Determining the Variable Factors in Cutaneous Perception of Vibratory Stimulation
Phase: NA
Conditions: Pain, Acute, Anesthesia, Local, Dermatology/Skin - Other
Sponsor: University of Pittsburgh

TITLE: Variable Perceptions of Cutaneous Stimuli  
PRINCIPAL INVESTIGATOR: Bryan Carroll, MD, PhD  
CO-INVESTIGATORS: Rashek Kazi, MD, PhD; Panayiota Govas, M.D., M.Sc.Med 
NCT: NCT03467685  
Protocol Date: 05/21/2018 
 
 

Scientific Background 
 
Previous work has quantified the effects of using non-noxious stimuli, specifically vibration, in 
reducing the pain of procedures. Work from the project PI Bryan Carroll (1) as well as Kenneth 
Beer (2) have detailed the ease and practical use of handheld vibration devices during in office 
procedures. Several other studies have also noted improved patient comfort with noxious 
stimulation after applying brief vibration. This has been studied in in office lip filler injection 
(3), botulinum toxin (4), and lip augmentation (5). Further, these studies have shown that not 
only does the approach provide significant analgesic control, patients opt to repeat use of 
vibration in future procedures at a rate of over 90% (5).  
 
Mechanistically, the basis for this approach lies in the "gate-control of pain" theory. Established 
by Melzack and Wall, gate-control theory postulates that non noxious stimuli such as vibration 
are detected by a specific subset of cutaneous nerve fibers known as a-beta fibers. This signal is 
rapidly transferred to the central nervous system and processed. By activating these fibers, there 
is a second set of signals which inhibits the activation of another set of cutaneous nerve fibers 
known as A-delta and C fibers. These fibers normally transmit painful signals, both acute and 
chronic. Through this activation-inhibition model, we intend to effectively limit the degree to 
which noxious stimuli is felt in the outpatient procedural setting (6). 
 
1. Gresham, Katherine A. MS; Carroll, Bryan T. MD, PhD. A Simple Elastomer-Pad Vibratory 
Dampener to Maximize Pain Control of Injections in Patient's Undergoing Dermatological 
Surgery. Dermatologic Surgery: June 2016 - Volume 42 - Issue 6 - p 788–790 
 
2. Beer, Kenneth R. MD. Commentary on a Simple Elastomer-Pad Vibratory Dampener to 
Maximize Pain Control of Injections in Patients' Undergoing Dermatological Surgery. 
Dermatologic Surgery: June 2016 - Volume 42 - Issue 6 - p 790. 
 
3. Sharma P, Czyz CN, Wulc AE. Investigating the efficacy of vibration anesthesia to reduce 
pain from cosmetic 
botulinum toxin injections. Aesthet Surg J. 2011;31(8):966-971 
 
4. Mally P, Czyz CN, Chan NJ, Wulc AE. Vibration anesthesia for the reduction of pain with 
facial dermal filler 
injections. Aesthetic Plast Surg. 2014;38(2):413-418. 
 
5. Guney K, Sezgin B, Yavuzer R. The Efficacy of Vibration Anesthesia on Reducing Pain 
Levels During Lip Augmentation: Worth the Buzz?. Aesthet Surg J. 2017 Oct 1;37(9):1044-
1048. doi: 10.1093/asj/sjx073. 
 
6. Dickenson AH. Gate control theory of pain stands the test of time. Br J Anaesth. 
2002;88(6):755-757  
 
 

Study Objectives 
 
Determine how patients in an out-patient surgical setting interpret non-noxious stimulation, 
specifically focusing on vibration.  
 
Perception of cutaneous stimuli is critical in the diagnosis and treatment of many dermatological 
diseases. However, there is little understanding of how global sensations varies across 
populations.  
 
Specific aim 1: Variable perception and interpretation of a non-noxious stimulus. 
Hypothesis: Different patient populations will show subtle, if any, difference of non-noxious 
stimulation.  
Rationale: Historically, there is evidence citing differences in perception of acute noxious stimuli 
across age, history of exposure to pain, and gender. Little information is available regarding non-
noxious stimuli. In previous work from our group and validated by other researchers, patients are 
largely able to tolerate the non-noxious stimulation of vibration. Our aim here is to determine 
whether this tolerability and interpretation shows any difference across cohorts, specifically 
those in an outpatient surgical setting.  
 
Specific aim 2: Variable perception and interpretation of a noxious stimulus following a non-
noxious stimulus 
Hypothesis: Different populations will show a significant difference in perception of noxious 
stimulation 
Rationale: As previously cited, different cohorts of humans has a wide variety in how pain, both 
acute and chronic, is perceived. In this aim, we can identify how the noxious stimulus of an 
injection of anesthetic varies across populations in an out-patient surgical setting. Further, it is 
known that the application of vibration prior to needle injection significantly reduces the pain felt 
by the patient. This aim can determine how this change varies across different patient cohorts.  
  
 
 

Study Design and Methods 
 
This is a DESCRIPTIVE, RANDOMIZED, partially blinded study. 
 
Study design  
A randomized, partially-blinded, parallel-group clinical study of perception and 
interpretation of a non-noxious vibration stimulus compared to placebo (vibratory device in “off” 
mode) during syringe-mediated local cutaneous infiltration of anesthetic was performed. The 
protocol was approved by the University of Pittsburgh Institutional Review Board 
(PRO17110134) and conforms to the ethical guidelines of the Declaration of Helsinki.  
Participants 
All adults (18+) presenting for MMS, surgical excision, and/or other cutaneous cancer 
removal surgery at Falk Dermatologic Surgery Clinic affiliated with the University of Pittsburgh 
Medical Center (UPMC) were eligible for inclusion. Subject enrollment occurred during a 90-day 
period from April to June 2018. Eligible subjects were informed of the study 24-72 hours before 
treatment via phone call.  
Patients with expressed interest in the study were given more information on the day of 
study, including the risks and benefits of participating. Any subsequent questions were answered 
at this time. All participants were given a pre-procedural questionnaire and provided written 
informed consent. A follow-up phone call was conducted post-procedure. 
Participant Training  
Participants underwent a training session to answer trial questions (“What is your pain 
level?”) using the 11-point Numeric Rating Scale (NRS) as well as descriptive adjectives of 
sensation (“Can you describe the sensation you felt on your skin?”). The vibratory anesthetic 
device (VAD) was placed on a ‘training site’ approximately 5 cm away from their treatment site 

in the OFF mode for 15s (Figure 1). Participants were then asked to describe the sensation they 
felt on their skin as well as the NRS pain level experienced. This process was repeated with the 
VAD in the ON mode.  
During this time, patients who were unable to discern between the VAD ON and OFF 
modes, expressed NRS>0, could not communicate effectively, had a language barrier or were 
unable to follow instructions were excluded (Figure 2).  
Intervention 
The VAD is a 10cm, handheld, battery-operated device by Finever. When ON, the device 
oscillates at a continuous frequency of 100Hz. It is non-experimental and available for purchase 
over-the-counter. The device was customized by positioning a cotton ball at the tip with subsequent 
placement into a nitrile glove.  
The VAD, anesthetic injection and infiltration, and surgical procedure were all performed 
by a single, board-certified dermatologic surgeon (BTC). The anesthetic used in all cases was 
lidocaine hydrochloride 1% with epinephrine 1:100,000 and buffered with 8.4% bicarbonate 1:10 
(Hospira Inc.). The anesthetic was prepared and administered in a 3 ml syringe with a 30-gauge 
needle. Anesthetic was prepared the day of the procedure.  
Outcome measures 
Subjects’ pain was assessed using the validated 11-point NRS (0 = no pain, 10 = worst pain 
imaginable). Pain level was evaluated at multiple time-points; pre-anesthetic injection with 
stimulus (VAD ON/VAD OFF) at 0s and 5s; the timepoint of anesthetic injection at 15s (NRS) 
with stimulus (VAD ON/VAD OFF); and 5s post-infiltration with no stimulus present. Patients 
communicated their pain level verbally at the above timepoints. 
Relative change in NRS was calculated with the below: 

𝑅𝑒𝑙𝑎𝑡𝑖𝑣𝑒 𝐶ℎ𝑎𝑛𝑔𝑒= 100 ∗𝑁𝑅𝑆3456578 −𝑁𝑅𝑆:5478
𝑁𝑅𝑆3456578
 
From the findings of Olsen et al., MCID and SCID was defined as a relative change of 22-
56% and >57%, respectively.  
 
 

CONSENT TO PARTICIPATE IN A RESEARCH STUDY  
TITLE: Variable Perceptions of Cutaneous Stimuli  
PRINCIPAL INVESTIGATOR: Bryan Carroll, MD, PhD CO-INVESTIGATORS: Rashek Kazi, 
MD, PhD; Panayiota Govas, M.D., M.Sc.Med.  
Contact Information: (412) 864-2660  
 
Why is this research being done?  
The purpose of this study is to determine if the use of a vibration tool immediately before 
injection of anesthetic alters your feeling of pain during an injection.  
 
You are being asked to take part in this research study because you are a patient of Dr. Carroll’s 
who has been diagnosed with a skin cancer and are scheduled for excisional or Mohs surgery for 
treatment.  
 
If you decide to participate a study investigator will give you a questionnaire to provide baseline 
information about your medical history, it can be completed in the waiting room in under 20 
minutes. As part of your normal care you will be prepared for your surgical procedure. The only 
change to normal care would be right before you receive your anesthetic injection we will 
randomize (like the flipping of a coin) you to one of two groups. Group 1 will receive a small 
vibration with a handheld device that is applied to the skin for about 15 seconds Group 2 will 
have the device applied without vibration. During your procedure we will ask you to rate your 
pain level about 6 times. We will call you about 6 hours after the procedure and ask a short 
questionnaire, in addition to our normal postoperative questions.  
 
This is a very low risk study, but you should be aware of risks. There are standard risks with 
surgery. These will be explained to you along with your consent for surgery.  
 
There is also a risk of mild discomfort from the handheld vibration anesthetic device, however 
there is no evidence of this being the case. If at any point the vibration becomes intolerable, you 
can ask us to stop.  
 
The questionnaire will ask questions about your overall health, level of pain tolerance, and your 
use of pain medication, including opiates. This has a risk of being potentially embarrassing in 
terms of the social stigma related to such medications and expectations of pain tolerance. As a 
reminder, all answers will remain confidential.  
 
Any time information is collected, there is a small risk of breach of confidentiality. Your 
research data will be identified by a unique study number rather than your name and all measures 
allowed by law to protect your confidentiality will be taken by the research staff. This data will 
be protected behind a password protected firewall on UPMC servers. It will only be accessible to 
the above investigators.  
 
This study may not have any direct benefit for you today however the information will be used to 
understand which populations of patients may require additional support to reduce the pain 
associated with minor surgical procedures.  
 

Previous research has shown that some patients find a reduction in the pain of injection when the 
vibration tool is used. However, there is no guarantee that this will be the case for you. You will 
not be paid for participating in this study nor will your insurance company be billed for the 
research procedures if you agree to participant in this study. Research use of the data collected 
may lead to new inventions or products, but you will not receive any money or compensation 
from any inventions or products that might be developed in the future. There are no current plans 
to share the research data however if we decide to share data in the future the data will be de-
identified and your identity will not be shared.  
 
COMPENSATION FOR INJURY  
If you believe that the research procedures have resulted in an injury to you, immediately contact 
the Principal Investigator who is listed on the first page of this form. Emergency medical 
treatment for injuries solely and directly related to your participation in this research study will 
be provided to you by the hospitals of UPMC. Your insurance provider may be billed for the 
costs of this emergency treatment, but none of those costs will be charged directly to you. If your 
research-related injury requires medical care beyond this emergency treatment, you will be 
responsible for the costs of this follow-up care. At this time, there is no plan for any additional 
financial compensation. You do not, however, waive any legal rights by signing this form.  
 
Who will know about my participation in this research study? The information that you give us 
will be kept confidential. In addition to members of the research team, authorized representatives 
of The Research Conduct and Compliance Office, University of Pittsburgh and authorized 
representatives of the study sponsor may look at your research records to ensure that the study is 
being conducted properly. Your name will not appear in any report or publication.  
 
Is my participation in this research study voluntary? May I leave the research study if I choose 
to? Your participation in this research study is completely voluntary. You may leave the project 
at any time. Whether or not you take part in this research project or if you decide to leave the 
project after you have accepted to participate will not have any consequences whatsoever. All 
data collected up to the point of withdrawal may be used by the investigators.  
************************************************************************ 
VOLUNTARY CONSENT  
All of the above has been explained to me and all of my current questions have been answered. I 
understand that I am encouraged to ask questions about any part of this research study during the 
course of this study, and that such future questions will be answered by the researchers listed on 
the first page of this form. Any questions which I have about my rights as a research participant 
will be answered by the Human Subject Protection Advocate of the IRB Office, University of 
Pittsburgh (1-866-212- 2668). By signing this form, I agree to participate in this research study. 
A copy of this consent form will be given to me. ______________________________ 
______________________________ __________  
Participant Signature Participant Printed Name Date CERTIFICATION OF INFORMED  
 
 
CONSENT I certify that I have explained the nature and purpose of this research study to the 
above-named individual, and I have discussed the potential benefits and possible risks of study 
participation. Any questions the individual has about this study have been answered, and we will 

always be available to address future questions as they arise. 
________________________________ _____ ___________________________________ 
_______ Signature of Person Obtaining Consent Role Printed Name of Person Obtaining 
Consent Date 
 
 
 
 
 

Eligibility Criteria 
 
What is the age range of the subject population? 
 
18 and older, all patients presenting for Mohs or Excisional Surgery with Dr. Carroll at UPMC 
Dermatologic Surgery  
Enrolling Pitt medical students 
  
What is their gender? 
 
*  Both males and females  
 
 Provide a justification if single gender selected: 
 
Will any racial or ethnic subgroups be explicitly excluded from participation? 
 
*  No   
 
For studies conducted in the U.S., do you expect that all subjects will be able to comprehend 
English? 
 
*  Yes  
 

 
Statistical Considerations 
 
Unpaired 2-tailed Student’s t-test was used for univariate analysis of all variables for 
comparison of NRS means. A threshold for significance was set at p < 0.05. All values collected 
were analyzed to report mean values ± standard error from the mean.  
 
Multivariate linear regression analysis was used to compare categorical variables (age, 
sex, and treatment site). Multivariate analysis of the overall cohort identified p<0.2 for age, sex, 
and treatment site. All further subgroup analysis was performed using multivariate analysis with 
a threshold for significance set at p<0.05. All statistical analyses were calculated by RK with 
Igor Pro (Wavemetrics, version 8) and STATA (StataCorp, version 13) software and confirmed 
with a consulting statistician (KMR).