusted Pulse Amplitude TENS group, the final average pulse amplitude was 13.2% higher than the amplitude applied in the Fixed Pulse Amplitude TENS group. In the Select TENS unit used in the present study, the pulse duration increased (up to a maximum of 400 ms) as the pulse amplitude increased. Thus, it is reasonable to expect an even higher increase in pulse amplitude, during the 40-minute intervention, if the pulse duration was fixed. According to gate control theory of pain, the stimulation of large-diameter afferent fibers (Ab) by TENS activates local inhibitory circuits in the dorsal horn of the spinal cord and prevents nociceptive
Figure 4. Percentage of change in pressure pain threshold (PPT) in the forearm for each experimental group (mean 6 SEM).
Pantale~ao et al Table 3.
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Summary of Post Hoc Tukey Tests for Statistical Comparison Between Groups at the Hand GROUP
Control
Placebo TENS Fixed Pulse Amplitude TENS
COMPARISON GROUP
MEAN DIFFERENCE BETWEEN GROUPS
STANDARD ERROR
P VALUE
Placebo TENS Fixed Pulse Amplitude TENS Adjusted Pulse Amplitude TENS Fixed Pulse Amplitude TENS Adjusted Pulse Amplitude TENS Adjusted Pulse Amplitude TENS
5.54 6.01 27.85 .46 22.30 21.84
7.64 7.64 7.64 7.64 7.64 7.64
.886 .860 .003 1.000 .026 .030
NOTE. All values are expressed in percentage of PPT change. Bold numbers represent significant P value.
impulses carried by small-diameter fibers (C and Ad) from reaching higher brain centers.33,44,46 Considering the habituation concept, it is possible that in the Fixed Pulse Amplitude TENS group, an interruption of the activation of inhibitory circuits in the dorsal horn of the spinal cord impaired the hypoalgesic response. On the other hand, the constant increase of pulse amplitude (in the Adjusted Pulse Amplitude TENS group) could have activated a large number of large-diameter afferent fibers, keeping the activation of inhibitory interneurons in the dorsal horn for a greater period of time. Contrary to our results, a previous study using IFC in patients with chronic knee osteoarthritis showed that the fading of current sensation during treatment did not impede its analgesic effect.13 It is noteworthy that IFC is a medium-frequency alternating current, with amplitude modulated at low frequency,36 whereas TENS units deliver low-frequency pulsed currents. Moreover, these authors used an amplitude-modulated frequency (AMF) constantly ranging between 30 and 60 Hz, and assessed pain intensity using a visual analog scale (VAS), morning stiffness, range of motion, electrical pain threshold, and percentage of pain reduction. In the current study, the pulse frequency was kept constant and pressure pain thresholds were used as the outcome measure. Thus, differences in experimental design may account for these findings. As skin impedance is inversely proportional to the frequency of alternating current (AC), it has been claimed that IFC has the advantage of diminishing the impedance of the skin and subcutaneous tissues and can therefore penetrate into the deeper tissues when compared with low-frequency pulsed currents delivered by TENS devices. Although this theory has been widely reported in
the literature,6,7,20,23-28,37 to our knowledge there are no experimental studies that confirm this theory. Moreover, the theory has been questioned by some authors2,53 because skin impedance to pulsed current depends on the phase duration, not the pulse frequency. Thus, if the pulsed current has the same phase duration as the kilohertz-frequency AC, the skin impedance would be the same even if the pulse frequency is low.53 Future studies are therefore needed to clarify this proposed effect of IFC. The current study used a novel type of sham TENS unit to deliver placebo TENS that has been recently validated.39 This sham unit looked identical to the active TENS unit. It delivered a burst stimulus for 42 seconds and then the current output resets to 0 mA. The fact that the sham unit delivers electrical current for a short period of time increases the rate of participant blinding.11,39 The percentage of participants that correctly identified whether the intervention was real or placebo was 57% in the Fixed Pulse Amplitude TENS group, 71.4% in the Adjusted Pulse Amplitude TENS group, and 21.4% in the placebo TENS group. The fact that participants correctly identified the intervention more often in active groups was not surprising and it is consistent with prior research.11,14,39 Our data support this type of placebo TENS as a useful model in TENS research, as minimal hypoalgesic effects were observed and it produced a very high level of participant blinding. The decrease in sensation during TENS application has been attributed to accommodation,21,29,31,49 adaptation,13,43 and habituation.40,48 Spielholz and Nolan48 debated what was the proper term to describe the phenomenon of fading in sensation during conventional TENS. The authors propose that habituation best
Summary of Post Hoc Tukey Tests for Statistical Comparison Between Groups at the Forearm
Table 4.
GROUP Control
Placebo TENS Fixed Pulse Amplitude TENS
COMPARISON GROUP
MEAN DIFFERENCE BETWEEN GROUPS
STANDARD ERROR
P VALUE
Placebo TENS Fixed Pulse Amplitude TENS Adjusted Pulse Amplitude TENS Fixed Pulse Amplitude TENS Adjusted Pulse Amplitude TENS Adjusted Pulse Amplitude TENS
6.03 3.48 22.46 2.55 28.50 25.94
8.02 8.02 8.02 8.02 8.02 8.02
.875 .972 .035 .989 .004 .011
NOTE. All values are expressed in percentage of PPT change. Bold numbers represent significant P value.
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Table 5.
Mean 6 SEM Pulse Amplitude Applied in all Experimental Groups Over Time
GROUP
0 MIN
5 MIN
10 MIN
15 MIN
20 MIN
25 MIN
30 MIN
35 MIN
40 MIN
Control — — — — — — — — — Placebo TENS 29.05 6 1.91 — — — — — — — — Fixed Pulse 31.37 6 1.49 31.37 6 1.49 31.37 6 1.49 31.37 6 1.49 31.37 6 1.49 31.37 6 1.49 31.37 6 1.49 31.37 6 1.49 31.37 6 1.49 Amplitude TENS Adjusted Pulse 30.19 6 1.54 31.69 6 1.22 32.16 6 1.18 33.18 6 1.06 33.79 6 0.99 34.46 6 0.98 35.07 6 0.97 35.29 6 1.03 35.51 6 1.09 Amplitude TENS NOTES. All values are expressed in mA. The unpaired t test revealed a significant difference between mean pulse amplitude in the Fixed Pulse Amplitude TENS and Adjusted Pulse Amplitude TENS at 40 min (P = .0318). Over the 40 min of TENS application in the Adjusted Pulse Amplitude TENS group, there was a significant increase in pulse amplitude (1-way ANOVA, P < .0001); the final mean pulse amplitude was 19.99 6 4.16% higher than the mean pulse amplitude used at the beginning of the experiment.
describes this physiological response that results in a decrease in neurotransmitter release from afferent nerve terminals due to the inactivation of Ca11 channels in the presynaptic membrane. As a result, local interneurons and ascending projection neurons are no longer depolarized, although action potentials continue to be transmitted toward the central nervous system from primary afferent fibers.22,48 However, work from Sluka et al show continued release of neurotransmitters in the spinal cord throughout a 20-minute TENS
treatment.30,45,46 Thus, increasing amplitude to avoid habituation over the course of treatment could activate a greater number afferent fibers to enhanced neurotransmitter release in the central nervous system. In summary, the data presented here have confirmed that increasing pulse amplitude during TENS application has an important role in its hypoalgesic effect, using an experimental model of pain. Future clinical studies should be performed to confirm these results in patients experiencing pain.
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20. Fuentes CJ, Armijo-Olivo S, Magee DJ, Gross D: Does amplitude-modulated frequency have a role in the hypoalgesic response of interferential current on pressure pain sensitivity in healthy subjects? A randomised crossover study. Physiotherapy 96:22-29, 2010 21. Gersh MR: Transcutaneous electrical nerve stimulation (TENS) for management of pain and sensory patholog, in Gersh MR (ed): Electrotherapy in Rehabilitation, 1st ed. Philadelphia, PA, F.A., Davis Company, 1992, pp 149-196 22. Janko M, Trontelj JV: Transcutaneous electrical nerve stimulation: A microneurographic and perceptual study. Pain 9:219-230, 1980 23. Jarit GJ, Mohr KJ, Waller R, Glousman RE: The effects of home interferential therapy on post-operative pain, edema, and range of motion of the knee. Clin J Sport Med 13:16-20, 2003 24. Johnson MI, Tabasam G: An investigation into the analgesic effects of different frequencies of the amplitudemodulated wave of interferential current therapy on coldinduced pain in normal subjects. Arch Phys Med Rehabil 84:1387-1394, 2003 25. Johnson MI, Tabasam G: An investigation into the analgesic effects of interferential currents and transcutaneous electrical nerve stimulation on experimentally induced ischemic pain in otherwise pain-free volunteers. Phys Ther 83:208-223, 2003 26. Johnson MI, Tabasam G: A single-blind investigation into the hypoalgesic effects of different swing patterns of interferential currents on cold-induced pain in healthy volunteers. Arch Phys Med Rehabil 84:350-357, 2003 27. Johnson MI, Tabasam G: A single-blind placebo-controlled investigation into the analgesic effects of interferential currents on experimentally induced ischaemic pain in healthy subjects. Clin Physiol Funct Imaging 22:187-196, 2002 28. Jorge S, Parada CA, Ferreira SH, Tambeli CH: Interferential therapy produces antinociception during application in various models of inflammatory pain. Phys Ther 86:800-808, 2006 29. Kahn J: Principles and Practice of Electrotherapy, 4th ed. New York, NY, Churchill Livingstone, 2000 30. Maeda Y, Lisi TL, Vance CG, Sluka KA: Release of GABA and activation of GABA(A) in the spinal cord mediates the effects of TENS in rats. Brain Res 1136:43-50, 2007 31. Manal TJ, Snyder-Mackler L: Electrical stimulation for pain modulation, in Robinson A, Snyder-Mackler L (eds): Clinical Electrophysiology: Electrotherapy and Electrophysiologic Testing, 3rd ed. Philadelphia, PA, Lippincott Williams and Wilkins, 2008, pp 151-196 32. McDowell BC: An investigation of the analgesic and neurophysiological effects of H-wave therapy. PhD Thesis, University of Ulster, 1995
34. Nussbaum EL, Downes L: Reliability of clinical pressurepain algometric measurements obtained on consecutive days. Phys Ther 78:160-169, 1998
36. Palmer S, Martin D: Interferential current, in Watson T (ed): Electrotherapy: Evidence-Based Practice, 12th ed. Philadelphia, PA, Churchill Livingstone, 2008, pp 297-315 37. Palmer ST, Martin DJ, Steedman WM, Ravey J: Alteration of interferential current and transcutaneous electrical nerve stimulation frequency: Effects on nerve excitation. Arch Phys Med Rehabil 80:1065-1071, 1999 38. Radhakrishnan R, Sluka KA: Deep tissue afferents, but not cutaneous afferents, mediate transcutaneous electrical nerve stimulation-induced antihyperalgesia. J Pain 6: 673-680, 2005 39. Rakel B, Cooper N, Adams HJ, Messer BR, Frey Law LA, Dannen DR, Miller CA, Polehna AC, Ruggle RC, Vance CG, Walsh DM, Sluka KA: A new transient sham TENS device allows for investigator blinding while delivering a true placebo treatment. J Pain 11:230-238, 2010 40. Robertson VJ, Ward AR, Low J, Reed A: Electrotherapy Explained: Principles and Practice, 4th ed. Oxford, UK, Butterworth-Heinemann, 2006 41. Scales DC, Adhikari NK: Maintaining allocation concealment: Following your SNOSE. J Crit Care 20:191-193, 2005 42. Shanahan C, Ward AR, Robertson VJ: Comparison of the analgesic efficacy of interferential therapy and transcutaneous electrical nerve stimulation. Physiotherapy 92:247-253, 2006 43. Shapiro S: Electrical currents, in Cameron MH (ed): Physical Agents in Rehabilitation: From Research to Practice, 3rd ed. St. Louis, MO, Saunders, 2008, pp 207-244 44. Sluka KA, Deacon M, Stibal A, Strissel S, Terpstra A: Spinal blockade of opioid receptors prevents the analgesia produced by TENS in arthritic rats. J Pharmacol Exp Ther 289:840-846, 1999 45. Sluka KA, Lisi TL, Westlund KN: Increased release of serotonin in the spinal cord during low, but not high, frequency transcutaneous electric nerve stimulation in rats with joint inflammation. Arch Phys Med Rehabil 87:1137-1140, 2006 46. Sluka KA, Vance CG, Lisi TL: High-frequency, but not low-frequency, transcutaneous electrical nerve stimulation reduces aspartate and glutamate release in the spinal cord dorsal horn. J Neurochem 95:1794-1801, 2005 47. Snyder-Mackler L: Electrical stimulation for pain modulation, in Robinson AJ, Snyder-Mackler L (eds): Clinical Electrophysiology: Electrotherapy and Electrophysiologic Testing, 2nd ed. Baltimore, MD, Williams and Wilkins, 1995, pp 279-310 48. Spielholz NI, Nolan MF: Conventional TENS and the phenomena of accommodation, adaptation, habituation, and electrode polarization. J Clin Electrophysiol 7:16-19, 1995 49. Starkey S: Therapeutic Modalities, 2nd ed. Philadelphia, PA, F.A., Davis Company, 1999
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50. Walsh DM, Foster NE, Baxter GD, Allen JM: Transcutaneous electrical nerve stimulation. Relevance of stimulation parameters to neurophysiological and hypoalgesic effects. Am J Phys Med Rehabil 74:199-206, 1995
52. Wang B, Tang J, White PF, Naruse R, Sloninsky A, Kariger R, Gold J, Wender RH: Effect of the intensity of transcutaneous acupoint electrical stimulation on the postoperative analgesic requirement. Anesth Analg 85:406-413, 1997
51. Walter SD, Eliasziw M, Donner A: Sample size and optimal designs for reliability studies. Stat Med 17:101-110, 1998
53. Ward AR: Electrical stimulation using kilohertzfrequency alternating current. Phys Ther 89:181-190, 2009
Adjusting Pulse Amplitude During Transcutaneous Electrical Nerve Stimulation (TENS) Application Produces Greater Hypoalgesia Manuela A. Pantale~ ao,* Marjorie F. Laurino,* Natalie L. G. Gallego,* Cristina M. N. Cabral,* Barbara Rakel,y Carol Vance,z Kathleen A. Sluka,z Deirdre M. Walsh,x and Richard E. Liebano* * University of the City of Sao Paulo (UNICID), Physical Therapy Department, Sao Paulo, Brazil. y College of Nursing, Graduate Program in Physical Therapy & Rehabilitation Science, University of Iowa, Iowa City, Iowa. z College of Medicine, Graduate Program in Physical Therapy & Rehabilitation Science, University of Iowa, Iowa City, Iowa. x University of Ulster, Health and Rehabilitation Sciences Research Institute, Newtownabbey, Northern Ireland, UK.
Abstract: Transcutaneous electrical nerve stimulation (TENS) is a noninvasive technique used for pain modulation. During application of TENS there is a fading of current sensation. Textbooks of electrophysical agents recommend that pulse amplitude should be constantly adjusted. This seems to be accepted clinically despite the fact that there is no direct experimental evidence. The aim of the current study was to investigate the hypoalgesic effect of adjusting TENS pulse amplitude on pressure pain thresholds (PPTs) in healthy humans. Fifty-six healthy TENS na€ıve participants were recruited and randomly assigned to 1 of 4 groups (n = 14 per group): control, placebo TENS, fixed pulse amplitude TENS, and adjusted pulse amplitude TENS. Both active and placebo TENS were applied to the dominant forearm. PPTs were recorded from 2 points on the dominant forearm and hand before, during, and after 40 minutes of TENS. TENS increased the PPTs on the forearm (P = .003) and hand (P = .003) in the group that received the adjusted pulse amplitude when compared to all other groups. The mean final pulse amplitude for the adjusted pulse amplitude TENS group was 35.51 mA when compared to the fixed pulse amplitude TENS group, which averaged 31.37 mA (P = .0318). Perspective: These results suggest that it is important to adjust the pulse amplitude during TENS application to get the maximal analgesic effect. We propose that the fading of current sensation allows the use of higher pulse amplitudes, which would activate a greater number of and deeper tissue afferents to produce greater analgesia. ª 2011 by the American Pain Society Key words: Transcutaneous electrical nerve stimulation, pain measurement, pain threshold.
T
ranscutaneous electrical nerve stimulation (TENS) is a nonpharmacologic and noninvasive treatment commonly used by health care practitioners as an adjunct treatment for a variety of painful conditions.4,12,35 The most popular theory for the mechanism of action of TENS is the gate control theory of pain.33,44 This theory proposes that stimulation of large-diameter Received June 23, 2010; Revised October 20, 2010; Accepted November 9, 2010. Supported by the Special Olympics World Board. TENS units were donated by Empi, Inc (USA). Address reprint requests to Richard Liebano, PT, PhD, Full Professor, University of the City of Sao Paulo (UNICID), Physical Therapy Department, Rua Cesario Galeno 448/475, Tatuape, Sao Paulo, SP - CEP 03071-000. E-mail: [email protected] 1526-5900/$36.00 ª 2011 by the American Pain Society doi:10.1016/j.jpain.2010.11.001
afferent fibers (Ab) activates local inhibitory circuits in the dorsal horn of the spinal cord and prevents nociceptive impulses carried by small-diameter fibers (C and Ad) from reaching higher brain centers.44,46 Despite the clinical popularity of more than 30 years of use of TENS for the treatment of pain and an extensive research base, there is little consensus regarding the optimal parameters required to induce maximal hypoalgesic effects.8,50 During application of TENS there is a fading of current sensation.13 This phenomenon is usually attributed to adaptation, habituation, or accommodation to electrical stimulation. Adaptation is defined as a decrease in the frequency of action potentials, and a decrease in the subjective sensation of stimulation when electrical stimulation is applied when there is no change in the applied stimulus.43 Habituation occurs when electrical 581
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stimulation continues to evoke action potentials but there is a reduction in the central nervous system response.40 The term accommodation is used to refer to a rise in membrane threshold potential associated with a slowly applied depolarization current.48 For this reason, most TENS devices provide the option of modulation of current parameters to avoid these effects. In textbooks of electrophysical agents, it is recommended that stimulus intensity (pulse duration or pulse amplitude) should be constantly adjusted during treatment to prevent adaptation, accommodation, and habituation.3,5,31,47,49 This seems to be accepted despite the fact that there is no direct experimental evidence. Defrin et al13 demonstrated that the fading of sensation during interferential current (IFC) treatment does not decrease the analgesic effect when treating patients with chronic pain due to knee osteoarthritis. The physical properties of IFC and TENS are quite different.42 The active element of TENS is biphasic low-frequency pulsed currents (1–200 Hz) whereas IFC is a type of medium-frequency alternating current, with carrier frequencies of 1 to 10 kHz and modulated in amplitude.25,42 Theoretically, IFC has the advantage of reducing the skin impedance normally incurred by traditional low-frequency currents and deeper penetration into tissues.7,25,37 To our knowledge, no previous experimental pain studies have systematically assessed the influence of fading of sensation on hypoalgesic effects during TENS applications. With these concerns in mind, the aim of the present investigation was to investigate the hypoalgesic effect of adjusting TENS pulse amplitude using upper limb pressure pain threshold (PPT) in healthy volunteers. A randomized placebo-controlled blinded design was used.
Methods Participants After obtaining approval from the University of the ~o Paulo’s Research Ethics Committee, 56 TENS City of Sa na€ıve healthy volunteers were recruited from the staff and students of the University (28 males, 28 females; mean age, 22 years; range 18–36 years). Participants were screened (Investigator 1) for relevant contraindications including injury or nerve damage to the upper limbs, current pain, pregnancy, chronic illness, cardiac pacemaker, epilepsy, allergies to the TENS electrodes, currently taking pain medication, skin conditions or deficient skin sensation in the areas of electrode placement. After giving informed written consent, participants were stratified by gender11,39 to ensure equal numbers of men and women in each group and randomly allocated to 1 of 4 groups (n = 14 per group): Fixed Pulse Amplitude TENS; Adjusted Pulse Amplitude TENS; Placebo TENS; and Control (Fig 1). Randomization was performed by an investigator not involved in data collection using the sequentially numbered, opaque sealed envelopes (SNOSE) allocation concealment method.15,41 The envelopes were stored in a secure cabinet that only the allocation investigator had access to and were opened immediately prior to intervention allocation.
Pulse Amplitude During TENS Application Sample size was calculated using a mean difference of 10.1 N (active TENS versus placebo TENS) and standard deviation of 6.98 N obtained from previous data on PPT and TENS.32 At a significance level of .05 and power of 80%, it was calculated that 12 participants were required in each group (Minitab, v.15; Minitab, State College, PA). Allowing for attrition, 14 participants were recruited per group.
Participant Preparation The participants were asked to remain seated in a comfortable upright position during all procedures. Participants’ upper limbs were cleaned prior to marking electrode placement and PPT recording sites using a marker. The electrode placement sites were marked out as described below. Two PPT recording sites were marked out the dominant upper limb as follows: 1) 3 cm distal to the distal end of the anatomical snuff box in the midline of the belly of the first dorsal interosseous muscle (Fig 2A); and 2) on the anterior aspect of the forearm, 7.5 cm proximal to the distal wrist crease (Fig 2B). These sites were chosen to examine the effects of TENS within (hand and forearm) the area of stimulation.
Pressure Pain Threshold Measurements PPT was recorded by Investigator 2 who was blind to group allocation using a Kratos pressure algometer (DDK, Kratos Equipments, Brazil) (Fig 2A and B). The algometer was calibrated prior to the beginning of the study. A preliminary reliability study was conducted by Investigator 2 by recording PPT from the 2 recording points described above from 10 healthy volunteers on 2 occasions, 48 hours apart.11,51 This reliability study demonstrated excellent overall between-session intrarater reliability for PPT measurements from the hand (.92) and from the forearm (.98). In the current study, Investigator 2 was kept blind to the group allocation. In addition, electrodes were applied to all participants’ forearms and the display of the TENS unit was covered during PPT measurements to conceal if active or placebo TENS was being applied. Participants’ hands and forearms were covered with a cardboard box containing 2 holes over the PPT recording points. This prevented Investigator 2 from seeing any muscle contractions during PPT measurements. During PPT recording, the circular probe of the algometer (1 cm2 area) was placed perpendicular to the skin and applied at a constant rate (approximately 5 N/s). Participants were asked to say stop when the sensation they were feeling turned to pain (distinct from pressure or discomfort). A sign was placed on the wall above the participants’ eye levels and they were asked to look at this sign during PPT recordings (text on sign = ‘‘Say STOP when you feel a sensation of pain distinct from pressure or discomfort’’). Three measurements (in N) were taken from each recording site at each time point and the average used for data analyses.10,16-19,34 The pressure in kPa was calculated using the following formula: P [Pa] = F [N]/A [m2], where P is the pressure, F is the applied force, and A is the area of the
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Figure 1. Study design and flow of participants through the study.
algometer probe. The TENS intervention was not interrupted to take PPT recordings. At the 2 recording sites, PPT was recorded at 0, 20, 40, and 60 minutes. During the study, PPT readings from the 2 recording sites were taken in a random order to avoid order bias.11,19 Randomization was performed using a computer-generated random number list compiled by an investigator not involved in data collection. This random order was concealed by writing the order onto cards and sealing them in the same opaque envelopes used for group allocation. These cards were given to Investigator 2 only after informed consent was obtained from each participant. All participants were given 2 practice demonstrations of PPT on their nondominant forearm to en-
sure they understood the concept of PPT recording before the study began.
Groups The interventions were applied to the dominant upper limb by Investigator 1 as described below.
Fixed Pulse Amplitude TENS Two 50 90 mm standard self-adhesive electrodes (ValuTrode; Axelgaard, Fallbrook, CA) were positioned on the lateral aspect of the forearm at the level of the distal wrist crease and the lateral aspect of the forearm, 10 cm proximal to the distal wrist crease (Fig 2A and B). Once TENS was applied, the pulse amplitude was gradually
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Figure 2. (A) Electrode position and location of the PPT recording point on the hand. (B) Electrode position and location of the PPT recording point on the forearm.
increased until a strong but comfortable subjective intensity was reported by the participant. The pulse amplitude was maintained at this level (ie, not adjusted at all) for the duration of the 40-minute treatment.
Adjusted Pulse Amplitude TENS Electrodes applied as above. The pulse amplitude was gradually increased until a strong but comfortable subjective intensity was reported by the participant. At 5-minute intervals, the participants were asked if the sensation had faded and the pulse amplitude was increased again to a subjective strong but comfortable intensity level.
Placebo TENS Electrodes applied as above. The sham device was a Select TENS unit (Empi, St. Paul, MN) modified to deliver a stimulus for a total of 42 seconds at a strong but comfortable intensity level (burst stimulus with 100-Hz frequency and a 5-second cycle time) after which time the current amplitude resets to 0 mA.39 Participants in this group were asked every 5 minutes if they were comfortable.
Control Electrodes applied as above and leads connected to the TENS unit but no TENS applied. The TENS units were calibrated using an oscilloscope prior to the study commencing. In the 2 active TENS groups, TENS was applied using a continuous output at 100 Hz for 40 minutes (Select TENS unit, Empi) while the participant was seated with the dominant forearm placed on a wooden table. Participants in the 2 active and placebo groups were given a demonstration of their allocated intervention on the nondominant forearm be-
fore the baseline (0 minute) PPT reading was taken. The pulse amplitude was increased to sensory threshold for this demonstration. The pulse duration of the Select TENS unit varied with the amplitude applied (range 0 to 400 ms at 50% peak amplitude). Participants in the Placebo TENS and both active TENS groups were blind to group allocation; they were told that they may or may not feel a tingling sensation. In the Control group, participants were told that they would not receive an intervention.
Pulse Amplitude The value of the pulse amplitude was calibrated for each participant. This was done by measuring the peakto-peak voltage of the waveform across a 1 kU resistor on an oscilloscope. The pulse amplitude required to produce a strong but comfortable sensation was recorded every 5 minutes for the Adjusted Pulse Amplitude TENS group.
Assessing Blinding At the end of data collection, the effectiveness of blinding was assessed by Investigator 1 asking both the participant and Investigator 2 which TENS intervention they thought was delivered with 3 options for the answer: ‘‘real,’’ ‘‘placebo,’’ or ‘‘don’t know.’’ Their responses to this question were recorded and used to gauge the adequacy of subject and investigator blinding.39
Data Analysis Data were analyzed using SPSS software (v.17; SPSS Inc; Chicago, IL) by an investigator who was blind to group allocation: an average of the 3 PPT scores recorded at each time point was used for analysis. Shapiro-Wilk tests showed that the data were normally distributed,
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Table 1. Mean 6 SEM Raw PPT Scores for All Time Points, for Each Group (n = 14 Per Group) for Hand PPT Measurements TENS APPLICATION GROUP
BASELINE
20 MIN
40 MIN
POST TENS 60 MIN
Control Placebo TENS Fixed Pulse Amplitude TENS Adjusted Pulse Amplitude TENS
244.04 6 24.25 260.49 6 28.66 220.33 6 28.81 241.57 6 24.78
237.42 6 19.07 281.59 6 30.86 250.80 6 34.83 296.21 6 28.73
237.49 6 18.09 263.06 6 23.59 241.30 6 32.43 356.34 6 37.81
229.11 6 17.53 263.52 6 26.18 217.88 6 34.16 258.89 6 23.99
NOTE. All values are expressed in kPa.
therefore parametric tests were used to analyze the data. Percentage of change (variation from baseline values) was analyzed using between-within groups ANOVA and post hoc Tukey tests. c2 test was used to compare blinding of the groups against an expected result of 50:50 blinding (ie, chance). The unpaired t test compared the final pulse amplitude applied in the Fixed Pulse Amplitude TENS group and in the Adjusted Pulse Amplitude TENS group. One-way ANOVA compared the pulse amplitudes over time in the Adjusted Pulse Amplitude TENS group. Significance was set at P < .05.
Results PPT Data Data for the raw mean (6SEM) PPT scores for all experimental groups are summarized in Tables 1 (hand measurement site) and 2 (forearm measurement site). The percentage of PPT change in the hand over the 60 minutes is summarized in Fig 3. The greatest increase in PPT was observed in the Adjusted Pulse Amplitude TENS group, representing a greater hypoalgesic effect in this group. Fig 4 shows the percentage of PPT change in the forearm over the 60 minutes. Again, the greatest increase in PPT was observed in the Adjusted Pulse Amplitude TENS group. Statistical analyses of the PPT data at the hand using between-within groups ANOVA showed significant differences: over time (P < .0001); interactive effect between time and group (P < .0001); and between groups (P = .003). Post hoc Tukey tests indicated a significant hypoalgesic effect in the Adjusted Pulse Amplitude TENS group compared with all the other groups; there was
no significant difference between any of the other groups (Control, Placebo TENS, and Fixed Pulse Amplitude) (P > .05). Post hoc tests for statistical comparison between groups at the hand are summarized in Table 3. On the forearm, analysis of PPT data showed neither significant difference over time (P = .414) nor an interactive effect between time and group (P = .601). However, there was a significant difference between groups (P = .003). Similar to the observed changes in PPT data at the hand, the Adjusted Pulse Amplitude TENS group showed a greater hypoalgesic effect when compared to the other groups. There was no significant difference between any of the other groups (Control, Placebo TENS, and Fixed Pulse Amplitude TENS) (P > .05). Post hoc tests for statistical comparison between groups at forearm are summarized in Table 4.
Pulse Amplitude Data The mean pulse amplitude used in all groups is shown in Table 5. The data showed an increase in pulse amplitude over time in the Adjusted Pulse Amplitude TENS group (P < .0001) and a significant difference between the pulse amplitude used in the Fixed Pulse Amplitude TENS and the Adjusted Pulse Amplitude TENS group at 40 minutes (unpaired t test, P = .0318).
Assessment of Blinding The pain assessor correctly identified that participants received active TENS in 35.7% (5/14) of cases in the Fixed Pulse Amplitude TENS group and in 28.6% (4/14) of the Adjusted Pulse Amplitude TENS group. In the placebo TENS group, the assessor correctly identified that participants received placebo TENS in 21.4% (3/14) of cases.
Table 2. Mean 6 SEM Raw PPT Scores for All Time Points, for Each Group (n = 14 Per Group) for Forearm PPT Measurements TENS APPLICATION GROUP
BASELINE
20 MIN
40 MIN
POST TENS 60 MIN
Control Placebo TENS Fixed Pulse Amplitude TENS Adjusted Pulse Amplitude TENS
263.79 6 21.19 308.65 6 39.22 255.66 6 37.05 269.97 6 28.60
278.77 6 22.92 292.75 6 29.98 266.80 6 39.54 354.95 6 38.43
280.68 6 25.00 293.63 6 31.17 262.69 6 38.44 338.26 6 29.55
274.78 6 25.98 304.27 6 35.75 251.45 6 36.63 317.57 6 37.68
NOTE. All values are expressed in kPa.
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Figure 3. Percentage of change in pressure pain threshold (PPT) in the hand for each experimental group (mean 6 SEM). In the Fixed Pulse Amplitude TENS group, 8 of 14 participants correctly identified that they received real TENS, 5 thought they received placebo TENS, and 1 did not know. In the Adjusted Pulse Amplitude TENS group, 10 of 14 participants correctly identified that they received real TENS, 2 thought they received placebo TENS, and 2 indicated that they did not know. However, in the placebo TENS group, only 3 of 14 participants correctly identified that they received placebo TENS, 8 thought they received real TENS, and 3 indicated that they did not know. The rate of blinding in the placebo TENS group was different than chance (random 50:50 probability) (c test, P = .0325), indicating successful participant blinding in this group.
Discussion During the application of TENS, it is frequently reported that the sensation of tingling or buzzing beneath the electrodes gradually decreases with time, even though the pulse charge remains the same.48 It is usually recommended that current amplitude or pulse duration should be constantly adjusted when the sensation decreases.3,5,13,47,49 This recommendation led the manufacturers to incorporate stimulation parameter modulation (such as frequency, pulse duration, and amplitude) in most TENS devices despite the fact that there is no experimental evidence to support this claim. The purpose of this study was to determine if the constant increase in pulse amplitude could improve the
hypoalgesic effect of TENS. The results presented herein confirm the importance of adjusting pulse amplitude during TENS application. PPTs recorded from both hand and forearm showed a significantly higher increase in the Adjusted Pulse Amplitude TENS group when compared with Fixed Pulse Amplitude TENS, Placebo TENS and Control groups. A possible explanation for this finding is that the decrease in sensation during TENS application allows the use of higher pulse amplitudes. Several studies have shown the importance of the use of high-intensity TENS stimulation for pain control in humans.1,4,8,9,35,39,52 An experimental study in rats demonstrated that large diameter primary afferent fibers from deep tissue are required for TENS-induced antihyperalgesia.38 Based on the results of the current study, we suggest that the use of higher pulse amplitudes activates a greater number of and deeper tissue afferents to produce greater hypoalgesic effect. In the Adjusted Pulse Amplitude TENS group, the final average pulse amplitude was 13.2% higher than the amplitude applied in the Fixed Pulse Amplitude TENS group. In the Select TENS unit used in the present study, the pulse duration increased (up to a maximum of 400 ms) as the pulse amplitude increased. Thus, it is reasonable to expect an even higher increase in pulse amplitude, during the 40-minute intervention, if the pulse duration was fixed. According to gate control theory of pain, the stimulation of large-diameter afferent fibers (Ab) by TENS activates local inhibitory circuits in the dorsal horn of the spinal cord and prevents nociceptive
Figure 4. Percentage of change in pressure pain threshold (PPT) in the forearm for each experimental group (mean 6 SEM).
Pantale~ao et al Table 3.
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Summary of Post Hoc Tukey Tests for Statistical Comparison Between Groups at the Hand GROUP
Control
Placebo TENS Fixed Pulse Amplitude TENS
COMPARISON GROUP
MEAN DIFFERENCE BETWEEN GROUPS
STANDARD ERROR
P VALUE
Placebo TENS Fixed Pulse Amplitude TENS Adjusted Pulse Amplitude TENS Fixed Pulse Amplitude TENS Adjusted Pulse Amplitude TENS Adjusted Pulse Amplitude TENS
5.54 6.01 27.85 .46 22.30 21.84
7.64 7.64 7.64 7.64 7.64 7.64
.886 .860 .003 1.000 .026 .030
NOTE. All values are expressed in percentage of PPT change. Bold numbers represent significant P value.
impulses carried by small-diameter fibers (C and Ad) from reaching higher brain centers.33,44,46 Considering the habituation concept, it is possible that in the Fixed Pulse Amplitude TENS group, an interruption of the activation of inhibitory circuits in the dorsal horn of the spinal cord impaired the hypoalgesic response. On the other hand, the constant increase of pulse amplitude (in the Adjusted Pulse Amplitude TENS group) could have activated a large number of large-diameter afferent fibers, keeping the activation of inhibitory interneurons in the dorsal horn for a greater period of time. Contrary to our results, a previous study using IFC in patients with chronic knee osteoarthritis showed that the fading of current sensation during treatment did not impede its analgesic effect.13 It is noteworthy that IFC is a medium-frequency alternating current, with amplitude modulated at low frequency,36 whereas TENS units deliver low-frequency pulsed currents. Moreover, these authors used an amplitude-modulated frequency (AMF) constantly ranging between 30 and 60 Hz, and assessed pain intensity using a visual analog scale (VAS), morning stiffness, range of motion, electrical pain threshold, and percentage of pain reduction. In the current study, the pulse frequency was kept constant and pressure pain thresholds were used as the outcome measure. Thus, differences in experimental design may account for these findings. As skin impedance is inversely proportional to the frequency of alternating current (AC), it has been claimed that IFC has the advantage of diminishing the impedance of the skin and subcutaneous tissues and can therefore penetrate into the deeper tissues when compared with low-frequency pulsed currents delivered by TENS devices. Although this theory has been widely reported in
the literature,6,7,20,23-28,37 to our knowledge there are no experimental studies that confirm this theory. Moreover, the theory has been questioned by some authors2,53 because skin impedance to pulsed current depends on the phase duration, not the pulse frequency. Thus, if the pulsed current has the same phase duration as the kilohertz-frequency AC, the skin impedance would be the same even if the pulse frequency is low.53 Future studies are therefore needed to clarify this proposed effect of IFC. The current study used a novel type of sham TENS unit to deliver placebo TENS that has been recently validated.39 This sham unit looked identical to the active TENS unit. It delivered a burst stimulus for 42 seconds and then the current output resets to 0 mA. The fact that the sham unit delivers electrical current for a short period of time increases the rate of participant blinding.11,39 The percentage of participants that correctly identified whether the intervention was real or placebo was 57% in the Fixed Pulse Amplitude TENS group, 71.4% in the Adjusted Pulse Amplitude TENS group, and 21.4% in the placebo TENS group. The fact that participants correctly identified the intervention more often in active groups was not surprising and it is consistent with prior research.11,14,39 Our data support this type of placebo TENS as a useful model in TENS research, as minimal hypoalgesic effects were observed and it produced a very high level of participant blinding. The decrease in sensation during TENS application has been attributed to accommodation,21,29,31,49 adaptation,13,43 and habituation.40,48 Spielholz and Nolan48 debated what was the proper term to describe the phenomenon of fading in sensation during conventional TENS. The authors propose that habituation best
Summary of Post Hoc Tukey Tests for Statistical Comparison Between Groups at the Forearm
Table 4.
GROUP Control
Placebo TENS Fixed Pulse Amplitude TENS
COMPARISON GROUP
MEAN DIFFERENCE BETWEEN GROUPS
STANDARD ERROR
P VALUE
Placebo TENS Fixed Pulse Amplitude TENS Adjusted Pulse Amplitude TENS Fixed Pulse Amplitude TENS Adjusted Pulse Amplitude TENS Adjusted Pulse Amplitude TENS
6.03 3.48 22.46 2.55 28.50 25.94
8.02 8.02 8.02 8.02 8.02 8.02
.875 .972 .035 .989 .004 .011
NOTE. All values are expressed in percentage of PPT change. Bold numbers represent significant P value.
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Table 5.
Mean 6 SEM Pulse Amplitude Applied in all Experimental Groups Over Time
GROUP
0 MIN
5 MIN
10 MIN
15 MIN
20 MIN
25 MIN
30 MIN
35 MIN
40 MIN
Control — — — — — — — — — Placebo TENS 29.05 6 1.91 — — — — — — — — Fixed Pulse 31.37 6 1.49 31.37 6 1.49 31.37 6 1.49 31.37 6 1.49 31.37 6 1.49 31.37 6 1.49 31.37 6 1.49 31.37 6 1.49 31.37 6 1.49 Amplitude TENS Adjusted Pulse 30.19 6 1.54 31.69 6 1.22 32.16 6 1.18 33.18 6 1.06 33.79 6 0.99 34.46 6 0.98 35.07 6 0.97 35.29 6 1.03 35.51 6 1.09 Amplitude TENS NOTES. All values are expressed in mA. The unpaired t test revealed a significant difference between mean pulse amplitude in the Fixed Pulse Amplitude TENS and Adjusted Pulse Amplitude TENS at 40 min (P = .0318). Over the 40 min of TENS application in the Adjusted Pulse Amplitude TENS group, there was a significant increase in pulse amplitude (1-way ANOVA, P < .0001); the final mean pulse amplitude was 19.99 6 4.16% higher than the mean pulse amplitude used at the beginning of the experiment.
describes this physiological response that results in a decrease in neurotransmitter release from afferent nerve terminals due to the inactivation of Ca11 channels in the presynaptic membrane. As a result, local interneurons and ascending projection neurons are no longer depolarized, although action potentials continue to be transmitted toward the central nervous system from primary afferent fibers.22,48 However, work from Sluka et al show continued release of neurotransmitters in the spinal cord throughout a 20-minute TENS
treatment.30,45,46 Thus, increasing amplitude to avoid habituation over the course of treatment could activate a greater number afferent fibers to enhanced neurotransmitter release in the central nervous system. In summary, the data presented here have confirmed that increasing pulse amplitude during TENS application has an important role in its hypoalgesic effect, using an experimental model of pain. Future clinical studies should be performed to confirm these results in patients experiencing pain.
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