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Local and Regional Anesthesia 2018:11 9–13
Local and Regional Anesthesia Dovepress
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CLINICAL TRIAL REPORT
open access to scientific and medical research
Open Access Full Text Article
http://dx.doi.org/10.2147/LRA.S147288
Effect of warming anesthetic on pain perception
during dental injection: a split-mouth randomized
clinical trial
Pedro Christian Aravena1,2
Camila Barrientos1
Catalina Troncoso1
Cesar Coronado3
Pamela Sotelo-Hitschfeld4
1Department of Dentistry,
Universidad Austral de Chile, Valdivia,
Chile; 2Department of Dental Implant
Surgery, São Leopoldo Mandic School
and Dental Institute, Campinas, SP,
Brazil; 3Faculty of Health Science,
School of Medicine, Universidad
Autónoma de Chile, Santiago,
Chile; 4Department of Center for
Interdisciplinary Studies on Nervous
System (CISNe), Universidad Austral
de Chile, Valdivia, Chile
Background: The purpose of this study is to determine the effectiveness of warming anesthesia
on the control of the pain produced during the administration of dental anesthesia injection and
to analyze the role of Transient Receptor Potential Vanilloid-1 nociceptor channels in this effect.
Patients and methods: A double-blind, split-mouth randomized clinical trial was designed.
Seventy-two volunteer students (22.1±2.45 years old; 51 men) from the School of Dentistry at
the Universidad Austral de Chile (Valdivia, Chile) participated. They were each administered
0.9 mL of lidocaine HCl 2% with epinephrine 1:100,000 (Alphacaine®) using two injections in
the buccal vestibule at the level of the upper lateral incisor teeth. Anesthesia was administered
in a hemiarch at 42°C (107.6°F) and after 1 week, anesthesia was administered by randomized
sequence on the contralateral side at room temperature (21°C–69.8°F) at a standardized speed.
The intensity of pain perceived during the injection was compared using a 100 mm visual analog
scale (VAS; Wilcoxon test p<0.05).
Results: The use of anesthesia at room temperature produced an average VAS for pain of
35.3±16.71 mm and anesthesia at 42°C produced VAS for pain of 15±14.67 mm (p<0.001).
Conclusion: The use of anesthesia at 42°C significantly reduced the pain during the injection
of anesthesia compared to its use at room temperature during maxillary injections. The physi-
ological mechanism of the temperature on pain reduction could be due to a synergic action on
the permeabilization of the Transient Receptor Potential Vanilloid-1 channels, allowing the
passage of anesthetic inside the nociceptors.
Keywords: pain, dental anesthesia, maxillary, lidocaine, trigeminal nerve, clinical trial, TRP
channel
Introduction
The use of local anesthesia in dentistry is a critical component in dental treatment
given patients’ fear of injections and pain caused during the injection of anesthesia.1
This act causes inherent tissue damage during penetration of the needle and injection
of anesthetic fluid,2 releasing proinflammatory mediators and increasing the pressure in
the submucosal tissue that activates nociceptor terminals, sensitizing the puncture site.3
The methods studied to control this situation include the use of nerve block
injections, lower injection speeds at 1 cartridge/min4,5 and the compression of tissues
adjacent to the puncture site.5 However, all these methods are operator-dependent.
One method proven to reduce the perception of pain is to warm local anesthetics.6–8
Reports in dentistry are inconsistent. Rogers et al9 showed that the warmed anesthetic
injection was significantly more comfortable than one at room temperature. However,
Correspondence: Pedro Christian
Aravena
Rudloff Street 1640. Valdivia 5110474,
Chile
Tel +56 63 222 1205
Fax +56 63 229 3751
Email paravena@uach.cl
Journal name: Local and Regional Anesthesia
Article Designation: CLINICAL TRIAL REPORT
Year: 2018
Volume: 11
Running head verso: Aravena et al
Running head recto: Effect of warming anesthesia in pain perception
DOI: http://dx.doi.org/10.2147/LRA.S147288
This article was published in the following Dove Press journal:
Local and Regional Anesthesia
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Aravena et al
Oikarinen et al10 and Ram et al11 showed that the injection of
anesthetic at body temperature did not present any significant
differences in the subjective perception of pain.
A systematic review by Hogan et al12 decided on the
effectiveness of heating anesthetics to control pain during
the injection at various areas of the body, suggesting that
this effect be analyzed for dental anesthetic injections. This
effect would contribute to reducing the anxiety levels, thereby
causing greater comfort during treatment and a better dentist–
patient relationship.13,14
Therefore, the aim of this study is to determine the
effectiveness of the use of anesthesia at 42°C in the percep-
tion of pain during the administration of dental anesthesia
compared to its use at room temperature (21°C) during the
maxillary injection technique. In addition, the physiological
role of the nociceptor membrane channels will be analyzed
in terms of the effect of warming the anesthetic on reducing
the perception of pain.
Patients and methods
Study design and sampling
A double-blind, split-mouth randomized clinical trial was
conducted according to Consolidated Standards of Reporting
Trials (CONSORT) guidelines and was reviewed and approved
by the Ethics and Research Committee of the Valdivia Health
Service, Government of Chile (no. 075/2015). The study is
registered under clinical study # ISRCTN78906795.
Students from the School of Dentistry at the Universidad
Austral de Chile, Valdivia, Chile participated. The students
selected had American Society of Anesthesiologists I health
status, were aged between 18 and 35 years, were of both gen-
ders, and had not undergone any treatment with nonsteroidal
anti-inflammatory drugs in the 2 months prior to the study
and were without dental pain or infection at the puncture site.
Before starting the study protocol, all participants provided
written informed consent approved by the ethical committee.
The sample size was based on a pilot study15 who showed
a mean difference of 18.5 points on the visual analog scale
(VAS) using local anesthetic at 42°C. Considering a 5% level
of significance, a study power of 90% and including 25% of
the sample in case of loss of observers, a total of 70 subjects
were estimated.
Temperature control of the anesthetic
cartridge
To warm the anesthesia, a researcher (CB) undertook a pilot
study with 20 cartridges of anesthesia. A baby bottle warmer
was used (Phillips Avent®, Amsterdam, the Netherlands)
similar to that used in previous reports.6,11,12 The cartridge of
anesthetic was left in a hermetically sealed plastic bag that
was placed in the warmer containing 300 mL of cold water
(21°C). Using the maximum power of the apparatus, the
anesthetic fluid reached 42°C (107.6°F) in 3 min 50 seconds.
Randomization and use of anesthetic
To determine the chronological order of injection with the
anesthesia warmed to 42°C, a simple randomization func-
tion of the program MS Excel 2013 (Microsoft Corpora-
tion, Redmond, WA, USA) was used. The first injection
was applied on the subject’s dominant side (left/right) and
the temperature used depended on the random number
(even=room temperature; odd=42°C) with the participant
blinded to it. For anesthetic infiltration to the anterosuperior
alveolar nerve, a researcher (CT) with more than 10 years of
experience in dental anesthetic techniques administered the
anesthetic according to the steps and technique described by
Malamed.4 The injection point was placed in the mucobuc-
cal fold apically between teeth #6 and #11 using a 30G short
needle ( Septoject XL; Septodont, Saint-Maur-des-Fossés,
France) and injecting 0.9 mL of the anesthetic (Alpha-
caine100®; Nova DFL, Taquara Rio de Janeiro, Brazil) at
a speed of 0.15 mL/second.16 Immediately after the injec-
tion, a second researcher presented the patient with a 100
mm VAS (0=absence of pain; 100=unbearable pain) asking
“How much pain did you feel as the anesthesia was being
administered?”. The pain indicated with a finger or verbally
was recorded. There was a 1-week washout period after the
first injection and the second injection was administered on
the contralateral side of the maxilla with the other anesthetic
temperature according to the described random sequence.
Data analysis
The temperature used (42°C and room temperature) was the
independent variable and the dependent variable was the
level of pain perceived during the anesthetic injection. To
verify the effectiveness of warming the anesthetic to 42°C
vs. room temperature (21°C), the parametric behavior of the
pain records in both study groups was analyzed by a third
blinded researcher (PCA) using the Shapiro–Wilk test. Then,
the median, SD (±) and 95% CIs of the VAS of all the subjects
in both study groups were compared using the corresponding
test according to the distribution of the values (Student’s t-test
or Wilcoxon test; p<0.05) using STATA v10.0 (StataCorp LP,
College Station, TX, USA).
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Effect of warming anesthesia in pain perception
Results
In total, 83 volunteer students participated between July
and September 2015. Based on the criteria for selection and
after the 1-week washout period, 11 students were excluded
(Figure 1). Finally, 72 subjects (51 men) were analyzed, who
had an average age of 22.1±2.45 years (range 18–29 years;
men: 21.9±2.3 years, women: 22.3±2.6 years).
The distribution of normality of the pain records in the
two groups was found to be nonparametric (p=0.001). The
level of pain perceived according to the VAS by the 42°C
group was significantly lesser that that of the room tempera-
ture group (p<0.001; Table 1).
Discussion
According to the hypothesis raised here, it was verified that
the use of anesthesia at 42°C significantly reduced pain
compared to that at room temperature during the injection
of local anesthesia using the maxillary infiltration technique.
Our results are consistent with previous reports on the
effect of warming the anesthesia on the perception of the
pain in the trigeminal territory: using 2% procaine 1:80,000
epinephrine (Palex Medical Laboratories, Madrid, Spain) at
43°C in plastic surgery;6 1% lidocaine 1:200,000 epineph-
rine (Astra Laboratories, Cambridge, UK) at 38°C in cheek
or face anesthesia17 and 2% lidocaine (Astra Laboratories)
with 5 mL 0.5% bupivacaine at 37°C in cataract surgery.18 In
dentistry, special attention is paid to this issue, considering
that most dental procedures require local anesthesia. Rogers
et al9 showed that the use of anesthesia at body temperature
was more comfortable than at room temperature. Neverthe-
less, other reports10,11 have not demonstrated a positive effect
and their methodology does not permit comparison with
our results, mainly due to the lack of data on the method of
warming of the anesthetic and to the use of scales for facial
expression, movements of extremities or perceived crying.11
On the other hand, there are studies that even suggest not
warming the anesthetic cartridges because the drug and the
vasoconstrictor inside could degrade, which would decrease
its effectiveness.4,19 Although the manufacturer’s instructions
encourage keeping the cartridges at room temperature, there
are reports that show that lidocaine can tolerate repeated
sterilization by autoclave20 and that epinephrine can withstand
repeated warming with no appreciable degradation,21 even at
extreme temperatures of up to 51.7°C for an accumulated time
of 13.25 hours.22 However, this information is inconclusive
in dentistry given the paucity of technical reports based on
electronic data that can verify the preservation of anesthetic
compounds inside the cartridge at different temperatures.
Figure 1 CONSORT ow diagram.
Note: The subjects participated in both study groups (split mouth) with a 1-week washout.
Abbreviation: CONSORT, Consolidated Standards of Reporting Trials.
Anesthesia 42ºC
Assessed for eligibility (n=93)
Randomized (n=87)
Excluded (n=6)
Not meeting inclusion criteria (n=5)
Declined to participate (n=1)
Anesthesia room temperature
Allocated to intervention (n=87)
Lost to follow-up (n=5) Lost to follow-up (n=5)
Discontinued intervention (did not return n=5)
Analyzed (n=72) Analyzed (n=72)
AnalysisFollow-up Allocation Enrollment
Received allocated intervention (n=87)
Allocated to intervention (n=87)
Received all allocated intervention (n=87)
Discontinued intervention (did not return n=5)
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Aravena et al
Role of temperature on the effect of
anesthesia in Transient Receptor Potential
Vanilloid-1 (TRPV1) channels
The role of local anesthetics is to prevent a change in the
propagation of the nerve impulse along the nociceptor by
blocking sodium channels. The liposoluble nature of lido-
caine is a result of an aromatic ring and the tertiary form of
the terminal amine;23 this that it spreads freely through the
plasma membrane, reaching the intracellular fluid where it
can perform its function. It can be inferred from the collected
data that warming the anesthesia to 42°C may aid the mol-
ecule in penetrating the nociceptor, thereby contributing to a
faster blocking of the sodium channels, impeding propagation
of the pain signal. This phenomenon could be explained by
two possible mechanisms: first, an increase in the fluidity of
the lipid membrane, which may allow lidocaine to cross the
membrane more easily, reaching the effective concentration
to produce analgesia more quickly and the second mecha-
nism may be related to the presence of TRPV1 channels24
expressed densely in the trigeminal tissue.25
TRPV1 is the founding member of a subfamily of heat-
sensitive TRP channels that allow primary afferent nociceptors
and other cell types to detect changes in the environment.26
Initially called capsaicin receptor (VR1), TRPV1 is not only
activated in the presence of vanilloid compounds, such as the
active compound in chili pepper, but also in the temperature
range that is close to harmful, over 42°C.24 Thus, TRPV1 acts
as a polymodal integrator of chemical and thermal signals,
modulating the excitability of the nociceptor to changes in the
local tissue environment.25 Once the TRPV1 has been acti-
vated, the pore is wide enough to permeate the large cations.
When more than one factor activates the channel, a synergic
action is exerted that causes a strong activation of TRPV1,
which increases the permeabilization of the large cations.26–28
Limitations
The limitations of our study are related to patient–dentist
variables. It must be considered that the subjects were healthy
volunteers who do not necessarily represent the population
that requires local anesthesia. In addition, the description of
the subjective variable as pain using a VAS is dependent on
the emotional state and previous history of the subjects to the
perception of pain and the injection of anesthetics. However,
this is recognized as a valid and reliable method in clinical
use.29 The control of the speed and anesthetic technique var-
ies according to the dentist’s experience, the reason for the
anesthesia and the anatomy of the puncture site, a situation
which generates different levels of pain perception condi-
tioned mainly by the patient’s previous experience with dental
treatment.13,14 In any case, it is advisable to inject the anes-
thetic slowly4,16 since it has been proven that the sensitivity
of the nociceptors not only depends on the type of chemical
agent but also on the mechanical effects of the injection site
and the speed and volume of the injection.2 Despite these
limitations, we have controlled the possible risks of bias
set out by Hogan et al,12 such as adequate generation of
the intervention sequence, masking of the participants and
analysis of results.
Conclusion
In conclusion, warming the anesthetic cartridges to 42°C
demonstrated a reduction in pain during the injection of
anesthesia in the maxillary infiltration technique compared to
the anesthesia used at room temperature. These results con-
tribute to the need to use an easy and replicable method that
can control pain during dental injection, so as to reduce pain
and anxiety levels during dental treatment using domestic
portable equipment such as incubators with a thermostat or
baby bottle warmer. It is suggested that there should be future
analyses of patients with pulpal pathologies and discussion
based on the physiological and pharmacologic foundations
that can explain this clinical result.
Disclosure
The authors report no conflicts of interest in this work.
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Table 1 Level of pain perceived by the study group according to the visual analog scale of pain
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Room
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analgesics. The journal is included in PubMed, and welcomes submitted
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