The Efficacy of Transcutaneous Electrical Nerve Stimulation Versus Local Anaesthetic Cream in Alleviating the Pain of Local Anaesthetic Injections in Adults - A Randomised Controlled Trial
Phase: NA
Conditions: Donor Site Complication, Skin Graft
Sponsor: University Hospitals, Leicester

 
                                  
 
 
             
  TENS-LA 
 
                     
                 Transcutaneous Electrical Nerve Stimulation for Local Anaesthesia 
 
 
Clinical Trial Protocol 
 
 
The efficacy of Transcutaneous Electrical Nerve Stimulation versus local anaesthetic cream in          
alleviating the pain of local anaesthetic injections in adults - A Randomised Controlled Trial 
 
 
 
 
 
 
IRAS Project ID: 256620 
 
Protocol Version 1.0 
 
Date: 29/10/2018 
 
Sponsor: University Hospitals of Leicester 
 
Sponsor Number EDGE 113691 
 
 
 
 
 
 

 
2 
                                                        
SIGNATURE PAGE 
The undersigned confirm that the following protocol has been agreed and accepted and that the 
Chief Investigator agrees to conduct the study in compliance with the approved protocol and will 
adhere to the principles outlined in the Declaration of Helsinki, the Sponsor’s SOPs, and other 
regulatory requirement. 
I agree to ensure that the confidential information contained in this document will not be used for 
any other purpose other than the evaluation or conduct of the investigation without the prior 
written consent of the Sponsor 
I also confirm that I will make the findings of the study publically available through publication 
or other dissemination tools without any unnecessary delay and that an honest accurate and 
transparent account of the study will be given; and that any discrepancies from the study as 
planned in this protocol will be explained. 
 
For and on behalf of the Study Sponsor: 
Signature:  
...................................................................................................... 
 
Date: 
....../....../...... 
Name (please print): 
...................................................................................................... 
 
 
Position: 
...................................................................................................... 
 
 
 
Chief Investigator: 
Signature: 
...................................................................................................... 
 
Date: 
....../....../...... 
Name: (please print): 
...................................................................................................... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
3 
TABLE of Contents.                                                                                                                                   
 Signature Page 
 2 
 Table of Contents  
 3 
 Summary 
 4 
1 INTRODUCTION 
 6 
2 TRIAL DESIGN 
 
2.1 Overview 
 9 
2.2 Settings 
10 
2.3 Sample Size 
10 
2.4 Eligibility 
10 
2.5 Ethical Considerations, Information Giving and Written Informed Consent 
11 
2.6 Randomisation 
11 
2.7 Trial Intervention 
11 
2.8 Adverse Events 
13 
2.9 Outcome Assessment 
13 
2.10 Data Collection and Management 
13 
2.11 Monitoring 
13 
2.12 Analysis 
14 
3 TRIAL ORGANISATION 
 
3.1 Sponsorship 
14 
3.2 Protocol Committee 
14 
3.3 Collaborator’s Responsibilities 
15 
3.4 Publication and Dissemination of Results 
16 
4 LIST OF ABBREVATIONS 
16 
5 REFERENCES 
16/17 
6 APPENDICES 
18 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
4 
SUMMARY 
 
 
Full Title of Study 
The efficacy of Transcutaneous Electrical Nerve Stimulation versus local anaesthetic 
cream in alleviating the pain of local anaesthetic injections in adults - A Randomised 
Controlled Trial 
 Short title 
Transcutaneous Electrical Nerve Stimulation for Local Anaesthesia 
Trial Acronym 
TENS-LA 
EDGE ID:  
 
Protocol version 1.0 dated 29/10/2018 
Sponsor:  University Hospitals of Leicester 
Background 
Even a simple local anaesthetic procedure is associated with much anxiety for the patient 
involved. This is compounded by the process of local anaesthetic injection which 
involves not only the pain of the needle puncture but the stinging sensation as the local 
anaesthetic is infiltrated into the site. Many methods of easing this pain have been used 
such as using smaller gauge needles, slow infiltration, buffering the anaesthetic and prior 
application of local anaesthetic creams. 
There has been a lot of research conducted in dentistry which has shown the 
effectiveness of Transcutaneous Electronic Nerve Stimulation (TENS) as an anaesthetic 
agent1. But the research has not extended to other fields of surgery such as in minor local 
anaesthetic cases.  
Aim  
TENS-LA trial will be able to provide evidence regarding the possible efficacy of TENS 
as a local anaesthetic and its ability to alleviate the pain associated with local anaesthetic 
injection. The effectiveness will also be compared to that of local anaesthetic cream 
which is being used at present prior to local anaesthetic injections. 
Outcome 
Primary Outcome: The primary outcome is pain of local anaesthetic injection after 
application of TENS or LA cream as measured by two Numeric Pain Rating Scale 
Secondary Outcomes: Changes in blood pressure and pulse rate in response to injection 
of local anaesthetic 
Trial Design 
A prospective randomised controlled trial. 
 
 
 
 

 
5 
Diagnosis and Inclusion/Exclusion Criteria 
Adults 18-90 years of age undergoing a split skin graft harvest from the thigh under local 
anaesthesia will be included 
• who do not have a pacemaker or ICD 
• who are not pregnant 
 - with no history of epilepsy, aneurysm 
 - with no history of allergy to local anaesthetic or TENS electrodes 
Test device and Mode of usage 
A hand-held battery-powered CE-approved TENS device will be used. Eligible patients 
who have been randomised to the test arm of the study will have the electrodes attached 
to the area adjacent to the skin graft donor site 30 minutes before injection of local 
anaesthetic. 
Setting 
The trial will be conducted in Leicester Royal Infirmary, UK 
Duration of treatment 
The TENS treatment is over a minimum period of 30 minutes from attachment of 
electrodes to administration of local anaesthetic. 
The LA cream treatment is over a minimum period of 60 minutes from application of the 
cream to administration of local anaesthetic. 
Evaluation Criteria 
The effectiveness of the treatment is assessed using two Numeric Pain Rating Scale in 
the study and control groups. Pulse rate and Blood Pressure monitoring will be carried 
out as an objective measurement of the response to pain. 
Planned trial start date 
1st May 2019 
Planned date of last outcome 
30th April 2020 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
6 
 
1. INTRODUCTION 
 
 
Background 
 
Even a simple local anaesthetic procedure is associated with much anxiety for the patient 
involved. This is compounded by the process of local anaesthetic injection which 
involves not only the pain of the needle puncture but the stinging sensation as the local 
anaesthetic is infiltrated into the site. Many methods of easing this pain have been used 
such as using smaller gauge needles, slow infiltration, buffering the anaesthetic and prior 
application of local anaesthetic creams. 
 
Study objectives and significance 
 
There has been a lot of research conducted in dentistry which has shown the effectiveness 
of Transcutaneous Electronic Nerve Stimulation (TENS) as an anaesthetic agent1. But the 
research has not extended to other fields of surgery such as in minor local anaesthetic 
cases.  
TENS has been approved by CE as a method of pain alleviation1. The TENS-LA trial will 
be able to provide reliable evidence on the possible effectiveness of TENS in alleviating 
pain of local anaesthetic injections and also how it compares with local anaesthetic cream 
for this purpose. If TENS is found to be effective, it can be used as a simple and safe 
device in minor surgical procedures to take away the most dreaded part of the procedure- 
the pain of injections. 
 
TENS is a method of electrical stimulation to provide a degree of pain relief by 
stimulating either the pain gate mechanism and/or the internal opioid system.  
It is a non-invasive method with hardly any side effects. The most common side effect 
reported is allergic reaction (2-3%) to the electrodes, gel or the tapes used for fixing the 
electrodes. 
 
The intensity of current used ranges from 0-80mA into 500 Ohm load. The aim is to 
depolarise the sensory nerves and for this purpose the small strength provided by the 
machine is sufficient. This is delivered in pulses. To be clinically effective, the pulse 
ranges from 2-200 pulses per second (pps) or Hertz (Hz). The duration of each pulse 
(pulse width) may vary from 50 to 300 microseconds (µs). 
There are two primary pain relief mechanisms: the pain gate mechanism and the 
endogenous opioid system. 
The gate control theory was proposed by Melzack and Wall in 19652. By activation of the 
Aβ sensory fibres (large fibres) with non-noxious stimuli the inhibitory interneurons in 
the dorsal horn are activated and the transmission of the noxious stimulus from the C 

 
7 
fibres (small fibres) inhibited. Thus, selective enhancement of input in large fibres shuts 
the Pain Gate band diminishes any ongoing pain3. 
 
The alternative mechanism of pain relief by TENS is that it stimulates the release of 
endogenous opioids in the spinal cord. Low frequency and high frequency TENS 
function through activation of mu and delta opioid receptors respectively4,5. 
 
TENS was used by Wall and Sweet6 on patients experiencing pain, increasing the voltage 
till tingling was experienced in the area and resulted in relief of pain during the 
stimulation and for 30 minutes after. 
 
The intensity or amplitude of TENS is directly related to the positive effect- a strong 
intensity (barely comfortable) provides significant analgesic effect7. 
A systematic review and meta -analysis on the effectiveness of TENS on post-operative 
analgesia by Bjordal et al8 concluded that there is significant reduction in analgesic 
consumption for post-operative pain when TENS is administered with a strong intensity 
at an adequate frequency in the area. 
 
 
TENS was found to be a good alternative to local anaesthetic in children requiring 
restorative dental procedures in many studies9,10. 
 TENS was found to be more effective than local anaesthetic gel prior to inferior alveolar 
block injection in children in reducing the pain of injection in a study by Choudhari et al11 
which confirmed the findings from a similar study earlier by Meechan et al12. 
TENS was found to be almost equally effective as 2% local anaesthetic injection during 
minor paediatric dental procedures and more comfortable and preferred by 93.3% of the 
patients over the local anaesthetic in a study by Dhindsa et al13. 
 
 
Objectives 
The primary aim of this study is to evaluate the possible effectiveness of TENS in 
reducing the pain associated with local anaesthetic injection and to compare it with the 
use of topical anaesthetic cream. The hypothesis is that TENS is effective in 
alleviating/reducing the pain of local anaesthetic injection and more or equally effective 
compared with local anaesthetic cream for this purpose. 
 
 
 
 
 
 
 
 

 
8 
 
Methods and design 
 
The study is planned as a randomised control trial with 2 arms: 
 
1- The control group will have a local anaesthetic cream EMLA (Eutectic Mixture of 
Local Anaesthetics) applied for a minimum period of 60 minutes before injection of 
local anaesthetic 
 
2- The study group will have TENS applied for a minimum period of 30 minutes before 
injection of local anaesthetic 
 
Two electrodes will be placed - one proximal and the other distal to the area marked for harvest 
of skin graft on the thigh a distance of 10 cm. 
Conventional treatment mode Programme 1 will be used with a rate of 80Hz -100Hz and pulse 
width of 200 micro seconds. The intensity will be gradually increased till patient experiences 
steady continuous stimulation but no muscle contraction. This is maintained for a period of 30 
minutes after which the local anaesthetic injection is carried out. 
 
Rationale 
Though there have been several publications on the benefits of TENS as a local 
anaesthetic and also to reduce the pain of local anaesthetic injections, such a research is 
lacking in the surgical specialties. This trial would help to fill in this gap in evidence and 
help to make better evidence-based decisions. 
If found to have a statistically significant benefit over the use of EMLA to alleviate the 
pain of local anaesthetic injection, TENS will be the way forward for minor operations 
for the purpose. The most dreaded part of the procedure for the patient is made more 
tolerable. 
 
 
 
 
 
 
 

 
9 
2. TRIAL DESIGN 
 
2.1 OVERVIEW 
Flow Chart: Study Overview 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                                   Eligibility 
Adult undergoing a split skin graft harvest  
- Between 18 and 90 years of age 
- Not having a pacemaker or ICD 
- Not pregnant 
- Not mentally incapacitated 
- No history of epilepsy or aneurysm 
- No history of allergy to LA or TENS electrodes 
- No history of undiagnosed skin/pain conditions 
- Not taking part in other trials 
             Appropriate CONSENT process 
                        RANDOMISE 
                        (TENS/EMLA) 
               BP and pulse recording 
Apply TENS/EMLA 
Complete Numeric pain rating scale and BP 
and Pulse chart 
Administer LA injection (30 minutes after 
TENS, 60 minutes after EMLA) 
Record BP and Pulse before injection. 

 
10 
TENS-LA trial is a randomised control trial to assess the possible efficacy of 
Transcutaneous Electrical Nerve Stimulation (TENS) on eliminating or reducing the pain 
of local anaesthetic injection for minor surgical procedures. Comparison is done with a 
mixture of local anaesthetic cream (EMLA) which is used at times for the same purpose. 
Though local procedures are carried out in various parts of the body, this trial will be 
conducted specifically on patients undergoing a split skin graft harvest from the thigh. 
Patients who meet the eligibility criteria and are willing to participate will be randomised 
to receive either TENS or EMLA. 
 
Eligible patients: Adult patients listed to have a split skin graft harvest under local 
anaesthesia will be assessed for eligibility for taking part in the trial.  
 
 
2.2 SETTINGS 
  
The study will be conducted at Leicester Royal Infirmary by the Department of Plastic 
Surgery.  
 
2.3 SAMPLE SIZE 
 
The study is designed to detect a difference of 3 units in pain scale between the 2 groups 
at 0.05 significance level and 90% power. We assume the standard deviation as 3 and the 
number of participants in each group has been calculated as 22.  The total number of the 
patients including both arms of the trial will be 44. 
 
 
2.4 ELIGIBILITY CRITERIA 
 
Both interventions will be carried out in adult patients. For the purpose of standardisation 
and avoiding the variations from different sites in the body, and different surgical 
procedures, the site will be the thigh in both groups which is the donor site for a split skin 
graft.  
 
Inclusion criteria: 
Adult patients aged 18 to 90 years undergoing a split skin graft harvest under local 
anaesthesia 
 
Exclusion criteria: 
Patients below 18 and above 90 years of age 
Patients with dementia or any other mental abnormalities who do not have the capacity to 
consent. 
Pregnant ladies 
Patients with pace maker or ICD 

 
11 
Patients with history of epilepsy or aneurysm 
Patients with history of allergy to local anaesthetic or TENS electrodes 
Patients with undiagnosed skin or pain conditions 
Patient taking part in other studies 
 
2.5 ETHICAL CONSIDERATIONS, INFORMATION GIVING AND WRITTEN 
INFORMED CONSENT 
 
 As outcome assessment involves a pain scale rating which has to be carried out by 
patient and requires that the patient be capable of providing this rating, the trial will not 
involve patients who are mentally incapacitated. 
 
The investigator will explain to the patient that the trial is conducted to assess the 
effectiveness of TENS in alleviating the pain associated with local anaesthetic injection 
in comparison to EMLA and such trials have been conducted as research elsewhere and 
are safe. An information sheet will be provided and the patient is given the option to 
participate in the study. If they wish to be included, a written informed consent will then 
be taken. If the patient does not wish to enter the study, their choice will in no way affect 
their planned surgical treatment and post-operative care which will be carried out as per 
departmental standards. 
 
 
2.6. REGULATORY REVIEW 
Before any patients are enrolled, the Chief Investigator/Principal Investigator will ensure 
that appropriate approvals are in place. For any amendment to the study, the Chief 
Investigator in agreement with the Sponsor will submit information to the appropriate 
body in order for them to issue approval for the amendment. 
 
 
2.7 RANDOMISATION 
 
After obtaining informed consent patients will be randomised to two groups using codes 
generated by web-based randomisation system- Research Randomizer. This is a free 
resource for researchers. The website is http://www.randomizer.org 
The numbers generated will be placed in separate sealed envelopes by the department 
secretary and made available to the investigators. 
 
2.8 TRIAL INTERVENTION 
 
On the day of procedure, either the Chief Investigator or Investigator will see the patient 
in the Theatre Arrivals area and have a full discussion on the details of the trial and will 
answer all their questions.  Patients willing to take part and are within the inclusion 

 
12 
criteria and does not have any of the exclusion criteria will be randomised to either the 
study group or the control group after obtaining informed consent. 
 
The trial group will have the TENS to the area planned for injection for at least 30 
minutes before injection of the local anaesthetic. 
The control group will have EMLA 5% applied on the site planned for local anaesthetic 
injection and after a minimum period of 1 hour, will be removed and immediately 
injected with the same anaesthetic solution (this is already a procedure practiced by some 
of the surgeons). 
Pain perception will be evaluated using two Numeric Pain Rating Scales in the study and 
control groups- one to assess the pain of needle penetration and the second to assess the 
pain of local infiltration.  The Numeric pain scale is filled in by the doctor as indicated by 
the patient. Pulse rate and Blood Pressure monitoring will be carried out as an objective 
measurement of response to pain (these are routinely recorded when patient is in the 
theatre for a procedure). Patient involvement in the study ends at this point. 
 
Analysis of the outcome will be done at the end of the trial period. 
 
Description of device 
 
The TENS unit comprises of an  
(1) Electric pulse generator which is battery-operated and programmable for pulse rate, 
width and intensity. 
(2) Lead wires connecting the unit to electrodes 
(3) Electrodes which consists of silicone rubber and adhesive to attach to skin surface. 
 
 
Specifications of the unit to be used. 
 
The device to be used in the trial is Neurotrac TENS Unit 
 
Power supply 
: PP3 Alkaline battery, 9 volts 
Pulse rate 
 
: 80Hz -100Hz 
Pulse width  
: 50 – 300 microseconds 
Amplitude 
 
: 0-80mA (500 Ohm load) 
Type  
 
: Continous 
 
Contraindications 
 
1. In patients with pacemakers or implantable cardioverter-defibrillators (ICDs)14. 
This is of utmost significance for use in thoracic area as there will be interference 
with the electrical impulses generated except in fixed rate pacemakers. 
 

 
13 
2.   Epileptic patients - as there is a risk of triggering a seizure. 
 
3.  Patients with history of aneurysm. TENS stimulates peripheral blood flow and 
hence can be problematic in such cases. 
 
4. Pregnant patients. There are no definitive side effects and some studies15 have 
demonstrated the effectiveness and safety of TENS use during pregnancy. But as 
such it has not been approved for use in pregnancy.  
 
5. By patients with undiagnosed skin or pain conditions 
 
 
2.9 ADVERSE EVENTS 
 
 EMLA Cream and TENS have a well-documented safety profile. The commonest side 
effect for TENS reported is allergic reaction (2-3%) to the electrodes, gel or the tapes 
used for fixing electrodes. Any adverse events/ reactions to either EMLA or TENS 
machine will be collected and reported in the Case Report Form. Due to the minimal risk 
presented, Serious Adverse Events will not be collected for this study.  
 
2.10 OUTCOME ASSESSMENT 
 
Pain perception will be evaluated using two Numeric Pain Rating Scales in the study and 
control groups. One scale will assess the pain caused by needle piercing the skin and the 
second will do so for the pain caused by infiltration of local anaesthetic agent. 
Pulse rate and Blood Pressure monitoring will be carried out as an objective measurement 
of response to pain. 
2.11 DATA COLLECTION AND MANAGEMENT 
The trial will be conducted at Leicester Royal Infirmary and data collection done by 
investigators on site. Data on eligibility will be available in the case report form. Other 
data will include consent form, outcome assessment forms and data on adverse events/ 
reactions. Paper data will remain at the trial site itself in locked cabinet and will only be 
accessed by the investigators. For the purpose of analysis data will be transcribed to excel 
spreadsheet. Data will be used only in accordance with the data protection act and ethical 
considerations. Any data analysed or seen by other parties will be pseudo-anonymised by 
allocating a number to everyone. 
2.12 MONITORING 

 
14 
University Hospitals of Leicester NHS Trust, as Sponsor, operates a risk based 
monitoring and audit program to which the study will be subject. The trial will collect 
data on any adverse event/ reaction. All trial related documents will be kept for at least 
five years after completion of the trial. 
2.13 ANALYSIS 
The analysis will assess the effectiveness of TENS in alleviating the pain of local 
anaesthetic injection with the differentiation of needle and infiltration pain and also 
compare the TENS with EMLA. It is expected that TENS will alleviate or bring about a 
significant reduction in the pain associated with injection of local anaesthetic and will be 
better or as effective as EMLA in this aspect. This is the hypothesis being examined in 
this trial.  
Pain perception will be evaluated using two Numeric Pain Rating Scales in the study and 
control groups. Pulse rate and Blood Pressure monitoring will be carried out as an 
objective measurement of response to pain. 
The tabulation of the results will be done by the research team after transcribing to an excel 
spreadsheet and the fully anonymised data will be analysed statistically by the biostatistician at 
The University of Leicester. 
Summary statistics of 2 groups will be presented. Median score, lower and upper quartile 
and minimum and maximum scores will be given for each group. Two groups will be 
compared using Mann Whitney test. 
 
3 TRIAL ORGANISATION 
3.1 SPONSORSHIP 
The TENS-LA trial will be sponsored by University Hospitals of Leicester NHS Trust. 
 
3.2 PROTOCOL COMMITTEE 
The protocol committee consists of the following investigators. 
CHIEF INVESTIGATOR 
CLINICAL EXPERTS 
Ms Rajshree Jayarajan 
Specialty Doctor 
Department of Plastic Surgery 
Mr Graham Offer 
Clinical Lead and Consultant 
Department of Plastic Surgery 

 
15 
University Hospitals of Leicester 
UK 
 
University Hospitals of Leicester 
UK 
 
Mr Nakul Patel 
Research Lead and Consultant  
Department of Plastic Surgery 
University Hospitals of Leicester 
UK 
INVESTIGATORS 
STATITICIAN 
Mr Reza Arya 
ST7 Specialist Registrar in Plastic 
Surgery 
Department of Plastic Surgery 
University Hospitals of Leicester 
UK 
 
 
 
 
Dr Maria Viskaduraki 
BBASH Facility Manager-Biostatistics 
Bioinformatics and Biostatistics Hub 
College of Medicine, Biology and 
Psychology 
University of Leicester 
UK 
Mr Avinash Deodhar 
Locum Specialty Doctor 
Department of Plastic Surgery 
University Hospitals of Leicester 
UK 
 
 
3.3 COLLABORATOR’S RESPONSIBILITIES 
  
       The responsibilities of the chief investigator will be detailed in advance of starting 
the trial and will include: 
• Ensure all necessary approvals are in place prior to starting the trial 
• Delegate responsibilities related to the trial only to suitably qualified and trained 
personnel 
• Ensure that patients fulfilling eligibility criteria and considered for the trial 
• Ensure patients are given adequate information regarding the trial and informed 
consent obtained 
• Ensure that the documentation is up to date 
• Ensure that all adverse effects related to the trial are promptly reported 
• Ensure that the trial is conducted in accordance with the ICH GCP and fulfils local and 
national guidelines. 
• Hold the responsibility for archiving the original trial documents for 5 years after end 
of trial 

 
16 
 
 
 
3.4 PUBLICATION AND DISSEMINATION OF RESULTS 
 
The trial protocol and the final results of the trial will be published in established peer-
reviewed journal. Links to the publication will be provided in all applicable trial registers. 
In addition, participants of the trial will be informed of the trial results if requested. 
 
 
4 LIST OF ABBREVIATIONS 
 
AE 
Adverse Event 
AR 
Adverse Reaction 
BP 
Blood Pressure 
EMLA 
Eutectic Mixture of Local Anaesthetics 
GCP 
Good Clinical practice 
ICD 
Implantable Cardioverter Defibrillators 
LA 
Local Anaesthetic 
PR 
Pulse Rate 
TAA 
Theatre Arrivals Area 
TENS 
Transcutaneous Electronic Nerve Stimulation 
UK 
United Kingdom 
 
 
5. REFERENCES 
 
1.  Kasat V, Gupta A, Ladda R, Kathariya M, Saluja H, Farooqui A-A. 
Transcutaneous  
   electric nerve stimulation (TENS) in dentistry- A review. 
Journal of Clinical and     Experimental Dentistry. 2014;6(5):e562-e568. 
doi:10.4317/jced.51586. 
 
2. Melzack R, Wall PD. Pain mechanisms: a new theory. Science. 1965;150:971–
979 
 
3. Mendell LM. Constructing and Deconstructing the Gate Theory of Pain. Pain. 
2014;155(2):210-216. doi:10.1016/j.pain.2013.12.010 
 

 
17 
4. Sluka KA, Deacon M, Stibal A, Strissel S, Terpstra A. Spinal bloc- kade of opioid 
receptors prevents the analgesia produced by TENS in arthritic rats. J Pharmacol 
Exp Ther. 1999;289:840-6. 
 
5. Kalra A, Urban MO, Sluka KA. Blockade of opioid receptors in rostral ventral 
medulla prevents antihyperalgesia produced by transcutaneous electrical nerve 
stimulation (TENS) J Pharmacol Exp Ther. 2001;298:257–63. 
 
6. Wall PD, Sweet WH. Temporary abolition of pain in man. Science. 
1967;155:108–109. 
 
7. Sluka KA, Bjordal JM, Marchand S, Rakel BA. What Makes Transcutaneous 
Electrical Nerve Stimulation Work? Making Sense of the Mixed Results in the 
Clinical Literature. Physical Therapy. 2013;93(10):1397-1402. 
doi:10.2522/ptj.20120281. 
 
8. Bjordal JM, Johnson MI, Ljunggreen AE. Transcutaneous electrical nerve 
stimulation (TENS) can reduce postoperative analgesic consumption: a meta-
analysis with assessment of optimal treatment parameters for postoperative pain. 
Eur J Pain. 2003;7:181–188 
 
 
9. Varadharaja M, Udhya J, Srinivasan I et al.Comparative clinical evaluation of 
transcutaneous electrical nerve stimulator over conventional local anesthesia in 
children seeking dental procedures: A clinical study. J Pharm Bioallied Sci. 2014 
Jul; 6(Suppl 1): S113–S117.doi:  10.4103/0975-7406.137407 
 
10. teDuits E, Goepferd S, Donly K, Pinkham J, Jakobsen J. The effectiveness of 
electronic dental anesthesia in children. Pediatr Dent. 1993 May-Jun;15(3):191-6. 
 
11. Choudhari SR, Parikrama SJ, Gaurav VK et al. Efficacy of transcutaneous 
electronic nerve stimulation in alleviating pain during inferior alveolar nerve block 
injections in pediatric dentistry. International Journal of Pedodontic Rehabilitation. 
2017;2(2): 69-72 
 
12. Meechan JG, Gowans AJ, Welbury RR. The use of patient‐controlled 
transcutaneous electronic nerve stimulation (TENS) to decrease the discomfort of 
regional anaesthesia in dentistry: A randomised controlled clinical trial. J Dent 
1998;26:417-20.  
 
13.  Dhindsa A , Pandit IK, Srivastava N, Gugnani N. Comparative evaluation of the 
effectiveness of electronic dental anesthesia with 2% lignocaine in various minor 

 
18 
pediatric dental procedures: A clinical study . Contemporary Clinical Dentistry. 
2011; 2.1: 27-30. 
 
14.  Burri H, Piguet V. UninTENSional pacemaker interactions with transcutaneous 
electrical nerve stimulation. Europace. 2009;11:283–284. 
doi:10.1093/europace/eup008. 
 
15. Keskin EA, Onur O, Keskin HL, Gumus II, Kafali H, Turhan N. Transcutaneous 
electrical nerve stimulation improves low back pain during pregnancy. Gynecol 
Obstet Invest. 2012;74(1):76-83. doi: 10.1159/000337720. 
 
6.APPENDICES 
 
Appendix 1: Patient Information Sheet 
Appendix 2: Informed Consent 
Appendix 3: Case Report Form 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
19