2013 Toronto Academy of Dentistry, 76th Annual Winter Clinic New Approaches in Management of Endodontic Pain by Dr. Pavel S. Cherkas, Endodontist-Neuroscientist and Dr. Ruslan Dorfman, Molecular Geneticist

1. New Approaches in Management of
Endodontic Pain-- Making Sense of
Evidence, Technology and
Pharmacogenetics
Pavel S. Cherkas
DMD, PhD, MMedSc, MSc, BSc
Ruslan Dorfman
PhD, MBA, MSc, BSc
Faculty of Dentistry, University of
Toronto, Canada

2. Agenda for today’s course
• Anatomical structures in pain
signaling
• NSAIDs for analgesia
• Pain modalities
• Break - 10 min
• Antiepileptic drugs for pain control
• Acute pain as risk factor of chronic • Anesthesia – maximum results
pain
• Technologies for root canal
• Levels of evidence
treatment
• Pain as diagnostic tool
• Antibiotics in endodontic treatment
• Evidence based pain management • Statin-macrolide drug interactions
• Anthropologic risk factors of pain • Differences in NSAID response
• Pre-op pain – local anesthetics
• Use of steroids
• Opioids – when and what is
appropriate
• Outlook into future
• Conclusions

3. Do we know more today?
Can we treat better?

4. Peripheral innervation patterns cannot explain
pain referral

5. Acute vs. Chronic Dental Pain
Pain: An unpleasant sensory and emotional
experience associated with actual or
potential tissue damage or described in terms
of such damage (IASP)
Acute Pain: Transient, usually sharp, pain that
serves a protective function : warns the
organism of actual or impending tissue injury

6. Chronic Pain
Chronic Pain: Persistent, often dull or aching
pain, that continues long after an injury has
apparently healed (> 3 months duration);
serves no protective function and apparently
no biologic role
Some of most common pains occur in oro-facial
region, e.g. 10-15% prevalence of toothache or TMD

7. Uncontrolled acute pain increases the risk of
chronic pain
P(T)
60
12%
50
10%
40
8%
30
Series2
P(T)
6%
20
4%
10
2%
0
0%
1
2
3
4
5
6
7
8
9
10 11 12
1
2
3
4
5
6
7
8
9
10 11 12
P(T) = GB * Int[I(t)dt]
where P(T) is the probability of developing chronic condition by time T
Cherkas, 2013

8. Uncontrolled acute pain increases the risk of
chronic pain
P(T)
60
12%
50
10%
40
8%
30
Series2
20
P(T)
6%
4%
10
2%
0
0%
1
2
3
4
5
6
7
8
9
10 11 12
1
2
3
4
5
6
7
8
9 10 11 12
P(T) = GB * Int[I(t)dt]
where P(T) is the probability of developing chronic condition by time T
Cherkas, 2013

9. Pain control: what works and what does not?
•
•
•
•
•
Pre-op anesthesia – and NSAIDs
Local anesthesia
Post-op anesthesia – and NSAIDs vs opioids
Antibiotics
Steroids
Each treatment is associated with benefits and risks –
need to balance both

10. Levels of evidence
Systematic
Reviews
Evidence
Synthesis &
Guidelines
Critically Apprised
Individual Articles
Filtered
information
Randomized Controlled Trials
Case-control Studies & Case Series
and reports
Background information / Expert Opinion
Unfiltered
information

11. AAE Definitions of Pulpitis
Reversible pulpitis – A clinical diagnosis based
upon subjective and objective findings indicating
that the inflammation should resolve and the pulp
return to normal

12. AAE Definitions of Pulpitis
Irreversible pulpitis – A clinical diagnosis based on
subjective and objective findings indicating that the vital
inflamed pulp is incapable of healing
Additional descriptions:
Symptomatic – Lingering thermal pain, spontaneous pain,
referred pain
Asymptomatic – No clinical symptoms but inflammation
produced by caries, caries excavation, trauma, etc.
Take home message!

13. “Hot tooth”
• pulp diagnosed with irreversible pulpitis, with
spontaneous, moderate-to-severe pain
• patient who is sitting in the waiting room,
sipping on a large glass of ice water to help
control the pain

14. “Hot tooth”
• Chronic inflammation takes on an acute
exacerbation
• Influx of neutrophils
• Release of inflammatory mediators
• Release of proinflammatory neuropeptides
• Peripheral and central sensitization of nociceptors
• Increased neuronal excitability

15. Pain as a Diagnostic Tool
Barodontalgia
Affects air crew and aircraft passengers, underwater
divers
Pain or injury affecting teeth due to changes in
pressure gradients
Boyle’s Law: “at a given temperature, the volume of
a gas is inversely proportional to the ambient
pressure”
Robichaud & McNally, 2005

16. Pain as a Diagnostic Tool
Lack of knowledge concerning the type, characterization
and variety of fractures may lead to misunderstanding
with incorrect diagnosis and inappropriate treatment
•
•
•
•
•
Craze Lines
Split Tooth
Fractured Cusp
Vertical Root Fracture
Cracked Tooth

17. Craze Lines, Fractured and Split Teeth
Craze lines affect only the enamel, while fractured
cusps, cracked teeth and split teeth begin on the
occlusal surface and extend apically, affecting
enamel, dentin, and possibly, the pulp

18. Craze Lines, Fractured and Split Teeth
Craze lines affect only the enamel, while fractured cusps,
cracked teeth and split teeth begin on the occlusal surface
and extend apically, affecting enamel, dentin, and possibly,
the pulp
Craze lines
Fractured cusp
Take home message!
Cracked tooth

19. Case 1

20. Radiographic Examination

21. Radiographic Examination

22. Apical surgery and bone grafting

23. Apical surgery and bone grafting

24. Apical surgery and bone grafting

25. Apical surgery and bone grafting

26. Case 2 (Apical surgery)

27. Case 3 (Apical surgery)

28. Q: The teeth with irreversible pulpitis that are
the most difficult to anesthetize are:
1. the mandibular molars followed by mandibular
premolars, maxillary molars, and maxillary
premolars
2. the maxillary molars, and maxillary premolars,
mandibular molars followed by mandibular
premolars
3. the mandibular molars followed by maxillary
molars, mandibular premolars and maxillary
premolars
4. maxillary anterior teeth

29. Q: What anthropologic factors contribute to
response to opioid anesthesia ?
a. Age, Gender, Body weight
b.Race
c. Hair color
d.a+b
e.a+b+c

30. Q: Who has higher pain sensitivity, and
stronger response to opioid anesthesia?
A
B
C
D
E
F

31. Q: Who has higher pain sensitivity, and
stronger response to opioid anesthesia?
A
Red hair = 2 mutations in MC1R gene
melanocortin 1 receptor

32. Red-haired women are more sensitive to morphine
black vs yellow (e/e) MC1R mutant mice
MC1R gene function and morphine
(M6G) mediated inhibition of thermal
nociception in mice and electrical
current pain in humans.
Mogil J S et al. J Med Genet 2005;42:583-587
2 variants = red hair
Women are more sensitive
10 mg/kg morphine

33. Anesthetic efficacy of the inferior alveolar
nerve block in red-haired women
• Red hair and the MC1R gene were significantly
linked to higher levels of dental anxiety
• but were unrelated to success rates of the IAN
block in women with healthy pulps
Droll et al., 2012

34. Pre-Operative Pain Control
• Local anesthesia
Blocks (short and long-lasting)
Infiltration
Intraosseous
Intrapulpal

35. Intravenous cocaine increases plasma
epinephrine and norepinephrine in humans
• Epinephrine is contraindicated in patients who
have used cocaine within the last 24-48 hours
Take home message!
Sofuoglu et al., 2001

36. ABSOLUTE CONTRAINDICATIONS
Uncontrolled hyperthyroidism
The main reason for dentists to avoid local
anesthetic with vasoconstrictors in untreated
hyperthyroidism has been the possibility that
sympathomimetic amines could potentiate the
vascular effect of thyroid hormone.
Take home message!

37. ABSOLUTE CONTRAINDICATIONS
Pheocromocytoma
Pheocromocytoma is a rare but serious disorder
characterized by the presence of catecholamineproducing tumors.
The use of vasoconstrictors puts these patients
at high risk for lethal cardiac or cerebrovascular
complications and should be strictly avoided.
Perusse and Goulet, 1992
Take home message!

38. Success of the inferior alveolar nerve block in
patients with irreversible pulpitis
• Clinical studies in endodontics in patients with
irreversible pulpitis have found success with
the inferior alveolar nerve block occurred
between 15% and 57% of the time
Take home message!
Al Reader et al; 2011

39. Combination of preoperative ibuprofen/acetaminophen
and inferior alveolar nerve block in patients with
symptomatic irreversible pulpitis
• a combination dose of 800 mg ibuprofen and
1000 mg acetaminophen given 45 minutes
before administration of the IAN block did not
result in a statistically significant increase in
anesthetic success
Simpson et al., J Endod. 2011

40. Is a dose of 3.6 mL better than 1.8 mL for inferior alveolar nerve
blocks in patients with symptomatic irreversible pulpitis?
• For patients presenting with irreversible
pulpitis, success was not significantly different
between a 3.6-mL volume and a 1.8-mL
volume of 2% lidocaine with 1:100,000
epinephrine.
Fowler and Reader, J Endod., 2013
Take home message!

41. Why do we get anesthetic failures?
1. Anatomical variations
– central core theory
– Spread of the solution within the
pterygomandibular space
Hargraves 2002

42. Lip numbness
• Lip numbness can be obtained in 100% of the time
• Successful anesthesia in 15% -57% of the time
• The lack of lip numbness following IANB indicates
the injection was missed- no anesthesia
• Once lip numbness is achieved, lack of pulpal
anesthesia is not due to an inaccurate inferior
alveolar nerve block
Take home message!
Al Reader et al; 2011

43. Tachyphylaxis
2. Tachyphylaxis appears neither to be linked
to structural or pharmacological properties of
the local anesthetics nor to the technique or
mode of their administration
The mechanisms underlying tachyphylaxis are
open to debate and include changes in
pharmacokinetics or pharmacodynamics
Kottenberg-Assenmacher & Peters, 1999
Take home message!

44. Why do we get anesthetic failures?
3. Effect of Inflammation on local tissues (pH)
4. Effect of Inflammation on blood flow – vasodilation
5. Effect of Inflammation on nociceptors – allodynia
6. Effect of Inflammation on central sensitization
7. Psychological factors
Hargreaves 2002
7. Genetic factors - variations in drug metabolic genes

45. WHO Analgesic Ladder
Analgesic Ladder. World Health Organization; 1986

46. Typical situation
Patient comes back within 24 hours after a treatment
and complains of severe pain. You prescribe Tylenol 3.
Next morning the patient is back in your office with
acute pain and asks for stronger pain killer
• Is this real or he/she is a drug seeker?
• What should I prescribe to alleviate the pain ?

47. Q : Patient on Tylenol 3 reports only minor pain
relief
Next best treatment options:
A. Tylenol 4
B. Percocet
C. Oxycontin or Tramadol
D. Celecoxib

48. Tylenol 3 = acetaminophen (500mg) +codeine (30mg)
Non-responders
are poor CYP2D6
metabolizers
http://pharmgkb.blogspot.ca/2013/02/fda-to-post-black-box-warning-on-codeine.html

49. Tylenol 3 non-responders
• Poor CYP2D6 metabolizers CANNOT convert codeine to
morphine, thus do not experience pain relief.
• Oxycodone and Tramadol are metabolized by CYP2D6
• Percocet (acetaminophen and oxycodone) – the same!
• These patients do not benefit from Oxycodone,
Tramadol, Tramacet and Percocet
• Respond well to morphine and fentanyl, and COX-2
inhibitors
Take home message!

50. Q: Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is:
A. Tylenol 4
B. Oxycontin or Tramadol
C. Morphine
D. Celecoxib

51. Q: Patient on Tylenol 3 reports short-term pain
relief
Next best treatment option is:
A. Tylenol 4
B. Oxycontin or Tramadol
C. Morphine
D. Celecoxib
R

52. Patient on Tylenol 3 reports only short term
pain relief
Most likely the patient is ultrafast CYP2D6 metabolizer
Stamer & Stüber Expert Opin. Pharmacother. (2007)

53. Ethnic variability of CYP2D6 alleles
Stamer & Stüber Expert Opin. Pharmacother. (2007)

54. Acute Post-Endodontic Pain
Reported incidence – 1.6%
to 6.6% within one week
Typically treated with shortterm analgesics
Analgesics ineffective in 3% of affected patients
Al-Negrish et al. 2006, Imura et al. 1995, Morse et al. 1987, Trope 1991,
Walton & Fouad 1992

55. Persistent Post-Endodontic Pain
Reported incidence – 5.5 %
(range of 3-12%) beyond six
months
Estimated 3.4% is of nonodontogenic origin
In the US – 870,000, in Canada –96,000 -new cases/year;
In the US – 550,000, in Canada –61,000 non-odontogenic pain
Campbell et al. 1990, Marbach et al. 1982, Polycarpou et al. 2005, Keenan 2010,
Nixdorf et al. 2010, Cherkas &Sessle 2012

56. Analgesia
Postoperative analgesia is no different from
other areas of medicine, in that we all have
strong opinions, and often the stronger the
opinion the weaker is the underlying evidence.
HJ McQuay, DM, University of Oxford

57. Adverse side effects are rare and underreported
• Collecting evidence about harm in
postoperative pain receives much less
attention than evidence about efficacy….
• Rare (serious) adverse effects are not likely to
be detected in small randomised trials
• Adverse side effects create liability risk for
your practice!

58. Levels of evidence
Systematic
Reviews
Evidence
Synthesis &
Guidelines
Critically Apprised
Individual Articles
Filtered
information
Randomized Controlled Trials
Case-control Studies & Case Series
and reports
Background information / Expert Opinion
Unfiltered
information

59. The 2007 Oxford league
table of analgesic efficacy
Numbers needed to treat - the
proportion of patients with at
least 50% pain relief over 4-6
hours compared with placebo in
randomised, double-blind, singledose studies in patients with
moderate to severe pain.
http://www.medicine.ox.ac.uk/bandolier/boot
h/painpag/Acutrev/Analgesics/lftab.html
Analgesic
Number Percent
of
with at
patients
least
in
50%
comparis pain
on
relief
NNT
Dipyrone 1000
Ibuprofen 600/800
Ketorolac 20
Ketorolac 60 IM
Diclofenac 100
Piroxicam 40
Celecoxib 400
113
165
69
116
545
30
298
79
86
57
56
69
80
52
1.6
1.7
1.8
1.8
1.8
1.9
2.1
Paracetamol 1000
+ Codeine 60
197
57
2.2
Oxycodone IR 5 +
Paracetamol 500
150
60
2.2
370
675
60
279
247
288
5456
51
54
73
61
53
73
55
2.2
2.3
2.3
2.4
2.4
2.4
2.5
Bromfenac 25
Rofecoxib 50
Oxycodone IR 15
Aspirin 1200
Bromfenac 50
Dipyrone 500
Ibuprofen 400

60. What may work for Tylenol 3 non-responders?
1. COX2 inhibitors (valdecoxib, celecoxib)
2. Higher doses of ibuprofen
3. Anti-epileptic (carbamazepine or pregabalin)
4. Morphine
R

61. Effect of Acetaminophen on
Head Withdrawal Response (Animal Model)
Cherkas et al., 2013

62. Effect of Pregabalin on Head Withdrawal
Response (Animal Model)
0.18
0.14
0.12
0.1
Naïve
0.08
*
0.06
*
0.04
0.02
Time
Cherkas et al., 2013
Day 56
180m
120m
60m
Day 49 Pre
Day 42
Day 35
Day 28
Day 22
180m
120m
60m
Day21 Pre
Day 21
Day 14
Day 10
180m
120m
60m
Day7 Pre
Day 5
Day3
Day 1
0
Pre
Head withdrawal threshold
0.16
Aceta 100mg/Kg
PG 75mg/kg
IONX

63. Break - 10 min

64. Post-Endodontic Pain Terminology
Phantom tooth pain
Idiopathic periodontalgia
Idiopathic odontalgia
Atypical odontalgia
Pain in a tooth or tooth-bearing area
Not related to any dental cause
Often mistaken for toothache and treated as such
Marbach 1978, Harris 1978, Graff-Radford et al. 1986, Rees & Harris 1978, BaadHansen 2008, Zakrzewska 2010, 2011

65. Atypical Odontalgia
Specific mechanisms not yet established
Sub-set of trigeminal neuropathic pain: ”pain
arising as a direct consequence of any lesion or disease
affecting the somatosensory system”
Incidence can be as high as 3% to 6%
International Association for the Study of Pain 2011
Take home message!

66. What do we do for better anesthesia?
Alternate injection locations
• Gow-Gates and Vazirani-Akinosi
• Incisive nerve block at the mental foramen
• Mandibular infiltration following IANB
Supplemental LA
• Intraligamental
• Intrapulpal
• Intraosseus

67. Anesthetic efficacy of X-tip intraosseous injection using
2% lidocaine with epinephrine in patients with
irreversible pulpitis after inferior alveolar nerve block
• 93% of X-tip injections were successful
Verma et al., 2013
Take home message!

68. Al Reader et al; 2011

69. Al Reader et al; 2011

70. Q: In which of the following teeth it is highly unlikely to
have profound anesthesia after the IANB and
intraosseous injection?
1.
2.
3.
4.
5.
Tooth with symptomatic irreversible pulpitis
Tooth with asymptomatic irreversible pulpitis
Tooth with reversible pulpitis
Asymptomatic tooth with necrotic pulp
Symptomatic tooth with necrotic pulp and PA
radiolucency

71. Painful teeth with necrotic pulp and PA
radiolucencies
courtesy of Kamil Kolosowski

72. Painful teeth with necrotic pulp and PA
radiolucencies
• In this condition, intraosseous and intrapulpal
injections are painful and may not be effective
• Intraosseous and intrapulpal injections should
not be used in painful teeth with necrotic
pulps and radiolucent areas
Al Reader et al; 2011

73. Flare-up
 As specifically defined by Walton (2002),
interappointment flare-up has the following 4
criteria:
 1. Within a few hours to a few days after an
endodontic procedure, a patient has significant
increase in pain or swelling or a combination of
the two.
 2. The problem is of such severity that the
patient initiates contact with the dentist.

74. Flare-up
• 3. The dentist determines that the problem is
of such significance that the patient must
come for an unscheduled visit.
• 4. Active treatment is rendered. That may
include incision for drainage, canal
debridement, opening the tooth, prescribing
appropriate medications, or doing whatever is
necessary to resolve the problem.

75. Flare-up - Frequency
• Overall incidence low
• Best evidence suggest true frequency ranges
from 1.5% to 5.5%
• Some studies showing frequency high as 16%
• Variation due at least in part to study design
(prospective, retrospective), how cases
defined, sample size, etc.
Walton 2002, Siqueira and Barnett 2004

76. Causes of Post-op Pain
• Central sensitization
• Microbial
• Non-microbial
(mechanical or ‘physical’, chemical)
Seltzer and Naidorf 1985, Siqueira and Barnett 2004

77. Causes of Post-op Pain
• Microbial causes are the most common and
most important cause of post-operative pain
in endodontics
• Non-microbial causes (mechanical, chemical,
even thermal in rare instances) are typically
iatrogenic
Seltzer and Naidorf 1985, Siqueira and Barnett 2004

78. Clinical/Risk Factors for Post-op Pain or
Flare-Up
Related to Presenting Signs/Symptoms
– With pre-op pain  increased risk
– With pre-op swelling  increased risk
• With pre-op pain, increased stress levels may lead to
impaired immune capabilities
Logan et al 2001, Walton 2002

79. Clinical/Risk Factors for Post-op Pain or
Flare-Up
• Related to Treatment Procedures
– Single visit versus multi-visit – no difference in risk
(Sathorn 2008, Figini 2008)
– Incomplete debridement or overinstrumentation?
increased risk
– Obturation – decreases the risk?
May be due to fact that operators won’t obturate cases
with extreme presenting signs/symptoms
Walton 2002

80. Post-Operative Pain Control – Operative
Treatment
Choices:
– Re-instrumentation
– Cortical trephination
– Incision and drainage
– Intracanal medicaments
– Occlusal reduction
Siqueira and Barnett 2004

82. I think, the adequate working length is shown in ___?
A
B
1. A
2. B
3. C
4. B+C
5. None
C

83. I think, the adequate working length is shown in ___?
A
B
C

86. What is the best cell phone for my family?

87. EndoVac

88. Negative pressure
irrigation
Plazas-Garzon and Cherkas,
2013

89. Postoperative pain after the application of two different
irrigation devices in a prospective randomized clinical trial
Use of a negative apical pressure irrigation device can
result in a significant reduction of postoperative pain
levels in comparison to conventional needle irrigation.
Gondim E Jr et al., 2010

90. Post-Operative Pain Control –
Pharmacological Treatment
• Antibiotics
• Local Anesthetics
• Analgesics
– Acetaminophen
– NSAIDs
– Opioid analgesics

91. Q: Post-Operative Pain Control Antibiotics
• Are systemtic antibiotics effective in relieving
‘untreated’ pulpal pain?
• Answer: NO
• Nagle et al 2000 (penicillin had no analgesic
effect in cases of irrversible pulpitis)
Fouad 2002

92. Q: Post-Operative Pain Control Antibiotics
• Question: Are systemtic antibiotics effective in
relieving localized post-op periapical
symptoms?
• Answer: NO
– In patients with pulp necrosis and symptomatic
AP, addition of systemic penicillin provided no
added benefit to the painful condition beyond
that of chemomechanical canal instrumentation
alone
Fouad 2002, Henry et al 2001

93. What DOESN’T Work for Post-Op Pain?
1. Antibiotics
Walton and Chiappinelli (JOE ’97), Fouad,
Rivera and Walton (OOOO, 96), Henry, Reader
and Beck (JOE, 2001)
Effect on incidence of flare ups, Pickenpaugh,
Reader et al (JOE, 2001)
2. Narcotics as a first choice medication
Systematic reviews (Moore et al, 2005-13)

94. Indications for Antibiotics Use in
Endodontics
• AHA Prophylaxis
• Diffuse swelling (cellulitis)
• Localized swelling without drainage
• Rapidly increasing swelling
• Systemic signs (fever, lymphadenopathy,
unexplained trismus)
• Trauma
• Regeneration
Take home message!

95. Q: You are considering to prescribe a
macrolide antibiotic
Your major concerns are:
a) Patient's prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c

96. Q: You are considering to prescribe a
macrolide antibiotic
Your major concerns are:
a) Patient's prior sensitivity to clarithromycin or
azithromycin
b) Kidney and liver function
c) Use of statins
d) a+b
e) a+b+c

97. Antibiotics : Be aware of statins
rs4149056 p.Val174Ala
SLCO1B1
18% of statin users
experience muscle pain as a
result of rhabdomyolysis that
may lead to kidney failure
Macrolides can exacerbate
the risk of kidney failure
especially in elderly, and
patients with reduced kidney
function
Link E, Parish S, Armitage J, Bowman L, Heath S, Matsuda F, Gut I,
Lathrop M, and Collins R. (2008) The SEARCH Collaborative Group. "
N. Engl. J. Med. 359:789-799.

98. Azythromycin has a lower risk of statin
interaction
Azithromycin
Clarithromycin
Erythromycin
http://www.pharmgkb.org/pathway/PA145011109

99. Statins and microlides can lead to kidney
failure
Statin toxicity from macrolide antibiotic coprescription: a populationbased cohort study.
Patel AM, Shariff S, Bailey DG, Juurlink DN, Gandhi S, Mamdani M, Gomes T, Fleet J, Hwang YJ, Garg AX
Ann Intern Med. 2013 Jun 18;158(12):869-76
“Compared with azithromycin, coprescription of a
statin with clarithromycin or erythromycin was
associated with a higher risk for hospitalization with
rhabdomyolysis or with acute kidney injury”
• Patients reporting muscle pain while taking
statins are at increased risk of kidney damage
while on macrolides
• thus should temporarily discontinue statins

100. Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy?
1.
2.
3.
4.
Preoperative hyperalgesia
Females
Apical Periodontitis
Necrotic Pulp
Hutter and Hargreaves, (2011)

101. Can We Predict Patients More Likely to
Experience Pain After an Endodontic Therapy?
1. Pre-op pain is a good predictor or post-op pain
2. On average pain is maximal in first 24-48 hrs –
no need to give pain meds for more than a few
days with proper clean and shape of the canal
Torabinejad et al., (JOE, 2002)

102. Post-Operative Pain Control – Local
Anesthetics
• LA can be used for sole purpose of pain relief
or in conjunction with operative/surgical
procedures to reduce post-op pain
• Most useful in cases involving mandibular
teeth where bupivacaine (long-acting LA) is
administered by mandibular block injection

103. Post-Operative Pain Control – Local
Anesthetics
• bupivacaine 0.5%
– available with 1:200,000 epinephrine
– trade name Marcaine (Vivacaine – new, U.S. only)
www.kodakdental.com

104. Post-Operative Pain Control – Local
Anesthetics
Haas 2002

105. Bupivacaine-induced cardio toxicity
Minimum Intravenous Toxic
Dose of Local Anesthetic
Agent
Minimum
Toxic Dose
(mg/kg)
Procaine
19.2
Tetracaine
2.5
Chloroprocain
e
22.8
Lidocaine
6.4
Mepivacaine
9.8
Bupivacaine
1.6
Etidocaine
3.4
Excessive plasma concentrations due to:
– inadvertent intravascular injection,
– excessive dose or rate of injection,
– administration into vascular tissue,
– delayed drug clearance (CYP3A4).
Myocardial depression and bradycardia,
and cardiovascular collapse
Goldfrank LR, et al. 1507-17. In: Goldfrank's
Toxicologic Emergencies. 6th ed. New York:
McGraw-Hill; 1998:897-903.

106. The 3D Strategy for Treating Endodontic Pain
1. Differential Diagnosis of non odontogenic pain:
P – Psychogenic – Munchausen's
I – Inflammatory – Sinusitis
N – Neurovascular – Cluster headaches
S – Systemic – Myocardial Infarct
M – Musculoskeletal – Myofacial pain (TMD)
Hargreaves 2011

107. The 3D Strategy for Treating Endodontic Pain
2. Definitive Dental Treatment
• anesthesia (anatomy, all current evidence based
techniques)
• EndoVac (negative pressure), Bupivacaine, etc.
3. Drugs
• NSAIDs
• Opioids
Hargreaves, 2011

108. Post-Operative Pain Control: Analgesics –
Algorithm
Hargreaves and Seltzer 2002

109. Preferred for patients on
warfarin or other blood
thinners
Poor CYP2C9 metabolizers
experience better pain relief
vs
CYP2E1 converts acetaminophen into
N-acetyl-p-benzoquinoneimine
(NAPQI)
• NAPQI is the active metabolite
• increases risk of liver toxicity
Inactivated by
CYP2C9
•
•
•
•
Celecoxib
Lornoxicam
Diclofenac
Naproxen
•
•
•
•
Ketoprofen
Piroxicam
Meloxicam
Suprofen

110. Acetominophen and Ibuprofen
Substantially greater analgesia than either drug
alone AND avoids the side effects of opiates
Cooper et al: combined Ibuprofen 200 mg + APAP
650 (Compendium) was better than either alone
Derry et al., 2011(Br Dent j, 2011)
Mehninick (IEJ, 2004)

111. Cox-2 specific inhibitors
• Very effective in controlling inflammatory pain
• Long term exposure leads to increased risk of
heart failure
• Most effective Cox-2 blockers were pulled off the
market
• How to balance benefits and risks?

112. Coxibs: pain relief and risk of CVD and GI bleed
• Coxibs metabolized by CYP2C9
• Poor metabolizers have increased
exposure to celecoxib
• better pain control
• increased risk of heart attack
and GI bleeding
• Warfarin is metabolized by CYP2C9
• Co-administration can increase risk
of intracranial bleeding
• Need to check the INR
http://www.pharmgkb.org/pathway/PA165816736
Gong Li, et al. 2012

113. Post-Operative Pain Control –
ASA (low dose) and ibuprofen
Because of an interaction between ibuprofen
and ASA, an alternative NSAID should be used,
or ibuprofen should be taken at least 30 min
after or at least 8 h before ASA
AHA, 2007

114. Before recommending NSAIDs for pain control
Ask the patient whether:
a. Suffering from ulcers or GI bleeding
b. Abusing alcohol or has reduced liver function
c. Taking aspirin or antiplatelet medication (Plavix,
Effient)
d. Warfarin or another anticoagulant (Xarelto)
• Advise to check INR with family physician to adjust
warfarin dose to reduce the risk on intracranial bleed
• Seek advise if pain persists over 3 days
Take home message!

115. Post-Operative Pain Control – Steroids
• Glucocorticoids inhibit many cells and factors
present in inflammatory response
• Inhibition of gene transcription for
inflammatory factors
• Inhibition of pro-inflammatory cytokine
production
Marshall 2002

116. Post-Operative Pain Control – Steroids
“The administration of systemic steroids is efficacious as an
adjunct to but not replacement for appropriate endodontic
treatment in the attenuation of endodontic post treatment pain”
“Systemic steroids are also highly effective in those patients who
present for treatment with moderate/ severe pain and a clinical
diagnosis of pulpal necrosis with associated periapical
radiolucency.”
Marshall 2002

117. Post-Operative Pain Control – Steroids
Is the benefit worth the risk, given the side
effect profile (ex. avascular necrosis of the hip
from a single oral steroid dose) and given the
efficacy of available analgesics?

118. Atypical odontalgia
Cherkas and Sessle, 2012

119. Pain Associated with Irreversible Pulpitis
What is the best time for treatment?
Acute inflammation
Acute inflammation

120. Today (2013-14)
Today’s patients are under the impression
that only classic methods of pain control
apply to endodontics
We now have “molecular approaches” that
offer us different methods of pain control

121. Today (2013-14)
http://www.personalizedmedicinecoalition.org/

122. DNA tests – can predict drug response
and the risk of side effects

123. Conclusion
 Post-operative pain and flare-up





Definitions/Frequency (25-40% vs 2-6%)
Causes – bacterial, chemical, physical
Clinical / Risk Factors
Prevention – may not be entirely possible
Temporal summation (central sensitization)
 Post-Operative Pain Control (Management)




Operative/surgical – reinstrumentation, I&D, etc.
Pharmacological – analgesics, LA (steroids, Ab)
Patients respond differently to treatments
Adverse side effects are preventable

124. Future directions
• More targeted pain treatments (minocycline?)
• Proactive interventions to reduce the risk of
chronic pain
• Implementation of new endodontic techniques
• Personalized approach to pain management
• Reduced incidence of adverse side effects
• Happier and healthier patients!

125. Thank you
Pavel Cherkas
pavel@endoart.ca
EndoArt.ca
Ruslan Dorfman
ruslan@geneyouin.ca
www.geneyouin.ca
Phone: 647-868-1812
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