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Preliminary Communication

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Transcutaneous electrical nerve stimulation is


superior than placebo and control for
postoperative pain relief
Maraı́sa Rodrigues Borges1 , Nuno Miguel Lopes de Oliveira2 , Izabella Barberato Silva
Antonelli1 , Maristella Borges Silva3 , Eduardo Crema2 & Luciane Fernanda Rodrigues
Martinho Fernandes*,2
1
Department of Applied Physiotherapy, Federal University of Triangulo Mineiro, Uberaba, MG, Brazil
2
Medical School, Federal University of Triangulo Mineiro, Uberaba, MG, Brazil
3
The study was performed at Clinics Hospital of the Federal University of Triangulo Mineiro, Uberaba, MG, Brazil
*Author for correspondence: Tel.: +55 34 33136175; luciane.fernandes@uftm.edu.br

Practice points
• Transcutaneous electrical nerve stimulation (TENS) is a physical modality, nonpharmacological intervention
strategy.
• TENS is noninvasive, inexpensive, safe and easy to use.
• A decrease of 2 points on the visual analog scale for 53.8% of patients following active TENS was reported.
• TENS was more effective for pain relief in patients submitted to laparoscopic cholecystectomy.
• TENS reduced pain intensity.
• TENS had no reported side effects.
• Inadequate acute pain management may result in a significant increase in healthcare costs.
• Lack of postoperative pain management may decrease patient satisfaction.

Aim: To determine whether transcutaneous electrical nerve stimulation (TENS) is more efficient than
placebo TENS and control groups for pain relief. Design: Randomized, single-blinded, placebo-controlled
trial. Setting & participants: A total of 78 adults with postoperative pain, after cholecystectomy, at
the University Hospital. They were randomized into active TENS, placebo TENS and control. Interven-
tion: A total of 30-min interventions applied in the first 24 h after the surgery. Outcome: Pain inten-
sity. Results: Pain significantly decreased for both TENS; however, the active TENS was better. A de-
crease of 2 points or more on the visual analog scale for 53.8% active TENS and 11.5% placebo. Con-
clusion: There was a greater reduction in pain of important clinical relevance in the active TENS group.
Clinical Trial registration: Brazilian Clinical Trial (REBEC): RBR-6cgx2k.

First draft submitted: 7 January 2020; Accepted for publication: 3 March 2020; Published online:
22 June 2020

Keywords: acute pain • analgesia • cholecystectomy • postoperative • transcutaneous electrical stimulation • treat-
ment outcome

Pain is the most frequent symptom, both before and after laparoscopic cholecystectomy (LC) [1] and one of the most
common reasons for staying overnight in hospitals [2]. Besides pain, there are other complaints that may be related
to hospitalization, such as nausea and patient’s fear of being discharged [2]. Pain may be described as incisional pain,
abdominal pain or shoulder pain (referred from the subdiaphragmatic region) [3,4]. Following surgery on the day,
it is usually more intense, declining to lower levels over the first 2–4 days, but there is substantial interindividual
variability [1,5]. Postoperative pain depends on multiple factors, such as distension of the peritoneal cavity [6],
intra-abdominal gas [7] or bile leak [8].
The primary reason for prolonged hospitalization and consequential increase in morbidity after cholecystectomy
is postoperative pain. Improved pain relief and patient information may further reduce convalescence [9]. For
pain reduction after LC, the recommendation of Guidelines on the Management of Postoperative Pain is to offer
multimodal analgesia or a combination of different analgesic drugs and nonpharmacological interventions, that

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Preliminary Communication Borges, de Oliveira, Antonelli, Silva, Crema & Fernandes

may include administration of opioids, acetaminophen and/or non-steroidal anti-inflammatory drugs, ketamine,
cognitive modalities and transcutaneous electrical nerve stimulation (TENS) [10]. Nausea, vomiting and patient’s
satisfaction are some of the side effects of high doses of analgesic drugs [11]. It is important to highlight that patients
with tolerance abuse or addiction should be carefully treated with opioids since it may be a trigger to precipitation of
relapse or worsening addiction [10]. According to the biopsychosocial model of pain, the use of nonpharmacological
interventions may result in additional effects [10].
The nonpharmacologic techniques such as TENS or transcutaneous acupoint electrical stimulation, have been
used after LC for evaluating pain relief and reducing analgesic drug effects [12–16]. TENS is a physical, nonpharma-
cological modality used for pain management and can be defined as a procedure of controlled low-voltage electrical
stimulation application to the nervous system for reduction of pain symptoms. The electricity is passed through
the skin by electrodes placed on the skin [17]. It is very safe, portable, noninvasive, compact, inexpensive and easy
to operate [17].
Although there are trials suggesting that TENS has beneficial effects for acute pain reduction, many of these
trials published have small sample sizes and/or inadequate blinding leading to a high risk of bias, which can
be difficult for drawing conclusions, based on the evidence, that TENS is more efficient in reducing pain over
placebo TENS [18]. Thus, it is not possible to make a meaningful judgment based on clinical efficacy of TENS [19].
Another issue, equally important, is inadequate technique, for example short therapy duration and low stimulation
intensity. According to Chesterton et al., low intensity TENS compromises TENS effectiveness [20]. The intensity
should be related to patient’s individual response and it is usually increased to the maximal level tolerated by the
patient, before discomfort [21]. Considering therapy application time, the duration of stimulus is, at least, between
30 and 60 min [17]. One way of assisting clinicians in the choice of appropriate dosing/parameters for the most
effective TENS, is to have more studies investigating electrode site selection, daily treatment duration and long-term
usage [22].
As a result of an interdisciplinary expert panel in which guidelines on postoperative pain management were
established, TENS is recommended as an adjunct resource [10]. This recommendation is considered weak and the
evidence is of moderate quality [10], although TENS is reported to promote satisfying pain relief by those patients
who have used the resource [23] and there is positive evidence from systematic reviews of placebo-controlled trials
suggesting pain relief by TENS [24,25] and reduction of analgesic consumption [26]. We performed this study aiming
to determine wether TENS was more effective than placebo TENS for controlling pain relief in patients who had
undergone LC.

Materials & methods


Trial design
A prospective, single-blind randomized placebo-controlled trial was performed aiming to compare the pain relief
effect of TENS versus placebo TENS versus control in postoperative LC patients.

Participants & recruitment


Participants were patients that underwent LC and were assisted immediately postoperative or on the first day
following surgery. All subjects freely signed an informed consent form in accordance with regulation 466/12 of
the National Health Council and Helsinki Declaration, after being informed of procedures and objectives of the
study. The local ethics committee approved the research (protocol number 1135/2008) and it was then updated
(protocol number 2.448.177) and registered as a Clinical Trial (ClinicalTrials.gov: UTN U1111-1207-7652).
To be eligible, patients had to be aged over 18 years and submitted to elective LC at the University Hospital
with postoperative pain scores above 0 using the visual analog scale (VAS). The exclusion criteria included,
intraoperative complications, mental and/or neurological disease and any cognitive deficit which could compromise
the understanding of the pain scale [16].
Out of 167 LC patients, 78 participants were included in the study. A total of 89 were excluded because they
either presented with no pain at evaluation or were under 18 years of age. The number of patients who had no
pain complaints was used to calculate the prevalence. The pain prevalence after LC was 47%. Recommendations
of Consolidated Standards of Reporting Trials were followed in this study [27]. Figure 1 presents the clinical trial
steps diagram.

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TENS in postoperative pain relief Preliminary Communication

Assessed for eligibility (n = 167)

Excluded (n = 89)
Not meeting inclusion criteria (n = 89)
– Under 18 years old (n = 4)
– No pain (n = 85)

Randomized (n = 78)

Active TENS group: Placebo TENS group: Control group:


Allocated to intervention (n = 26) Allocated to intervention (n = 26) Allocated to intervention (n = 26)
Received allocated intervention Received allocated intervention Received allocated intervention
(n = 26) (n = 26) (n = 26)
Did not receive allocated intervention Did not receive allocated intervention Did not receive allocated intervention
(n = 0) (n = 0) (n = 0)

Active TENS group: Placebo TENS group: Control group:


Lost to follow-up (n = 0) Lost to follow-up (n = 0) Lost to follow-up (n = 0)
Discontinued intervention (n = 0) Discontinued intervention (n = 0) Discontinued intervention (n = 0)

Active TENS group: Placebo TENS group: Control group:


Analysed (n = 26) Analysed (n = 26) Analysed (n = 26)
Excluded from analysis (n = 0) Excluded from analysis (n = 0) Excluded from analysis (n = 0)

Figure 1. Clinical trial steps diagram.


TENS: Transcutaneous electrical nerve stimulation.

Randomization
One investigator who was not directly involved with the assessment and treatment of patients performed a simple
randomization. Envelopes, opaque and sealed, consecutively numbered, were used in the allocation [27–29]. Data
were collected for initial assessment during either the immediate postoperative period or on the first postoperative
day [16]. The data included personal information, period of hospitalization, history of surgery and anesthesia,
number of postoperative days and pain site and intensity [16]. This information was collected either through the
patients’ medical records or from the patients themselves [16].
In order to calculate the sample size, a pilot study was carried out with 18 patients (9 in active TENS group and 9
in placebo TENS). The chosen variable for the sample size calculation was the difference between VAS values at the
two application moments (M2-M1) for both groups. The mean and standard deviation (SD) values of difference

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Preliminary Communication Borges, de Oliveira, Antonelli, Silva, Crema & Fernandes

(M2-M1) for active TENS group were 2.77 (±0.88) and for Placebo TENS were 2.58 (±1.01). Afterward, we
calculated the differences of mean and SD values between the groups. These values were 0.19 for mean and 0.13
for SD. The minimum considerable detectable difference between the groups was 0.5. According to this, a sample
size of at least 16 patients per group is a requirement for α = 0.05 and 90% power.

Blinding
This was a single blinded trial (patient). The patients were instructed that they might not feel the TENS current
due to accommodation sensation. The intensity current was increased during the treatment. In order to have the
blinding done in the placebo group, the examiner instructed patients on TENS treatment that they would feel the
analgesic effect but no current sensation. The same technique of electrode placement was used in both groups:
placebo TENS and active TENS. The only difference was that, in the placebo group, the unit emitted the active
indicator light, but no electrical stimulation was being delivered [30,31].

Anesthetic procedures
Anesthesia followed the standard adopted by the Anesthesia Service at this University Hospital for all cholecys-
tectomy surgeries. The pattern adopted is described as: preanesthetic medication administered 3 h before surgery,
which consisted of oral diazepam (10 mg), intravenous midazolam (5 mg) and volume expansion with 1000 ml
saline; induction of anesthesia: alfentanil (30 mg/kg), etomidate (0.3 mg/kg) and atracurium (0.5 mg/kg); main-
tenance of anesthesia: continuous infusion of alfentanil (1 mg/kg/min) and isoflurane (0.5–1.5%); decurarization:
intravenous atropine (1 mg) and prostigmin (2 mg) [32].

Surgical procedures
General anesthesia was administered to patients who were in dorsal decubitus on the operating table. During
surgery, patients were monitored on cardioscopy, pulse oximetry, capnography and noninvasive blood pressure.
Pneumoperitoneum was maintained by using a pressure of 12 mmHg [32].
LC is a surgical technique in which the gallbladder is removed. For these surgeries, four cannulas were inserted.
A 10-mm tube with a camera was inserted in the supraumbilical incision and a 5-mm tube in the right flank
for cranial traction of the gallbladder. The other 5-mm cannula was inserted in the right upper quadrant for the
gallbladder removal and another 10-mm canula in the epigastrium incision, left-sided round ligament, so that
dissection and hemostasis could be performed [32].
Through lateral retraction, the hilum was exposed and the infundibulum was righted and retracted downward.
The surgeon isolated, ligated and sectioned the cystic duct. After identifying the cystic artery, it was isolated and
metal clipped. Then the gallbladder was removed from the liver bed [32].
All surgeries were performed by the same surgical team and the chief surgeon is one of the study researchers.

Intervention postoperative procedures


Patients from the three groups received the same postoperative drug protocol: every 8 h after surgery, 2 ml of venous
dipyrone and 100 mg of subcutaneous tramadol were administered. Number of postoperative days varied from 1
to 6 (1.23 ± 0.83).
For patients with pain and/or discomfort at incision sites after surgery, interventions of active and placebo TENS
were applied only once during the first 24 h [16]. The instrument used for pain measurement was the VAS. It is a
10 cm two-sided ruler. The ruler face that is shown to the patient has the words ‘no pain’ and ‘the worst possible
pain’ on the left and on the right is faces depicting the pain. On the side of the ruler which the examiner can see, is
a numerical scale ranging from 0 (‘no pain’) to 10 (‘the worst possible pain’), with 1-mm divisions [33].
The researchers used the two-channel portable equipment TENS and functional electrical stimulation (Neurodyn
by Ibramed, São Paulo, Brazil). The equipment had been calibrated by the manufacturer [16]. Under the protocol
number 10360310012, the Brazilian National Health Surveillance Agency registered this equipment. In order to
achieve effective and fast pain relief, it was used with the conventional TENS current (frequency of 150 Hz and a
pulse width of 75 μs) [16].
The patients were told to report the maximum tolerable intensity [34] in which they would not feel pain,
discomfort or muscle contraction so that accommodation was avoided [16,35,36]. The researchers used silicone and
carbon rubber electrodes attached with gel, fixed onto the pain site using adhesive tape.

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Table 1. General and clinical characterization baseline data (n = 78).


Variables Control (n = 26) Active TENS (n = 26) Placebo TENS (n = 26)
Female, n (%) 23 (88.5%) 22 (84.6%) 23 (88.5%)
Age (years) 42 (±16) 50 (±15) 46 (±16)
Disease:
– Cholelithiasis 23 (88.5%) 23 (88.5%) 25 (96.2%)
– Choledocolithiasis 0 (0%) 1 (3.8%) 1 (3.8%)
– Gallbladder polyps 2 (7.7%) 0 (0%) 0 (0%)
– More than one diagnosis 1 (3.8%) 2 (7.7%) 0 (0%)
Pain sites:
– Umbilical incision 26 (100%) 24 (92.4%) 23 (88.5%)
– Subcostal incision 0 (0%) 1 (3.8%) 1 (3.8%)
– Epigastric incision 0 (0%) 1 (3.8%) 1 (3.8%)
– Abdomen 0 (0%) 0 (0%) 1 (3.8%)
Pre-TENS pain intensity 2.7 (±1.47) 3.1 (±1.63) 2.5 (±1.58)
TENS: Transcutaneous electrical nerve stimulation.

In order to cover the pain site, the four-pole technique (four rectangular 3 × 5 cm) was used. Avoiding the
probability of mechanical damage on the incision site at the moment of electrodes removal, they were placed at
5 cm from the site of the suture line [19].
For the placebo TENS group, the same electrode placement protocol was used. In the placebo TENS group, the
equipment light was on simulating it was working, but there was no current delivery.
The equipment was on for 30 min for active TENS and placebo TENS groups having the investigator next to
the patient throughout the application. For the control group, no electrodes were used, the investigator returned
to hospital bed 30 min after initial pain evaluation for a new pain evaluation.
At two different moments, the pain was assessed: before (M1) and post (M2) TENS intervention. We calculated
the difference between VAS values at the two application moments (M2-M1) for the three groups to evaluate the
effects of intervention.

Outcomes
Demographic and clinical characteristics (e.g., gender, age, disease, surgery and anesthesia type, pain site, medication
and pre-TENS pain intensity) were assessed at baseline assessment. Measurements of pain intensity occurred at the
baseline assessment and at the end of treatment. The primary outcome was pain intensity.

Statistical analysis
Descriptive statistical tests were used to present participant characteristics. We used, two tests: Shapiro-Wilk
and Levene in order to confirm normality and homoscedasticity of variables, respectively. The moments before
application of TENS (M1), post intervention (M2) and difference between the values at M2 and M1 (M2-M1)
were compared among the groups. For M1, M2 and difference between M2 and M1, the ANOVA One way and
Bonferroni post hoc were used. We used a significance level of 5%.
For the intergroup analysis, we calculated the Cohen’s d values in order to obtain the effect sizes. The values
considered were: d <0.2 = trivial effect; 0.2–0.5 = small effect; 0.5–0.8 = moderate effect; >0.8 = large effect [37].
The evaluation and highlight of clinical relevance of the results were the focus of this analysis.
For evaluating clinical changes, we considered that a change of 2 points on the VAS was a relevant clinical change
and we calculated the percentage of patients who had an increase and decrease of pain intensity of 2 points [38,39].
There was statistician blinding.

Results
Baseline data
The baseline data of all groups were alike for the primary and secondary variable outcomes. The majority of
participants were women, with cholelithiasis disease diagnoses and the most painful area was the umbilical incision
surgical site in the three groups (Table 1). All participants were submitted to LC surgery with general anesthesia.

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Table 2. Intergroup analysis of pain measurement.


VAS Control (n = 26) Active TENS (n = 26) Placebo TENS (n = 26) p-value
Mean ± SD CI (95%) Mean ± SD CI (95%) Mean ± SD CI (95%)
M1 2.69 (±1.47) 2.10–3.29 3.13 (±1.63) 2.04–3.79 2.50 (±1.58) 1.86–3.13 0.336
M2 2.71 (±1.71)† 2.02–3.40 1.04 (±1.14)† 0.58–1.50 1.66 (±1.29) 1.14–2.18 0.000‡
† Bonferroni post hoc; the significance level is 0.05.
‡ ANOVA one way.
M1: Before application of TENS; M2: Immediately after TENS application; M2-M1: Difference between M2 and M1; SD: Standard deviation; TENS: Transcutaneous electrical nerve
stimulation; VAS: Visual analog scale.

Table 3. Effects of intervention for intragroup analyses of pain measurement.


VAS Active TENS vs control Active TENS vs placebo TENS Control vs placebo TENS
CI (95%) p-value Cohen’s d CI (95%) p-value Cohen’s d CI (95%) p-value Cohen’s d
M2 -2.67 to -0.80 0.000† 1.27 -1.62 to 0.24 0.192 -0.59 0.11–1.98 0.117 0.70
M2-M1 -2.89 to -1.44 0.000† 2.24 -2.04 to -0.59 0.003† 0.89 0.13–1.57 0.011† 0.96
† ANOVA one way; the significance level is 0.05; Cohen’s d ⬍0.2 = trivial effect; 0.2-0.5 = small effect; 0.5-0.8 = moderate effect; ⬎0.8 = large effect.
M1: Before application of TENS; M2: Immediately after TENS application; M2-M1: Difference between values of VAS in M2 and M1; TENS: Transcutaneous electrical nerve stimulation; VAS:
Visual analog scale.

Table 4. Patient frequency analysis related to increase and decrease of pain intensity by visual analog scale.
Pain intensity Control group Placebo TENS group Active TENS group Control group Placebo TENS group Active TENS group
Patients (%) Patients (%) Patients (%) Clinical change (%) Clinical change (%) Clinical change (%)
Unchanged intensity 4 (15.4%) 5 (19.2%) 2 (7.7%)
Intensity increase 12 (46.2%) 1 (3.8%) 1(3.8%) 0 (0%) 0 (0%) 0 (0%)
Intensity decrease 10 (38.5%) 19 (73.1%) 22 (84.6%) 1 (3.8%) 3 (1.5%) 14 (53.8%)
Total 26 (100%) 26 (100%) 26 (100%)
Clinical change (%) = % of patients who had a change of 2 points in VAS to increase or decrease.
TENS: Transcutaneous electrical nerve stimulation; VAS: Visual analog scale.

Intergroup analysis
The data were collected on the first postoperative day before (M1) and post (M2) TENS intervention. As routine,
after the second day postsurgery, patients were released. A significant difference among the three groups for pain
reduction by VAS was present (Table 2). Considering interpretations of statistical significance, we found a difference
only between active TENS versus control group at M2.

Intragroup analysis
When the difference between the values at M2 and M1 was assessed, a significant difference was present at: active
TENS versus control; active TENS versus placebo TENS; and control versus placebo TENS, with Cohen’s d
considered a large effect (Table 3).

Clinical changes analysis


For evaluating the clinical changes of TENS, first we calculated the change percentage of patients in relation to an
increase, decrease or absence of change in pain intensity. We considered that a change of 2 points in VAS was a
relevant clinical change and then we calculated the percentage of patients who had an increase and decrease of 2
points in VAS (Table 4).
We found a reduction of pain intensity in 84.6% of the patients and clinical changes were present in 53.8% of the
patients (decrease 2 points or more in VAS) in the active TENS group. In the placebo group, the decrease occurred
in 73.1% of patients and the percentage of clinical changes was 11.5%. Since it was only 1 day of intervention, there
were no harms or unintended effects. When evaluating clinical changes, active TENS showed a higher percentage
of patients with a pain decrease of two points or more.

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Discussion
In our study, we found significant pain reduction in the active TENS group in relation to placebo TENS and
control group when we analyzed the difference between M2 and M1, and the active TENS group had a greater
clinically relevant effect in all comparisons. When we analyzed only M2, the pain reduction was significant in active
TENS group versus control group. The active TENS group had a large clinically relevant effect over control group
and medium over placebo TENS group.
For clinical application of TENS, different parameters such as frequency, pulse width, intensities and duration
of stimulation are adjusted. Frequency of stimulation is classified as high frequency (75–150 Hz) or low frequency
(1–4 Hz), the pulse width usually varies from 40 to 300 ms. Either the sensory level TENS or motor level TENS
determines the intensity through patient’s response and it is usually increased to the maximal level tolerable by the
patient before discomfort [21]. For obtaining a proper benefit from TENS, the duration of stimulus should be at
least 30–60 min [17]. In our study, conventional TENS current (frequency of 150 Hz and a pulse width of 75 μs)
was used and the duration of stimulus was 30 min.
Postoperative pain is a frequent problem, although its intensity may vary according to a number of factors
(individual perception thresholds, emotional factors, type of surgery, etc.), it represents a concern for the medical
team and patients. From a clinical perspective, pain is considered an immediate postoperative complication and it
compromises mobilization, deep breathing, cough and convalescence [9]. The recognition and treatment of acute
pain is extremely important because approximately 50% of patients might have chronic persistent postsurgical
pain [40,41]. Furthermore, if there is inappropriate management of acute pain, there might be related increases in
costs of healthcare and a decrease in patients’ satisfaction [40].
If we considered postoperative pain, shorter hospitalization stays and postoperative recovery improvement, the
laparoscopic surgery shows better advantages compared with open surgery. However, postoperative pain next to
the incision site is still present in laparoscopic surgery [9,42]. Le Blac-Louvry et al. [43] found higher scores of
postoperative pain on open cholecystectomy (OC) patients than with LC patients at the first 24 h after surgery
(day zero) and both pain and medication consumption were reduced on days 1, 2 and 3 postsurgery. In that study,
the average pain intensity measured by VAS at the first 24 h in the LC group was 4.0 (0.2) and in the OC group
6.2 (0.2). The authors [43] did not describe the time at which pain measurements were taken.
Ekstein et al. [44] evaluated the magnitude of pain and analgesic requirement between LC and OC and concluded
that the post-LC patients with pain needed more doses of analgesics (33%) and also reported more intense pain
during the first 4 h after surgery. On the other hand, the OC patients needed more pain medication than LC
patients after 9 h postsurgery.
Authors who measured pain intensity using the VAS after cholecystectomies found values between 2.5 and 4.0 at
the first 24 h [16,32,43–47]. In this study, we measured pain intensity by VAS both before and after TENS application.
The values were between 2.5 and 3.0, in the three groups. We used only VAS values measured in the first 24 h after
surgery because the average hospital stay was 1.23 days, however, patients who stayed more than 1 day in hospital
continued receiving TENS when they had pain complaints.
Different from these two studies [48,49] which measured pain intensity before and after TENS application and
verified TENS effectiveness comparing only values after TENS among groups, we also calculated the difference
between VAS values before and after TENS application to evaluate the effect on pain relief. To compare those
values with ours, we calculated the difference between the values before and after TENS applications. De Santana
et al. [48] evaluated pain decrease after laparoscopic tubal ligation and the difference between pain intensity before
and after was 0.20 in placebo TENS, 2.6 in low TENS and 3.2 in high TENS. In post episiotomy pain relief,
Pitangui et al. [49] assessed high and low frequency TENS effect and the difference between the first and the fourth
evaluations was 4.27 for high frequency TENS, 3.34 for low frequency TENS and 0 in the placebo TENS group.
Silva et al. [16] found a difference of 0.4 in the placebo TENS group and 2.4 in the active TENS group for patients
who underwent LC. In our study, we reported reductions of 0.86 in the placebo TENS group and 2.08 in the active
TENS group. Analyzing the intervention effectiveness results using difference values from before and after the
interventions provides us information about the effect of TENS in reducing pain. For the patient, independently
from pain score, how much pain was reduced is the most important factor, since it is an individual perception. Pain
is always characterized as an unpleasant sensation.
When dealing with acute pain conditions, there has been a positive response in postoperative pain reduction
after using TENS. In these situations, TENS has not been used as the only treatment, but alongside a medication

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routine [21]. Freynet and Falcoz [50] conducted a systematic review to answer whether TENS usage is effective in
decreasing post-thoracotomy pain. They concluded that TENS benefits patients, not only when treating acute
post-thoracotomy pain, but also used along with analgesic medication in order to reduce recovery-room stay period
and to increase chest coughing tolerance, leading to better pulmonary ventilation functioning. Therefore, current
scientific evidence has demonstrated that when TENS is associated with postoperative analgesic medications, it is
considered safe and effective for postoperative pain relief and it improves patient recovery after thoracic surgery.
Studies with wide ranging intensity settings continue to be included in TENS clinical research and systematic
reviews. High-intensity TENS used with patient-controlled analgesia produced a significant decrease in the post-
operative analgesic requirement, which was related to the magnitude of the electrical stimulation for patients after
lower abdominal surgery [51]. A systematic review conducted by Claydon et al. [52] in order to establish TENS
parameter combinations for pain reduction, concluded that concurrent high intensity TENS has larger effects
(during and post). Thus, practitioners should attempt to use TENS according to each patient’s maximum tolerable
intensity.
The theory of pain gate control is one of the theories used to describe TENS analgesic effects. According to
this theory, afferent fibers of large diameter stimulation attenuates, on dorsal horn, the nociceptive stimulation [53].
The results of Levin et al. [54] demonstrate that conventional and acupuncture TENS resulted in the excitation of
mainly large-diameter A-α and A-β fibers and suggested that the pain alleviating effects of these two types of TENS
can be facilitated by similar peripheral afferent fibers activation.
TENS can also activate endogenous opioids and activate opioids receptors. This activation occurs in high and
low frequency stimulations [55]. Considering analgesics, the control of postoperative pain is done by the use of
opioids and nonhormonal anti-inflammatory drugs [10]. High frequency TENS opioid-mediated analgesia has been
validated in humans [56]. TENS analgesic effects involving endogenous opioid receptor stimulation showed that
high-frequency TENS was blocked by a high dose of naloxone [56]. This may lead to the conclusion that this
satisfactory effect of TENS analgesia on postoperative pain may decrease the use of drugs which tend to cause side-
effects, such as emesis and nausea [26].
The effectiveness of TENS on postoperative pain remains without much support in the literature because most
studies have methodological problems, such as small sample size, no randomization, and/or not fully blinded.
A systematic review published by Carrol et al. [57] excluded 19 clinical trials. The criteria of exclusion were
nonrandomization or inadequate randomization (13 reports); small sample size (3 reports) and/or other problems
with the methodology (3 reports). A total of 17 out of the 19 excluded reports had satisfactory results in acute
postoperative pain relief with the use of TENS. Kerai et al. [25] excluded 10 from 18 randomized clinical trials
(RCTs) with scores below 3 in the Oxford five-point scoring. From the 8 RCTs selected, all were randomized
and only three were double blinded. Johnson et al. [18] included 19 trials in their systematic review. A total of 17
had a high risk of bias due to sample size, 14 to blinding participants and 8 had an unclear risk of bias due to
randomization. According to Schulz et al. [58], the nonrandomized or inadequately randomized studies presented
an exaggerated estimative of up to 40% of treatment effect and the ones that were not completely blinded could
show exaggeration of up to 17%.
We performed a randomized, single-blinded (participant), placebo-controlled trial. The blinding of the therapist
was not possible because only one equipment was used and the therapist was responsible for the handling. The
placebo group blinding was performed as follows: the subjects were wired to the TENS unit the same way as the
subjects of the active TENS group were. Although the indicator was active emitting light and sound, there was no
electrical stimulation being delivered. This same blinding model of using the equipment without the current, only
with the light on, has been used by many authors [59–63]. Alternative methods of blinding using TENS placebo in
other studies were no batteries [64–66], batteries reversed [67,68] controls turned off [69,70], remote nonsegmental [71]
and subthreshold stimulation [72]. For blinding the therapists, some authors have used modified TENS equipment
in which there is current delivery for only 45 s. For this kind of study, two machines identified by number are
necessary. Although this kind of blinding model (no current) used in our study has been used by many authors,
we understand that this placebo TENS is not the ideal blinding model and it is a limitation of our study. We used
the nonactive placebo TENS in this study because there was no modified TENS (active placebo) available in the
hospital at the moment of data collection. We have recently acquired two new portable TENS devices (one active
TENS and the other an active placebo/transient sham TENS) and we are already carrying out trials with these two
pieces of equipment.

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TENS in postoperative pain relief Preliminary Communication

In relation to sample size, although it was considered small, this number is higher than the one defined by
the sample calculation. Besides, articles published on use of TENS for postoperative pain in cholecystectomy
patients have smaller number compared with our study (varying from 10 to 21 in each group) [12,16,46,73]. A lack of
statistically significant results may be the consequence of a small sample size, but results with clinical significance
are still present [37].
During our research, despite no current stimulation being delivered to the patient in the placebo TENS group,
we did find a significant decrease in pain when compared with the control group. This may be explained by the
fact that the examiner stayed close to the patient during the application, having conversations and interacting with
them, which may have had interfered with the results (Hawthorne effect). The relationship between patient and
examiner has psychological aspects involved, such as the placebo effect [74]. Besides this, when the patients are
aware that he/she is receiving treatment, this may result in adjustments to the effect of the treatment which also
contributes to the placebo effect [75]. The patient’s acceptance of the therapy offered, desire to be well, self-image
and available support system all influence the development of a positive reaction to the placebo. There is also
evidence that the placebo response can induce the production of endorphins which may also induce a positive
response, however, there seems to be room for additional studies [76].
Despite having a significant analgesic effect in placebo group versus control group, (difference between M2 and
M1 variables), when analyzing the active TENS group versus placebo group and active TENS group versus control
group, the active TENS group showed a greater analgesic effect. Kirk [77] and Musselman [78] concluded that an
indicator of clinical applicability can be explained by the magnitude effect. When analyzing the magnitude effect
of TENS in active and placebo groups, there was a difference in statistics between the two groups, pointing out a
predominance of the active TENS group. The magnitude was considered large when the effect size was analyzed. A
larger difference between the groups can be interfered by a great magnitude effect, thus, a greater clinical relevance of
results [78]. When comparing the active TENS to the placebo TENS and control groups, we reached the conclusion
that there was a larger decrease in pain and a greater effect of clinical relevance in the active TENS group.
When we analyzed the clinical changes in pain intensity of patients, the active TENS group showed a decrease
of 84.6% and relevant clinical changes were present in 53.8% of the patients (a decrease of 2 points more in VAS).
In the placebo group, the decrease occurred in 73.1% of patients and the percentage of clinical changes was 11.5%.
Although the percentages of patients who had a decrease in pain intensity were similar (84.6 and 73.1%), when
we analyzed the decrease of 2 points on the VAS, in the active TENS group this decrease occurred in 53.8% of the
patients compared with 11.5% of placebo group. Thus, this information is important for physiotherapists’ clinical
decision. Is a decrease of 2 points on the VAS for 53.8% of patients enough to use TENS for postoperative pain?

Limitations
The limitations of this study include: first, we used a nonactive placebo (no electric current delivery) thus, it was not
possible to blind the examiner. For ensuring that the patient would not distinguish active from passive equipment,
we used only one equipment and both groups received the same guidance. The patients were instructed that they
were not going to feel the TENS current due to accommodation sensation; second, we did not use a blinding
questionnaire at the end of the trial so it was not possible to assess the effectiveness of blinding; third, the presence
of the investigator by the patient’s side, interacting and talking with them throughout the process (Hawthorne
effect), may have interfered with the result (confounding effect); and fourth, although the sample size of this study
was greater than similar studies, it can be considered small for a clinical trial.

Conclusion
We concluded that active TENS group was more efficient than placebo TENS and control for relieving pain in
patients who underwent LC. The active TENS presented a larger decrease in pain and a greater percentage of
relevant clinical changes compared with the placebo TENS group.

Financial & competing interests disclosure


This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nı́vel Superior – Brasil (CAPES) – Finance
Code 001. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial
interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.

future science group www.futuremedicine.com 243


Preliminary Communication Borges, de Oliveira, Antonelli, Silva, Crema & Fernandes

Clinical trials
Number of the local ethics committee: 1135/2008. Update number of the local ethics committee: 2.448.177; CAAE:
79628617.0.0000.5154; Brazilian Clinical Trial (REBEC): RBR-6cgx2k; UTN number: U1111-1207-7652.

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