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Clinical Journal of Pharmacology and Pharmacotherapeutics
2019 | Volume 1 | Article 1006
026
© 2019 - Medtext Publications. All Rights Reserved.
The Efcacy of Preemptive Analgesia Using a Non-Opioid
Alternative Therapy Regimen on Postoperative Analgesia
Following Block Bone Graft Surgery of the Mandible: A
Prospective Pilot Study in Pain Management in Response to
the Opioid Epidemic
Research Article
Cameron Y.S. Lee, DMD, MD, PHD, MPH1*, and Jon B. Suzuki, DDS, PHD, MBA2
1Private Practice in Oral, Maxillofacial and Reconstructive Surgery, Aiea, Hawaii 96701; Clinical Professor of Periodontology and Oral Implantology; Kornberg
School of Dentistry, Temple University, Philadelphia, PA 19140, USA
2Professor (Emeritus) of Microbiology and Immunology (School of Medicine); Professor (Emeritus) of Periodontology and Oral Implantology (School of Dentistry);
Kornberg School of Dentistry, Temple University, Philadelphia, PA 19140, USA
Citation: Lee CYS, Suzuki JB. The Efcacy of Preemptive Analgesia
Using a Non-Opioid Alternative Therapy Regimen on Postoperative
Analgesia Following Block Bone Graft Surgery of the Mandible: A
Prospective Pilot Study in Pain Management in Response to the Opioid
Epidemic. Clin J Pharmacol Pharmacother. 2019; 1(2): 1006.
Copyright: © 2019 Cameron Y.S. Lee
Publisher Name: Medtext Publications LLC
Manuscript compiled: Feb 13th, 2019
*Corresponding author: Cameron Y.S. Lee, DMD, MD, PHD,
MPH, Oral, Maxillofacial and Reconstructive Surgery, Department
of Periodontology/Oral Implantology, Kornberg School of Dentistry.
Temple University, 98-1247 Kaahumanu Street. Suite 314. Aiea, Hawaii
96701, USA, Tel: 808-484-2288; E-mail: CLee555294@aol.com
Abstract
Purpose: e authors examined whether a novel alternative treatment regimen that is opioid-free administered preemptively 3 days prior to block bone gra
surgery of the mandible has a preemptive analgesic eect on the intensity of pain at the gra harvest site during the 72-hour postoperative period.
Materials and methods: is qualitative prospective pilot study was conducted in a single oce in 2018. irty-four patients were randomly divided into two
groups: Group A (14 patients) were provided the opioid-free regimen three days prior to surgery; Group B (20 patients) were not provided the opioid-free
regimen, but only opioid analgesics. e primary outcome variable was pain intensity measured at the bone gra harvest site by each patient using a 10-point pain
intensity scale (PIS) from 0 (no pain) to 10 (worst pain possible). Secondary outcome variables measured were the total number of opioid rescue analgesics used
over a 72-hour postoperative period and the time interval to initial use of opioid analgesics to relieve the postoperative pain in both cohort groups. A P value less
than .05 was statistically signicant.
Results: Patients in Group A recorded lower pain intensity scores at all time intervals. e median time interval to use of the rst opioid rescue analgesic aer
surgery in Group A was 4.3-hours compared with 1.9 hours for patients in Group B. e average postoperative pain intensity score for Group A patients was
5.6 on the 0 to 10 PIS. e average number of opioid rescue analgesics consumed was 2.3 tablets per day over the 72-hour postoperative period. For Group B
patients, the average postoperative pain intensity score was 7.1 on the PIS and average number of opioid analgesics used was 3.8 tablets per day over the 72-hour
postoperative period.
Conclusions: e results of the study illustrate that postoperative pain intensity was lower in the group of patients with the opioid-free regimen when used
preemptively compared to the group of patients that did not receive the opioid-free regimen. Further, use of this novel treatment alternative in managing
postoperative pain resulted in less consumption of opioid analgesic medication and increased the time interval to rst use of an opioid analgesic. e results of
this pilot study support the need for novel alternative and complementary analgesic strategies.
Introduction
e opioid abuse, addiction, and overdose epidemic in the
United States is at a public health crisis and has caught the attention
of the Food and Drug Administration (FDA), National Institute of
Drug Abuse (NIDA), National Institutes of Health (NIH), Drug
Enforcement Agency (DEA), the Centers for Disease Control (CDC),
and medical and dental organizations such as the American Medical
Association (AMA), American Dental Association (ADA), and the
American Association of Oral and Maxillofacial Surgeons (AAOMS)
[1-5]. On October 26, 2017, President Donald Trump declared the
opioid crisis a national public health emergency under the federal
Public Health Services Act [6].
Opioid analgesics (synthetic variants of opium) have always been
important in the management of acute and chronic pain. But when
used by patients improperly the consequences can be unforgiving.
Aer marijuana, prescription painkillers are the second most abused
© 2019 - Medtext Publications. All Rights Reserved. 027
Clinical Journal of Pharmacology and Pharmacotherapeutics
2019 | Volume 1 | Article 1006
drug [7]. In 2016, greater than 11 million Americans misused
opioid drug prescriptions. Since 1994, deaths from opioid use more
than quadrupled and parallels the increased number of opioid
prescriptions [8-10]. In 2015, there were over 33,00 deaths reported
involving opioids.10 Further, over 2 million citizens are addicted to
opioids, In 2015, greater than 12 million reported misusing opioids.11
Such increased morbidity and mortality can also be attributed to
injudicious prescribing and has increased the spread of HIV and
hepatitis C infections and heroin use [11,12].
While in oce, former President Barrack Obama and his
administration did address the opioid epidemic as millions of dollars
were invested in drug treatment and monitoring programs. As part of
this call to action, the Centers for Disease Control developed guidelines
for clinicians in the prescribing of opioids [13]. However, the opioid
epidemic cannot be solved completely by our federal government.
Clinicians must also be held accountable [14]. In the American
Association of Oral and Maxillofacial Surgeons White Paper on
opioid prescribing for acute and postsurgical management, clinicians
should decrease the number of opioid drug prescriptions to control
the post-operative pain to reduce opioid misuse and abuse [15]. Most
important, clinicians can elect to prescribe non-opioid medications
as a safer alternative to opioid drugs to manage postsurgical pain and
avoid prescribing long-acting and extended release opioids.
Preemptive analgesia has received considerable attention in the
past few years. e goal of preemptive analgesia is to control and
decrease postsurgical pain when it is most intense prior to exposing
the patient to the surgical procedure [15]. is will reduce the reliance
of opioid analgesics to control the postoperative pain, lead to a faster
return to daily life activities and reduce the cost of overall patient
care [16,17]. Several clinical trials established that direct links with
preemptive analgesia decreases postsurgical pain resulting in less
dependence on pain medication and increased patient comfort and
satisfaction [18-23]. Acute pain is due to an inammatory cascade that
occurs in the tissues and results in chemical, mechanical and thermal
nociceptive stimuli from the surgical procedure [18,24]. Preemptive
analgesia attempts to inhibit nociceptive signals from peripheral and
central pain pathways that prevents release of chemical mediators,
such as histamine, substance P, bradykinin and prostaglandins that
results in primary hyperalgesia at the site of tissue injury and may last
for several hours aer tissue injury [15,18,25]. Hyperalgesia during
surgery in the oral cavity is due to peripheral sensitization of periosteal
and mucosal receptors from large amounts of prostaglandin release
that appears one hour aer the surgical procedure. is facilitates
peripheral and central sensitization before tissue trauma and injury
from the surgical procedure [26-28]. A reduction in sensitization
is believed to reduce postsurgical hyperalgesia, allodynia and the
magnitude and duration of postsurgical pain that could inuence the
need for rescue analgesics, post-surgically [18,25,27].
Although controversial regarding its eectiveness in controlling
postsurgical pain, preemptive analgesia has been studied in the surgical
removal of impacted third molars with dierent pharmacologic agents
because of the moderate to severe patient response to pain that occurs
6 to 8 hours, postsurgery [16,17,19-21,23]. However, the severity of
postsurgical pain aer harvesting monocortical blocks of bone from
the posterior mandible and ramus in preparation for placement of
dental implants in the jaws has not b een studied. e painful stimuli of
so tissues due to periosteal and muscle dissection and ultimately, the
osteotomy to harvest the block of bone from the posterior mandible
will cause moderate to severe postoperative pain and swelling.
Interestingly, current research with opioids in preemptive
analgesia has revealed minimal clinical ecacy in controlling
postsurgical pain [25,28]. Because of the opioid epidemic, the authors
evaluated a novel opioid-free alternative treatment regimen during
the preemptive analgesic stage to control postoperative pain at the
bone gra harvest site at the ascending ramus and posterior mandible
in preparation for dental implant surgery. Like removal of impacted
mandibular third molar teeth and orthognathic surgery that requires
advanced surgical skill and can be challenging even for experienced
surgeons, the postoperative recovery observed in the maxillofacial
region from harvesting bone from the mandible is associated with an
acute inammatory response that includes pain, bleeding, so tissue
edema and ecchymosis [29,30]. For the surgical patient who completes
any of these surgical procedures, the rst 24 hours aer surgery
are considered the most excruciating. As an anesthesia strategy,
preemptive analgesia may decrease the pain intensity associated with
block bone gra surgery and decrease the number of opioid analgesics
during the postoperative recovery period.
e VEGA Oral Care Recovery Kit evaluated in this study
is opioid-free and has been shown to accelerate wound healing,
decrease pain, edema and ecchymosis [31]. It consist of 16 active
ingredients that are monographed in the Homeopathic Pharmacopeia
of United States (HPUS) and recognized for their accelerated healing
properties. However, there are no published articles in the peer-
reviewed medical and dental literature as a preemptive analgesic for
controlling postoperative pain. e hypothesis of this study is that
preemptively managing pain before its onset with this non-opioid
alternative regimen may eectively reduce the pain intensity and
number of opioid rescue analgesics consumed in the postoperative
period. Specic goals of this study are to evaluate if the VEGA Oral
Care Recovery Kit administered 3 days prior to block bone gra
surgery of the mandible would produce a preemptive analgesic eect
compared with no treatment with patients who underwent harvesting
of monocortical blocks of bone from the posterior mandible and
ramus with local anesthesia. e primary outcome variable is pain
intensity measured at the bone gra harvest site. Secondary outcome
variables measured are the total number of opioid rescue analgesics
used over the 72-hour postoperative period and the time interval to
use of the rst opioid rescue analgesic.
Materials and Methods
Study Design and Participants
is prospective qualitative pilot study was conducted on a
group of 34 patients in a single oce (CYSL) in 2018. Demographic
characteristics for both groups are summarized in Table 1. Gender
was measured as a binary variable, while race was measured as a
categorical variable. e primary outcome variable was pain intensity
measured at the bone gra harvest site using a 10-point pain intensity
scale (PIS) from 0 (no pain) to 10 (worst pain possible). Secondary
outcome variables measured are the total number of rescue opioid
analgesics used over a 72-hour postoperative period (Table 2 and 3)
and the time interval to initial use of an opioid rescue analgesic (Table
4). A P value less than .05 was statistically signicant.
Patients included in the study were over 18 years of age and
diagnosed with either atrophy in the vertical or horizontal dimension
of the maxilla or mandible and referred for bone gra reconstructive
surgery in preparation for dental implant surgery. All patients were
© 2019 - Medtext Publications. All Rights Reserved. 028
Clinical Journal of Pharmacology and Pharmacotherapeutics
2019 | Volume 1 | Article 1006
identied as either physical status class I or II according to the
American Society of Anesthesiologists for this elective surgical
procedure in an oce-based setting under local anesthesia. Excluded
from this study were patients with a history of opioid or alcohol
misuse, recreational drug abuse, chronic pain and past medical
history of treatment for chronic pain. A total of 42 monocortical
blocks of bone were harvested from the twenty-nine patients from
the ramus and posterior mandible as described by Pikos [32]. Every
patient included in this study was informed of the primary diagnosis,
treatment options, surgical procedure and goals of this prospective
pilot study. Written and verbal informed consent from each patient
and ethical approval was obtained prior to initiation of this study.
Patients were randomly divided into 2 groups. Group A patients
(14 in preemptive treatment group) received the opioid-free regimen
prior to surgery and the instructions on it use. In addition, each
patient was prescribed ve tablets of an opioid rescue analgesic (5mg
hydrocodone/325mg acetaminophen). Group B patients (20 in cont rol
group) only received a prescription of opioid analgesic (total of 15),
5mg hydrocodone/acetaminophen 325mg aer the surgery to control
the postsurgical pain. All patients were prescribed chlorhexidine
gluconate 0.12% mouthwash that was to be used twice per day for a
period of seven days.
Study Protocol
All 34 patients completed bone gra surgery under local
anesthesia with vasoconstrictor. To harvest the monocortical block
gras, local anesthetic consisting of 2% lidocaine with 1:100,000
epinephrine was administered for nerve block of the inferior alveolar
nerve and buccal so tissue inltration at the bone gra harvest site.
e average dose used at the bone gra harvest site was 7.2 ml. At the
recipient bone gra site, the average dose of local anesthesia was 5.4
ml. e operation time was recorded from initial mucosal incision to
placement of the last suture.
Monocortical blocks of bone harvested from the buccal posterior
and ascending ramus of the mandible were used to increase the
vertical and horizontal dimensions of the future implant sites (Figure
1-3). Bone gra average size harvested from the mandible was width
3-4mm; length 10-20mm and height 8-12mm. Of the 14 patients in
Group A, ve patients had two monocortical blocks of bone harvested
from the bilateral posterior mandible to reconstruct implant sites in
the anterior maxilla. Eight patients in Group B had two monocortical
blocks of bone harvested from the bilateral posterior mandible to
reconstruct the anterior or posterior maxilla in preparation for future
implant surgery.
Study Variables
Primary Outcome Variable: To evaluate postoperative pain,
immediately aer the completion of the surgical procedure all
patients began to complete the pain scale as instructed. Patients were
instructed on how to complete the 10-point pain intensity scale (PIS)
regarding postoperative pain intensity that recorded pain from 0 (no
pain) to 10 (worst pain experienced). e primary outcome variable
is the postoperative pain intensity recorded from the results of the
intensity scale (PIS). All participants were instructed to record their
pain intensity scores at 4, 8, 12, 16, 24-time intervals over the next 72
hours aer surgery. An assumption could be made that the recording
of low pain intensity scores correlates with an increased time interval
to use of opioid rescue analgesics and in a reduction in the amount of
rescue analgesic used. Such an assumption is based on the hypothesis
Group 1 (n=14) Group 2 (n=20)
Female 13 16
Male 1 4
Ethnicity
asian 13 17
white 2
other 1 1
ASA Classication
1 2 4
2 12 16
3
Table1: Patient Demographics.
Group 1: VEGA Oral Care Kit
Group 2: Control Group
POD 1 POD 2 POD 3
Average Postoperative Pain Intensity 6.3 5.5 5
*Average Number of Opioids 3.5 2 1.5
POD: Postoperative Day
*Average number of opioids used per 24 hours
Table 2: Group 1 Opioid Rescue Analgesics Consumed over 72 Hours.
POD 1 POD 2 POD 3
Average Postoperative Pain Intensity 8.5 7.5 5.5
*Average Number of Opioids 5.5 4 2.5
*Average number of opioids used Per 24 hours.
Table 3: Group 2 Average Opioid Consumption Over 72 Hours.
Group 1 Group 2
Time Interval (hr) 4.3 1.9
Table 4: Time Interval to Use of First Opioid Analgesic.
Group 1: VEGA Oral Care Kit
Group 2: Control Group
Figure 1: Clinical photograph of 42-year old Asian female missing two
anterior maxillary incisor teeth causing psychological embarrassment and
anxiety.
Figure 2: Two monocortical blocks of bone harvested from bilateral posterior
ascending ramus of mandible four months ago rigidly xated to maxilla
using micro screws now successfully incorporated with maxilla and ready for
implant placement. Post-operative pain is most intense at harvest site during
rst 24-48 hours after surgery.
© 2019 - Medtext Publications. All Rights Reserved. 029
Clinical Journal of Pharmacology and Pharmacotherapeutics
2019 | Volume 1 | Article 1006
that the opioid -free alternative regiment has a preemptive analgesic
eect.
Secondary Outcome Variable: Secondary outcome variables
evaluated were the total amount of opioid rescue analgesics consumed
to relieve the postoperative pain over the 72-hour observation period
and the time interval to administration of the rst opioid rescue
analgesic. Time interval is the time from the end of the surgical
procedure to use of the opioid rescue analgesic.
Statistical Analysis
Data collected from this pilot study was entered into a statistical
database and conducted using the Statistical Package for Social
Sciences (SPSS for Windows, version 25; SPSS, Chicago, IL). e level
of signicance for all statistical evaluations was set at P < .05. Data
are presented as a mean +/- standard deviation. Descriptive statistics
were used to describe the data obtained for each clinical outcome.
Unpaired student t test with a 95% condence interval was used to
compare mean postoperative pain intensity scores and use of rescue
opioid analgesics. e Wilcoxon rank sum test was used to evaluate
the time interval to use of opioid analgesics for both groups.
Results
A total of 40 adult patients were initially enrolled in the project.
However, only 34 completed this study as 6 patients were removed f rom
the research group due to lack of instructional compliance. Patients in
Group A (14 in preemptive treatment) reported lower cumulative pain
intensity scores throughout the 72-hour postoperative observation
period compared to patients in Group B (20 in control group) (Table
2 and 3). e average postoperative pain intensity score for patients in
Group A using the PIS was 5.6 over the 72-hour observational period
(range 2 to 8.5). e average rescue opioid analgesic consumption
over the 72-hour observational period was 2.3 tablets per day. For
patients in Group B, the average postoperative pain intensity score
was 7.1 (range 4.0 to 9.5) on the PIS. e average number of opioid
analgesics consumed to relieve postoperative pain over the 72-hour
observational period was 3.8 tablets per day. e median time interval
to use of the rst opioid rescue analgesic was 4.3 hours for patients in
Group A. For patients in Group B, the median time interval to initial
use of opioid pain medication was 1.9 hours.
Discussion
e intensity of postoperative pain is directly correlated with
the type of surgical procedure the patient completes. Harvesting
monocortical blocks of bone is similar to orthopedic and orthognathic
surgery. All three types of surgical procedures commonly involve
sharp dissection of the periosteum and muscles and surgical
osteotomies with a high-speed cutting device such as a saw or ssure
bur that result in moderate to severe postoperative pain and the need
for opioid analgesics to control the pain. In surgery, strategies utilizing
medications have been developed to decrease the postoperative
pain response, including the use of opioids [25,28,33-40]. Opioid
analgesics such as hydrocodone and oxycodone are commonly
prescribed to reduce postoperative pain with or without non-steroidal
anti-inammatory drugs (NSAIDS) to provide pain relief. e dental
profession is the third highest prescribers of opioid analgesics in the
United States [41]. In a study by Denisco and colleagues [42] greater
than 3 million patients each month are exposed to opioid analgesics
from oral and maxillofacial surgeons. Opioids provide excellent
pain relief, but are associated with drug tolerance, abuse and risk of
addiction. is is the driving force for the search for an ecacious
opioid-free alternative treatment regimen in the management of
postoperative pain [43].
In a third molar study by Ong evaluating the ecacy of ketorolac
on postoperative pain, the cohort of patients receiving the pain
medication prior to surgery reported signicantly lower levels of pain
12 hours post-surgery compared to the cohort who received ketorolac
aer surgery. In another study by Ong on rofecoxib, the group of
patients who received the medication prior to surgery also reported
decreased levels of pain over the rst 12 hours post-surgery, compared
to the group of patients who received rofecoxib aer surgery. Studies
by Presser-Lima and Fontanella and Zor also showed that preemptive
analgesia administered to their patients resulted in less pain
postoperatively. However, some studies failed to show the benets of
preemptive analgesia in the post-surgical, but rather a reduction in
the amount of rescue drug used to control the postoperative pain, or
in a delay in the time for the onset of pain experienced by the patient.
Although the mechanism of action is not entirely known, a reduction
or delay in the use of an opioid rescue analgesic may be due to the
preemptive eect of the alternative therapy in our study. Stimulation
of free nerve endings at the bone harvest site causes nociceptive pain.
As the VEGA Oral Care Recovery Kit is provided as an oral
rinse, sublingual spray and topical gel, we hypothesize that all three
Figure 3: (A) Clinical photograph of patient without teeth. (B and C)
Intraoral view of anterior maxilla restored with implants and zirconia teeth.
© 2019 - Medtext Publications. All Rights Reserved. 030
Clinical Journal of Pharmacology and Pharmacotherapeutics
2019 | Volume 1 | Article 1006
routes of product administration contribute to the preemptive eects
due to peripheral and possibly, central sensitization by blockade of
nociception when applied three days prior to the date of the surgical
procedure and during the 72-hour postoperative period. e cohort
group that used the opioid-free regimen preemptively experienced
less postoperative pain (average pain intensity of 5.6 over the 72-hour
observation period) than the control group based on the results of
the pain intensity scale (average pain intensity of 7.1 over 72 hours,
postoperatively). is observation was most signicant at the 2 to
4-hour time interval aer surgery when the reported pain was most
severe for patients who were not treated preemptively. When used
preemptively, onset of postoperative pain by a mean time of 4.3 hours
before having to resort to use of any opioid rescue analgesic was
observed. Such a preemptive analgesic aect may be due to inhibition
of peripheral nociceptor input. For the surgical patient, a prolonged
pain-free period from the end of surgery to the rst use of an opioid
analgesic to control the onset of postoperative pain is clinically
signicant. Like third molar surgery where the postoperative pain
is most intense 2 to 4 hours aer surgery, it has been the authors
experience that the postoperative pain from harvesting monocortical
blocks of bone at the osteotomy site is also most intense during this
time interval.
is pilot study did have limitations, such as not being blinded
and its small sample size. Studies that are not blinded can result in
research bias, as both the research investigators and the patient know
which treatment they were assigned to. As the study included only 34
patients, its small sample size may aect statistical power. As clinicians
are well-aware of, postoperative pain is subjective, dicult to measure
and perceived dierently among dierent age groups, races and
cultures. Such self-reporting by patients is another limitation of any
study and could be inuenced by several dierent factors. In both
groups, over 90% of the patients in this qualitative study were Asian,
female and older in age. Many of the participants in both groups
limited their opioid consumption to control the postoperative pain.
With advanced age, there may be a “blunting eect” on peripheral
nociceptive function that decreases pain perception and the need for
less analgesic medication [44,45].
Conclusion
is novel, opioid-free alternative form of therapy administered
preemptively prior to block bone gra surgery resulted in decreased
postoperative pain, less reliance of opioid analgesics and increased
the time interval to use of an opioid analgesic. e authors believe
that there is a denite role in the use of this novel opioid-free
alternative therapy in managing postoperative pain. As the opioid-
abuse epidemic is now at a national public health crisis with no end in
sight, the use of a non-opioid product should be considered by every
clinician who manages postoperative pain in their daily practice.
Because of the paucity of studies in this area of pain management,
long-term randomized clinical studies are needed as alternative
and complementary treatment regimens do have a role in pain
management in oral and maxillofacial surgery and implant dentistry.
References
1. Cali RM, Woodcock J, Ostro S. A Proactive Response to Prescription Opioid
Abuse. N Engl J Med. 2016;374(15):1480-5.
2. Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic
pain- United States, 2016. JAMA. 2016;65(1):1624-45.
3. Centers for Disease Control and Prevention. Opioid overdose: understanding the
epidemic. August 30, 2017.
4. ADA announces new policy to combat opioid epidemic. American Dental
Association News (03/26/18).
5. Opioid prescribing: acute and postoperative pain management. American Association
of Oral and Maxillofacial Surgeons White Paper.
6. Rutkow L, Vernick JS. Emergency Legal Authority and the Opioid Crisis. N Engl J
Med. 2017;377(26):2512-2514.
7. Okie S. A ood of opioids, a rising tide of deaths. N Engl J Med. 2010;363(21):1981-5.
8. Paulozzi L, Jones C, Mack K. Vital signs: overdoses of prescription opioid pain
relievers- United States, 1999-2008. MMWR;2011:60(43):1487-92.
9. Rudd RA, Aleshire N, Zibbell JE, Gladden RM. Increases in Drug and Opioid
Overdose Deaths--United States, 2000-2014. MMWR Morb Mortal Wkly Rep.
2016;64(50-51):1378-82.
10. National Institute on Drug Abuse, National Institutes of Health. Overdose death
rates.
11. Prescription drug use and misuse in the United States: results from the 2015 National
Survey on Drug Use and Health.
12. Comerci G Jr, Katzman J, Duhigg D. Controlling the Swing of the Opioid Pendulum.
N Engl J Med. 2018;378(8):691-3.
13. Compton WM, Jones CM, Baldwin GT. Relationship between nonmedical and
prescription-opioid use and heroin use. N Engl J Med, 2016;374:154-63.
14. Murthy VH. Ending the Opioid Epidemic - A Call to Action. N Engl J Med.
2016;375(25):2413-2415.
15. Gottschalk A, Smith DS. New concepts in acute pain therapy: preemptive analgesia.
Am Fam Physician. 2001;63(10):1979-84.
16. Costa FW, Esses DF, de Barros Silva PG, Carvalho FS, Sá CD, Albuquerque AF,
et al. Does the preemptive use of oral nonsteroidal anti-inammatory drugs
reduce postoperative pain in surgical removal of third molars? A meta-analysis of
randomized clinical trials. Anesth Prog. 2015;62(2):57-63.
17. Alcântara CE, Falci SG, Oliveira-Ferreira F, Santos CR, Pinheiro ML. Pre-emptive
eect of dexamethasone and methylprednisolone on pain, swelling, and trismus aer
third molar surgery: a split mouth randomized triple-blind clinical trial. Int J Oral
Maxillofac Surg. 2014;43(1):93-8.
18. Ong CK, Lirk P, Seymour RA, Jenkins BJ. e ecacy of preemptive analgesia for acute
postoperative pain management: a meta-analysis. Anesth Analg. 2005;100(3):757-73.
19. Gutta R, Koebn CR, James LE. Does ketorolac have a preemptive analgesic eect? A
randomized, double-blind, control study. J Oral Maxillofac Surg. 2013;71(12):2029-
34.
20. Bauer HC, Duarte FL, Horliana AC, Tortamano IP, Perez FE, Simone JL, et al.
Assessment of preemptive analgesia with ibuprofen coadministered or not with
dexamethasone in third molar surgery: a randomized double-blind controlled clinical
trial. Oral Maxillofac Surg. 2013;17(3):165-71.
21. Moore PA, Brar P, Smiga ER, Costello BJ. Preemptive rofecoxib and dexamethasone
for prevention of pain and trismus following third molar surgery. Oral Surg Oral Med
Oral Pathol Oral Radiol Endod . 2005;99(2):E1-7.
22. Kim JH, Seo MY, Hong SD, Lee J, Chung SK, Kim HY, et al. e ecacy of preemptive
analgesia with pregabalin in septoplasty. Clin Exp Otorhinolaryngol. 2014;7(2):102-5.
23. Mojsa IM, Stypulkowska J, Novak P, Lipczynski K, Szczeklik K, Zaleska M. Pre-
emptive analgesic eect of lornoxicam in mandibular third molar surgery: a
prospective, randomized, double-blind clinical trial. Int J Oral Maxillofac Surg.
2017;46(5):614-20.
24. Pogatzki-Zahn EM, Zahn PK. From preemptive to preventive analgesia. Curr Opin
Anaesthesiol. 2006;19(5):551-5.
25. Kissin I. Preemptive analgesia. Anesthesiology. 2000;93(4):1138-43.
26. Savage MG, Henry MA. Preoperative nonsteroidal anti-inammatory agents: review
of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;98(2):146-
53.
© 2019 - Medtext Publications. All Rights Reserved. 031
Clinical Journal of Pharmacology and Pharmacotherapeutics
2019 | Volume 1 | Article 1006
27. Woolf CJ, Chong MS. Preemptive analgesia- treating postoperative pain by preventing
the establishment of central sensitization. Anesth Analg. 1993;77(2):362-79.
28. Kelly DJ, Ahmed M, Brull SJ. Preemptive analgesia I: physiological pathways and
pharmacological modalities. Can J Anaesth. 2001;48(10):1000-10.
29. Savin J, Ogden GR. ird molar surgery- a preliminary report on aspects aecting
quality of life in the early postoperative period. Br J Oral Maxillofac Surg.
1997;35(4):246-53.
30. Bortoluzzi MC, Guollo A, Capella DL. Pain levels aer third molar surgical removal:
an evaluation of predictive variables. J Contemp Dental Prac. 2011;12(4):239-44.
31. VEGA Oral Care Recovery Kit. StellaLife. Glenview, IL, 2016.
32. Pikos M. Block autogras for localized ridge augmentation. Part II. e posterior
mandible. Implant Dent. 2000;9(1):67-73.
33. Dahl JB, Mřiniche S. Pre-emptive analgesia. Br Med Bull. 2004;71:13-27.
34. Lebrun T, Van Elstraete AC, Sandefo I, Polin B, Pierre-Louis L. Lack of a pre-emptive
eect of low-dose ketamine on postoperative pain following oral surgery. Can J
Anaesth. 2006;53(2):146-52.
35. Pozos-Guillen A, Martinez-Rider R, Aguirre-Banuelos P, Perez-Urizar J. Pre-emptive
analgesic eect of tramadol aer mandibular third molar extraction: a pilot study. J
Oral Maxillofac Surg. 2007;65(7):1315-20.
36. Ong KS, Seymour RA, Chen FG, Ho VC. Preoperative ketorolac has a preemptive
eect for postoperative third molar surgical pain. Int J Oral Maxillofac Surg.
2004;33(8):771-6.
37. Ong KS, Seymour RA, Yeo JF, Ho KH, Lirk P. e ecacy of preoperative versus
postoperative rofecoxib for preventing acute postoperative dental pain: a prospective
randomized crossover study using bilateral symmetrical oral surgery. Clin J Pain.
2005;21(6):536-42.
38. Presser Lima PV, Fontanella V. Analgesic ecacy of aceclofenac aer surgical
extraction of impacted lower third molars. Int J Oral Maxillofac Surg. 2006;35(6):518-
21.
39. Zor ZF, Isik B, Cetiner S. Ecacy of preemptive lornoxicam on postoperative
analgesia aer surgical removal of mandibular third molars. Oral Surg Oral Med Oral
Pathol Oral Radiol. 2014;117(1):27-31.
40. Becker DE. Pain management: Part 1: Managing acute and postoperative dental pain.
Anesth Prog. 2010;57(2):67-78.
41. Volkow ND, McLellan TA, Cotto JH, Karithanom M, Weiss SR. Characteristics of
opioid prescriptions in 2009. JAMA. 2011;305(13):1299-301.
42. Janssen SA, Arntz A. Anxiety and pain: attentional and endorphinergic inuences.
Pain. 1996;66(2-3):145-50.
43. Cigerim L, Eroglu CN. Comparison of clinical ecacies of preoperatively initiated
naproxen sodium-codeine phosphate in combination, diclofenac potassium, and
benzylamine hydrochloride for pain, edema, and trismus aer extraction of impacted
lower third molar: a randomized double-blind study. J Oral Maxillofac Surg.
2018;76(3):495-502.
44. Gagliese L, Gauthier LR, Macpherson AK, Jovellanos M, Chan VW. Correlates of
postoperative pain and intravenous patient-controlled analgesia use in younger and
older surgical patients. Pain Med. 2006;9(3):299-303.
45. De Cosmo G, Congedo E, Lai C, Primieri P, Dottarelli A, Aceto P. Preoperative
psychologic and demographic predictors of pain perception and tramadol
consumption using intravenous patient-controlled analgesia. Clin J Pain.
2008;24(5):399-406.
