archives of oral biology 60 (2015) 973–981
Available online at www.sciencedirect.com
ScienceDirect journal homepage: http://www.elsevier.com/locate/aob
Effect of topical anaesthesia in patients with persistent dentoalveolar pain disorders: A quantitative sensory testing evaluation Andre´ Luı´s Porporatti a,*, Yuri Martins Costa a, Juliana Stuginski-Barbosa a, Leonardo Rigoldi Bonjardim b, Paulo Ce´sar Rodrigues Conti a a b
Department of Prosthodontics, Bauru School of Dentistry, University of Sa˜o Paulo, Bauru, Brazil Department of Biological Sciences, Bauru School of Dentistry, University of Sa˜o Paulo, Bauru, Brazil
article info
abstract
Article history:
Objective: The aim of this study was to test the hypothesis that patients with persistent
Accepted 28 February 2015
dentoalveolar pain disorder (PDAP) expresses somatosensory abnormalities through quan-
Keywords:
PDAP do not have somatosensory alterations after application of a topical anaesthetic gel.
titative sensory testing (QST), when compared to healthy controls; and that individuals with Persistent dentoalveolar pain
Design: QST was performed in 25 subjects with PDAP (19 women and 6 men), at baseline and
disorder
after topical application of benzocaine 2% (Benzotop 200 mg/g, DFL) and compared to 25
Atypical odontalgia
matched healthy controls. After ‘‘Z’’ score transformation, results were analyzed using the
Persistent pain
paired ‘‘t’’ test and ‘‘t’’ test with significance level of 5%.
Neurosensory test
Results: PDAP subjects have lower pain detection thresholds confirmed through mechanical
Quantitative sensory testing
tests; and higher pain intensity report through thermal stimuli tests (heat and cold) when compared to healthy subjects. Topical anaesthesia partially reduces in 60% pain intensity of PDAP patients; and anaesthetic gel increases mechanical detection thresholds and reduces pain intensity report in dynamical mechanical allodynia tests. Conclusions: PDAP patients had abnormal thermal sensory and mechanical allodynia, which is indicative of central sensitization. Moreover, topical anaesthetic incited a significant reduction in pain intensity, and an increase in mechanical and pain detection thresholds, which could be also suggestive of a peripheral disorder. # 2015 Elsevier Ltd. All rights reserved.
1.
Introduction
PDAP (persistent dentoalveolar pain disorder) is a chronic neuropathic condition that is characterized by a continuous and severe pain located in the dentoalveolar region innervated
by the trigeminal nerve that is not caused by any other disease and is identified through clinical and image examination.1–4 PDAP occurs in 3–6% of patients who receive dentistry management. Traumatic injury, periodontal surgery, endodontic therapy, apicectomy, tooth extraction or the slightest trauma during tooth preparation or inferior alveolar nerve
* Corresponding author at: Department of Prosthodontics, Bauru School of Dentistry, University of Sa˜o Paulo, Al. Octa´vio Pinheiro Brizolla 9-75, CEP 17012-901, Vila Universita´ria, Bauru, SP, Brazil. Tel.: +55 14 981152914. E-mail addresses: [email protected], [email protected] (A.L. Porporatti). http://dx.doi.org/10.1016/j.archoralbio.2015.02.027 0003–9969/# 2015 Elsevier Ltd. All rights reserved.
974
archives of oral biology 60 (2015) 973–981
block that damage nerve fibres may disrupt peripheral afferent nerve impulses.5–11 Sensory deficits due to a deprivation of afferent impulses is known as deafferentation,12 and it is expressed clinically by somatosensory abnormalities, such as allodynia, hyperalgesia and pain exacerbation by thermal, mechanical and/or chemical stimuli.13,14 The role of peripheral or central sensitization mechanisms in neuropathic disorders is complex and not fully understood. Diagnostic local anaesthesia is recommended to elucidate the source of pain and its mechanisms.13,15 One previous study demonstrated neuropathic pain relief after a peripheral anaesthesia block with lidocaine,16 but the effect of a topical anaesthetic gel in patients with PDAP has not been investigated. Evidence indicates that a peripheral lidocaine injection may block sodium channels because of its deep penetration.17,18 However, whether the same effect occurs after an anaesthetic gel application, which likely has a more superficial action, is not known. Somatosensory abnormalities may be assessed using QST (quantitative sensory testing), which comprehensively evaluates the nervous system.12,19 QST uses mechanical (static or dynamic), thermal, electrical and chemical tests. The static mechanical test detects thresholds to innocuous and/or harmful stimuli, and the dynamic mechanical test explores allodynia and temporal summation. Thermal detection thresholds evaluate innocuous and/or harmful thermal stimuli (cold, warm or hot).20–22 This study tested the hypotheses that patients with PDAP express somatosensory abnormalities compared to healthy subjects (controls) that are detectable using QST and that patients with PDAP do not have somatosensory alterations after the application of a topical anaesthetic gel.
2.
Materials and methods
This controlled clinical trial was conducted from September 2011 to December 2012. Somatosensory abnormalities were investigated in a sample of clinical patients with PDAP before (baseline) and after topical anaesthesia and compared to healthy controls.
2.1.
Persistent pain that is present at least 8 h per day for 15 days or more per month for 3 months duration. Localized in dentoalveolar area in which the maximum pain is defined within an anatomical area. Not caused by another disease or disorder after dental, neurological examination and imaging. A CBCT (cone beam computed tomography) was requested in patients when some diagnostic doubt remained after the complementary exams and radiographs.23 Patients taking pain medications were also included in the study. Exclusion criteria included the presence of previously diagnosed systemic conditions, such as diabetes, uncontrolled hypertension, leprosy and/or disabling neurological and psychological disorders.13,24,25 For a more accurate trial, psychosocial features were evaluated thought specific questionnaires. Depression and anxiety symptoms were assessed using the Beck Depression Inventory (BDI)26–29 and Beck Anxiety Inventory (BAI),26,27,30 respectively. Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality.31–33 Controls were selected from volunteers who had undergone dental therapy in the Prosthodontics Section of Bauru School of Dentistry, University of Sa˜o Paulo. Controls could not have previously received a PDAP diagnosis and needed to be free from any type of pain, dental pathology or therapy for at least 6 months.34 All participants signed an informed consent form that was approved by the Academic Investigation Review Board (Protocol 081/2011). Initially, a total of 47 patients with a diagnostic hypothesis of PDAP were selected, but only 25 patients met the inclusion criteria. Nineteen patients were excluded because they did not meet the required diagnostic criteria for PDAP, 16 patients had a diagnosis of acute irreversible pulpitis, and three patients had tooth fractures. Three patients were excluded because they fulfilled one or more exclusion criteria (two patients had uncontrolled diabetes, and one patient had hypertension) (Fig. 1). An age- and gender-matched control group of 25 healthy subjects was formed after selection of the 25 consecutive eligible patients with PDAP.
Sample 2.2.
Patients with PDAP were selected at the Orofacial Pain Service of the Bauru School of Dentistry, University of Sa˜o Paulo, Brazil. All patients who were seeking treatment for dental pain and were aged 18–65 years were invited to participate. All patients with a suspected initial diagnosis of PDAP underwent an anamnesis, physical examination and panoramic and periapical radiographs. Anamnesis included personal data history, chief complaint, and medical and dental histories. Medical history included questions relating to the pain severity and quality of the main complaint, worsening and improvement factors, accompanying symptoms and previous treatments. Orofacial pain specialists (ALP, YMC, JSB) diagnosed PDAP during the first patient consultation, which was prior to enrollment in the study. PDAP was diagnosed according the following criteria1:
Methods
A sequence of seven QSTs was performed at baseline for both groups. QSTs were applied over the alveolar mucosa in the apical tooth area for the PDAP group. This dentoalveolar area was approximately 7 mm.2 Maxillar or mandibular regions were matched in the control group. The dentoalveolar mucosa used was the closest region to the tooth (attached gingiva).20,35 QST was also performed in the PDAP group 5 min after the topical application of an anaesthetic gel (benzocaine – Benzotop 200 mg/g – FL1). Approximately 5 mg of benzocaine was applied on the dentoalveolar mucosa and dried with compressed air. Benzocaine remained on the mucosa for 10–15 s, and it was removed. QSTs were performed again after 2 min. The temperature of the topical anaesthetic gel was 25 8C.
archives of oral biology 60 (2015) 973–981
975
Fig. 1 – Flowchart of exclusion criteria for the selected patients.
Pain intensity in the PDAP group was recorded at baseline and after anaesthetic gel application using a visual analogue scale (VAS).20 VAS consisted of a horizontal line, 100 mm long, anchored by word descriptors at each end; the far left read ‘‘no pain’’ and the right read ‘‘worst pain imaginable’’. Patients were requested to make a vertical mark on the VAS line at the point that they felt represented their perception of their current pain state.36
2.2.1.
QST (quantitative sensory testing)
The sequence explained below was the order of QST used in this study.
2.2.1.1. MDT (mechanical detection threshold). This test used von Frey monofilaments that were adapted to define tactile fibre thresholds.37 Twenty von Frey nylon monofilaments with different diameters were used and calibrated to exert specific forces when bending. Monofilament force varied from 0.008 g/mm2 to 300 g/mm2.37 Each monofilament was applied perpendicularly to the dentoalveolar region, and a slight pressure was made until the filament bent. The method of limits was used in which approximately 6–8 ascending/descending stimuli were applied, and the average force was calculated.38 MDT estimated the least von Frey nylon monofilament force that subjects were able to appropriately recognize.37 2.2.1.2. PDT (pain detection threshold). This test estimated the least von Frey filament force for which patients reported a painful sensation. The method of limits used in MDT was also applied for PDT. Patients identified the filament, and their pain intensity was recorded using VAS.20 2.2.1.3. DMA1 (dynamical mechanical allodynia with a cotton swab) and DMA2 (dynamical mechanical allodynia with a toothbrush). A slight vibration of a cotton swab (DMA1) and a soft toothbrush (DMA2) was applied to alveolar mucosa for 10 s for the study group only, and the pain intensity was recorded with VAS.20 The stimulus area was approximately 2 mm2 and 5 mm2 for the cotton swab and toothbrush, respectively. DMA is not detectable in healthy patients, so it was not tested on control group.
2.2.1.4. CPS (cold pain sensation) and HPS (heat pain sensation). A rod of aluminium (7-mm diameter) was placed in a container with ice at 0 8C (CPS) or hot water at 53 8C (HPS) for 1 min, and it was applied to the alveolar mucosa for approximately 4 s. Pain intensity was recorded using the VAS.39
2.2.1.5. WUR (wind-up ratio). This test was conducted using repeated application of the 5.46 g von Frey filament in a continuous 30-s sequence (force of 26 g/mm2, approximately one stimulus per second). Patients rated the pain intensity four times on an NRS (numeric rating scale) at the 1st second, 10th second, 20th second and 30th second. The NRS is a 0–10 point scale, and patients were asked to rate their pain from 0 to 10. A score of 0 indicates ‘‘no pain’’, and 10 is the ‘‘worst pain imaginable’’.40,41 WUR was determined using ratio calculations (painfulness of the first pinprick stimulation vs. painfulness of a train of 30th seconds of pinprick stimulations), and a single value was established. 2.2.2.
Data reduction and analysis
The ‘‘Z’’ score transformation was performed to standardize QST values and obtain a single value for each test for comparison with control subjects.22 (‘‘Z’’ score calculation = Xsingle patient Meancontrols/Standard Deviationcontrols). In the first analysis, the ‘‘X’’ value was used for the PDAP patient at baseline and the ‘‘controls’’ were healthy subjects. In the second analysis, the ‘‘X’’ value was used for the PDAP patients after anaesthesia and the ‘‘controls’’ were PDAP patients at baseline. QST values from each patient were transformed to ‘‘Z’’scores as described by Rolke et al.22 A score above 1.96 or below 1.96 fell outside the 95% confidence interval of the mean reference value, and these scores were considered sensory abnormalities. Abnormalities were subsequently categorized as a sensory gain or sensory loss. Statistical analysis was performed using the paired ‘‘t’’ test (after the Kolmogorov–Smirnov normality test) to verify significant differences between the PDAP site at baseline and after topical anaesthesia. The ‘‘t’’ test was used to identify differences between the PDAP and control groups. The results were considered significant at a level of 5%.
976
3.
archives of oral biology 60 (2015) 973–981
intensity increased after 30 s of repeated stimuli, and no differences were found in the ratios between 1st and 30th seconds for both groups (Table 2). Spontaneous pain at baseline dropped from 62.5 mm to 25.1 mm after topical anaesthetic gel application ( p < 0.001; CI = 2.671; 4.812). The topical anaesthesia showed approximately 60% reduction in pain intensity. Topical anaesthesia on QST increased the mechanical detection thresholds to tactile (MDT) and painful stimuli (PDT) and decreased the pain intensity reported for dynamic mechanical allodynia tests (DMA1 and DMA2) and the windup test (30 s of repeated stimuli) (Fig. 2). However, the pain intensity of hot and cold stimuli did not differ after topical anaesthesia (CPS and HPS) (Fig. 2). ‘‘Z’’ scores using ‘‘PDAP data at baseline’’ as case and ‘‘health subjects data’’ as control indicated a gain in function (positive ‘‘Z’’ score) in dynamic mechanical allodynia (DMA1 and DMA2) and heat and cold thermal tests (CPS and HPS) (Fig. 3). The other ‘‘Z’’ score comparison considered the ‘‘after anaesthesia data’’ as the case and ‘‘baseline data’’ as control in the PDAP group (Fig. 3). A gain in function after topical anaesthesia was observed for some patients in mechanical detection (MDT) and mechanical pain detection (PDT) threshold
Results
Patients with PDAP were mainly women (76%), with a mean age of 58.25 years (SD = 12.17) and mean pain duration of 42.33 months (range 09–120 months). The healthy controls were formed of 19 women and six men with a mean age of 58.92 (SD = 7.39). The most affected pain region was the mandibular region (64% of patients with PDAP, 16 mandible and nine maxilla). Eighty percent of the involved teeth were posterior and 60% were in the right side. This percentage was matched to the control group. In this study, 56% of PDAP patients had extracted teeth, and 44% had endodontic treatment (Table 1). Accordingly to Table 1, 80% of PDAP group presented psychosocial profiles consistent with depression features, 76% anxiety features and 80% with poor sleep quality, while 71.5% of healthy subjects had absent of depression features, 90.5% had no anxiety features and 58% had good sleep quality, evaluated through specific questionnaires. The mean results for QST are shown in Fig. 2 and Table 2. Patients with PDAP had lower pain detection thresholds (PDT) and higher pain intensity after heat and cold stimuli (HPS and CPS) than the controls. Wind-up data showed that pain
Table 1 – Sample characteristics of patients with PDAP. PDAP patient
Tooth
Pain intensity (on VAS)
Pain duration (on Months)
Depression features
Anxiety features
Poor sleep quality
Prior dentistry management
Drugs used per day
CBCT
1 2 3 4 5
34 45 16 38 11
23 48 24 36 57
24 24 120 36 12
Yes Yes Yes No Yes
No Yes Yes No Yes
Yes Yes Yes No Yes
Endodontics Endodontics Tooth extraction Tooth extraction Tooth extraction
No Yes Yes Yes Yes
6 7
21 38
94 100
7 18
Yes Yes
Yes No
Yes Yes
Tooth extraction Tooth extraction
8 9 10 11
45 36 32 24
71 96 54 72
18 36 6 72
Yes Yes Yes Yes
Yes Yes Yes Yes
No Yes Yes Yes
Tooth extraction Tooth extraction Tooth extraction Endodontics
12 13 14 15 16 17
34 46 44 46 15 36
83 83 100 49 51 90
48 36 60 90 72 36
No Yes Yes Yes No Yes
No Yes Yes Yes No Yes
No Yes Yes Yes No Yes
Endodontics Endodontics Endodontics Endodontics Endodontics Extraction
18 19 20 21 22 23 24 25
27 24 46 36 33 15 36 13
50 64 41 70 60 35 49 60
7 24 36 90 48 90 6 42
Yes Yes Yes No No Yes Yes Yes
Yes Yes Yes Yes No Yes Yes Yes
Yes Yes Yes No Yes Yes Yes Yes
Tooth extraction Tooth extraction Tooth extraction Tooth extraction Tooth extraction Endodontics Endodontics Endodontics
None None None None Amitriptyline 25 mg/Carbamazepin 50 mg/Gabapentin 300 mg) None Gabapentin 300 mg/Duloxetine 30 mg None Gabapentin 200 mg None Topiramate 25 mg/Alprazolam 1 mg None None None None Nimesulide 100 mg Gabapentin 200 mg/Carbamazepin 200 mg Carbamazepin 200 mg None Gabapentin 150 mg None None Sertraline 50 mg Gabapentin 600 mg Carbamazepin 400 mg
No Yes
Yes No No Yes
No No No Yes Yes No
Yes Yes No No No Yes No Yes
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archives of oral biology 60 (2015) 973–981
Fig. 2 – Mean values of QST in the PDAP group (at baseline and after topical anaesthesia) and the control group (at baseline). QST: quantitative sensory testing; MDT: mechanical detection threshold; PDT: pain detection threshold; DMA1: dynamic mechanical allodynia with a cotton swab and DMA2: with toothbrush; CPS: cold pain sensation; HPS: heat pain sensation; WUR: wind-up ratio; VAS: visual analogue scale; s: seconds; mm: millimetre; *p < 0.05.
Table 2 – Mean pain intensity (VAS) recorded in the first, 10th, 20th and 30th second and variation between the first second and 30th second for wind-up ratio (WUR). Group/time
PDAP at baseline PDAP after anaesthesia Control
1st(SD)
10th(SD)
20th(SD)
30th(SD)
Variation between 1st and 30th second
p (CI) between 1st and 30th
2.54 (1.99) 1.88 (2.34) 2.16 (1.97)
4.75 (2.64) 3.13 (2.93) 3.86 (2.29)
5.75 (2.62) 4.38 (3.28) 5.02 (2.4)
6.50 (2.96) 5.39 (3.45) 5.82 (2.70)
3.96 3.51 3.66
Available online at www.sciencedirect.com
ScienceDirect journal homepage: http://www.elsevier.com/locate/aob
Effect of topical anaesthesia in patients with persistent dentoalveolar pain disorders: A quantitative sensory testing evaluation Andre´ Luı´s Porporatti a,*, Yuri Martins Costa a, Juliana Stuginski-Barbosa a, Leonardo Rigoldi Bonjardim b, Paulo Ce´sar Rodrigues Conti a a b
Department of Prosthodontics, Bauru School of Dentistry, University of Sa˜o Paulo, Bauru, Brazil Department of Biological Sciences, Bauru School of Dentistry, University of Sa˜o Paulo, Bauru, Brazil
article info
abstract
Article history:
Objective: The aim of this study was to test the hypothesis that patients with persistent
Accepted 28 February 2015
dentoalveolar pain disorder (PDAP) expresses somatosensory abnormalities through quan-
Keywords:
PDAP do not have somatosensory alterations after application of a topical anaesthetic gel.
titative sensory testing (QST), when compared to healthy controls; and that individuals with Persistent dentoalveolar pain
Design: QST was performed in 25 subjects with PDAP (19 women and 6 men), at baseline and
disorder
after topical application of benzocaine 2% (Benzotop 200 mg/g, DFL) and compared to 25
Atypical odontalgia
matched healthy controls. After ‘‘Z’’ score transformation, results were analyzed using the
Persistent pain
paired ‘‘t’’ test and ‘‘t’’ test with significance level of 5%.
Neurosensory test
Results: PDAP subjects have lower pain detection thresholds confirmed through mechanical
Quantitative sensory testing
tests; and higher pain intensity report through thermal stimuli tests (heat and cold) when compared to healthy subjects. Topical anaesthesia partially reduces in 60% pain intensity of PDAP patients; and anaesthetic gel increases mechanical detection thresholds and reduces pain intensity report in dynamical mechanical allodynia tests. Conclusions: PDAP patients had abnormal thermal sensory and mechanical allodynia, which is indicative of central sensitization. Moreover, topical anaesthetic incited a significant reduction in pain intensity, and an increase in mechanical and pain detection thresholds, which could be also suggestive of a peripheral disorder. # 2015 Elsevier Ltd. All rights reserved.
1.
Introduction
PDAP (persistent dentoalveolar pain disorder) is a chronic neuropathic condition that is characterized by a continuous and severe pain located in the dentoalveolar region innervated
by the trigeminal nerve that is not caused by any other disease and is identified through clinical and image examination.1–4 PDAP occurs in 3–6% of patients who receive dentistry management. Traumatic injury, periodontal surgery, endodontic therapy, apicectomy, tooth extraction or the slightest trauma during tooth preparation or inferior alveolar nerve
* Corresponding author at: Department of Prosthodontics, Bauru School of Dentistry, University of Sa˜o Paulo, Al. Octa´vio Pinheiro Brizolla 9-75, CEP 17012-901, Vila Universita´ria, Bauru, SP, Brazil. Tel.: +55 14 981152914. E-mail addresses: [email protected], [email protected] (A.L. Porporatti). http://dx.doi.org/10.1016/j.archoralbio.2015.02.027 0003–9969/# 2015 Elsevier Ltd. All rights reserved.
974
archives of oral biology 60 (2015) 973–981
block that damage nerve fibres may disrupt peripheral afferent nerve impulses.5–11 Sensory deficits due to a deprivation of afferent impulses is known as deafferentation,12 and it is expressed clinically by somatosensory abnormalities, such as allodynia, hyperalgesia and pain exacerbation by thermal, mechanical and/or chemical stimuli.13,14 The role of peripheral or central sensitization mechanisms in neuropathic disorders is complex and not fully understood. Diagnostic local anaesthesia is recommended to elucidate the source of pain and its mechanisms.13,15 One previous study demonstrated neuropathic pain relief after a peripheral anaesthesia block with lidocaine,16 but the effect of a topical anaesthetic gel in patients with PDAP has not been investigated. Evidence indicates that a peripheral lidocaine injection may block sodium channels because of its deep penetration.17,18 However, whether the same effect occurs after an anaesthetic gel application, which likely has a more superficial action, is not known. Somatosensory abnormalities may be assessed using QST (quantitative sensory testing), which comprehensively evaluates the nervous system.12,19 QST uses mechanical (static or dynamic), thermal, electrical and chemical tests. The static mechanical test detects thresholds to innocuous and/or harmful stimuli, and the dynamic mechanical test explores allodynia and temporal summation. Thermal detection thresholds evaluate innocuous and/or harmful thermal stimuli (cold, warm or hot).20–22 This study tested the hypotheses that patients with PDAP express somatosensory abnormalities compared to healthy subjects (controls) that are detectable using QST and that patients with PDAP do not have somatosensory alterations after the application of a topical anaesthetic gel.
2.
Materials and methods
This controlled clinical trial was conducted from September 2011 to December 2012. Somatosensory abnormalities were investigated in a sample of clinical patients with PDAP before (baseline) and after topical anaesthesia and compared to healthy controls.
2.1.
Persistent pain that is present at least 8 h per day for 15 days or more per month for 3 months duration. Localized in dentoalveolar area in which the maximum pain is defined within an anatomical area. Not caused by another disease or disorder after dental, neurological examination and imaging. A CBCT (cone beam computed tomography) was requested in patients when some diagnostic doubt remained after the complementary exams and radiographs.23 Patients taking pain medications were also included in the study. Exclusion criteria included the presence of previously diagnosed systemic conditions, such as diabetes, uncontrolled hypertension, leprosy and/or disabling neurological and psychological disorders.13,24,25 For a more accurate trial, psychosocial features were evaluated thought specific questionnaires. Depression and anxiety symptoms were assessed using the Beck Depression Inventory (BDI)26–29 and Beck Anxiety Inventory (BAI),26,27,30 respectively. Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality.31–33 Controls were selected from volunteers who had undergone dental therapy in the Prosthodontics Section of Bauru School of Dentistry, University of Sa˜o Paulo. Controls could not have previously received a PDAP diagnosis and needed to be free from any type of pain, dental pathology or therapy for at least 6 months.34 All participants signed an informed consent form that was approved by the Academic Investigation Review Board (Protocol 081/2011). Initially, a total of 47 patients with a diagnostic hypothesis of PDAP were selected, but only 25 patients met the inclusion criteria. Nineteen patients were excluded because they did not meet the required diagnostic criteria for PDAP, 16 patients had a diagnosis of acute irreversible pulpitis, and three patients had tooth fractures. Three patients were excluded because they fulfilled one or more exclusion criteria (two patients had uncontrolled diabetes, and one patient had hypertension) (Fig. 1). An age- and gender-matched control group of 25 healthy subjects was formed after selection of the 25 consecutive eligible patients with PDAP.
Sample 2.2.
Patients with PDAP were selected at the Orofacial Pain Service of the Bauru School of Dentistry, University of Sa˜o Paulo, Brazil. All patients who were seeking treatment for dental pain and were aged 18–65 years were invited to participate. All patients with a suspected initial diagnosis of PDAP underwent an anamnesis, physical examination and panoramic and periapical radiographs. Anamnesis included personal data history, chief complaint, and medical and dental histories. Medical history included questions relating to the pain severity and quality of the main complaint, worsening and improvement factors, accompanying symptoms and previous treatments. Orofacial pain specialists (ALP, YMC, JSB) diagnosed PDAP during the first patient consultation, which was prior to enrollment in the study. PDAP was diagnosed according the following criteria1:
Methods
A sequence of seven QSTs was performed at baseline for both groups. QSTs were applied over the alveolar mucosa in the apical tooth area for the PDAP group. This dentoalveolar area was approximately 7 mm.2 Maxillar or mandibular regions were matched in the control group. The dentoalveolar mucosa used was the closest region to the tooth (attached gingiva).20,35 QST was also performed in the PDAP group 5 min after the topical application of an anaesthetic gel (benzocaine – Benzotop 200 mg/g – FL1). Approximately 5 mg of benzocaine was applied on the dentoalveolar mucosa and dried with compressed air. Benzocaine remained on the mucosa for 10–15 s, and it was removed. QSTs were performed again after 2 min. The temperature of the topical anaesthetic gel was 25 8C.
archives of oral biology 60 (2015) 973–981
975
Fig. 1 – Flowchart of exclusion criteria for the selected patients.
Pain intensity in the PDAP group was recorded at baseline and after anaesthetic gel application using a visual analogue scale (VAS).20 VAS consisted of a horizontal line, 100 mm long, anchored by word descriptors at each end; the far left read ‘‘no pain’’ and the right read ‘‘worst pain imaginable’’. Patients were requested to make a vertical mark on the VAS line at the point that they felt represented their perception of their current pain state.36
2.2.1.
QST (quantitative sensory testing)
The sequence explained below was the order of QST used in this study.
2.2.1.1. MDT (mechanical detection threshold). This test used von Frey monofilaments that were adapted to define tactile fibre thresholds.37 Twenty von Frey nylon monofilaments with different diameters were used and calibrated to exert specific forces when bending. Monofilament force varied from 0.008 g/mm2 to 300 g/mm2.37 Each monofilament was applied perpendicularly to the dentoalveolar region, and a slight pressure was made until the filament bent. The method of limits was used in which approximately 6–8 ascending/descending stimuli were applied, and the average force was calculated.38 MDT estimated the least von Frey nylon monofilament force that subjects were able to appropriately recognize.37 2.2.1.2. PDT (pain detection threshold). This test estimated the least von Frey filament force for which patients reported a painful sensation. The method of limits used in MDT was also applied for PDT. Patients identified the filament, and their pain intensity was recorded using VAS.20 2.2.1.3. DMA1 (dynamical mechanical allodynia with a cotton swab) and DMA2 (dynamical mechanical allodynia with a toothbrush). A slight vibration of a cotton swab (DMA1) and a soft toothbrush (DMA2) was applied to alveolar mucosa for 10 s for the study group only, and the pain intensity was recorded with VAS.20 The stimulus area was approximately 2 mm2 and 5 mm2 for the cotton swab and toothbrush, respectively. DMA is not detectable in healthy patients, so it was not tested on control group.
2.2.1.4. CPS (cold pain sensation) and HPS (heat pain sensation). A rod of aluminium (7-mm diameter) was placed in a container with ice at 0 8C (CPS) or hot water at 53 8C (HPS) for 1 min, and it was applied to the alveolar mucosa for approximately 4 s. Pain intensity was recorded using the VAS.39
2.2.1.5. WUR (wind-up ratio). This test was conducted using repeated application of the 5.46 g von Frey filament in a continuous 30-s sequence (force of 26 g/mm2, approximately one stimulus per second). Patients rated the pain intensity four times on an NRS (numeric rating scale) at the 1st second, 10th second, 20th second and 30th second. The NRS is a 0–10 point scale, and patients were asked to rate their pain from 0 to 10. A score of 0 indicates ‘‘no pain’’, and 10 is the ‘‘worst pain imaginable’’.40,41 WUR was determined using ratio calculations (painfulness of the first pinprick stimulation vs. painfulness of a train of 30th seconds of pinprick stimulations), and a single value was established. 2.2.2.
Data reduction and analysis
The ‘‘Z’’ score transformation was performed to standardize QST values and obtain a single value for each test for comparison with control subjects.22 (‘‘Z’’ score calculation = Xsingle patient Meancontrols/Standard Deviationcontrols). In the first analysis, the ‘‘X’’ value was used for the PDAP patient at baseline and the ‘‘controls’’ were healthy subjects. In the second analysis, the ‘‘X’’ value was used for the PDAP patients after anaesthesia and the ‘‘controls’’ were PDAP patients at baseline. QST values from each patient were transformed to ‘‘Z’’scores as described by Rolke et al.22 A score above 1.96 or below 1.96 fell outside the 95% confidence interval of the mean reference value, and these scores were considered sensory abnormalities. Abnormalities were subsequently categorized as a sensory gain or sensory loss. Statistical analysis was performed using the paired ‘‘t’’ test (after the Kolmogorov–Smirnov normality test) to verify significant differences between the PDAP site at baseline and after topical anaesthesia. The ‘‘t’’ test was used to identify differences between the PDAP and control groups. The results were considered significant at a level of 5%.
976
3.
archives of oral biology 60 (2015) 973–981
intensity increased after 30 s of repeated stimuli, and no differences were found in the ratios between 1st and 30th seconds for both groups (Table 2). Spontaneous pain at baseline dropped from 62.5 mm to 25.1 mm after topical anaesthetic gel application ( p < 0.001; CI = 2.671; 4.812). The topical anaesthesia showed approximately 60% reduction in pain intensity. Topical anaesthesia on QST increased the mechanical detection thresholds to tactile (MDT) and painful stimuli (PDT) and decreased the pain intensity reported for dynamic mechanical allodynia tests (DMA1 and DMA2) and the windup test (30 s of repeated stimuli) (Fig. 2). However, the pain intensity of hot and cold stimuli did not differ after topical anaesthesia (CPS and HPS) (Fig. 2). ‘‘Z’’ scores using ‘‘PDAP data at baseline’’ as case and ‘‘health subjects data’’ as control indicated a gain in function (positive ‘‘Z’’ score) in dynamic mechanical allodynia (DMA1 and DMA2) and heat and cold thermal tests (CPS and HPS) (Fig. 3). The other ‘‘Z’’ score comparison considered the ‘‘after anaesthesia data’’ as the case and ‘‘baseline data’’ as control in the PDAP group (Fig. 3). A gain in function after topical anaesthesia was observed for some patients in mechanical detection (MDT) and mechanical pain detection (PDT) threshold
Results
Patients with PDAP were mainly women (76%), with a mean age of 58.25 years (SD = 12.17) and mean pain duration of 42.33 months (range 09–120 months). The healthy controls were formed of 19 women and six men with a mean age of 58.92 (SD = 7.39). The most affected pain region was the mandibular region (64% of patients with PDAP, 16 mandible and nine maxilla). Eighty percent of the involved teeth were posterior and 60% were in the right side. This percentage was matched to the control group. In this study, 56% of PDAP patients had extracted teeth, and 44% had endodontic treatment (Table 1). Accordingly to Table 1, 80% of PDAP group presented psychosocial profiles consistent with depression features, 76% anxiety features and 80% with poor sleep quality, while 71.5% of healthy subjects had absent of depression features, 90.5% had no anxiety features and 58% had good sleep quality, evaluated through specific questionnaires. The mean results for QST are shown in Fig. 2 and Table 2. Patients with PDAP had lower pain detection thresholds (PDT) and higher pain intensity after heat and cold stimuli (HPS and CPS) than the controls. Wind-up data showed that pain
Table 1 – Sample characteristics of patients with PDAP. PDAP patient
Tooth
Pain intensity (on VAS)
Pain duration (on Months)
Depression features
Anxiety features
Poor sleep quality
Prior dentistry management
Drugs used per day
CBCT
1 2 3 4 5
34 45 16 38 11
23 48 24 36 57
24 24 120 36 12
Yes Yes Yes No Yes
No Yes Yes No Yes
Yes Yes Yes No Yes
Endodontics Endodontics Tooth extraction Tooth extraction Tooth extraction
No Yes Yes Yes Yes
6 7
21 38
94 100
7 18
Yes Yes
Yes No
Yes Yes
Tooth extraction Tooth extraction
8 9 10 11
45 36 32 24
71 96 54 72
18 36 6 72
Yes Yes Yes Yes
Yes Yes Yes Yes
No Yes Yes Yes
Tooth extraction Tooth extraction Tooth extraction Endodontics
12 13 14 15 16 17
34 46 44 46 15 36
83 83 100 49 51 90
48 36 60 90 72 36
No Yes Yes Yes No Yes
No Yes Yes Yes No Yes
No Yes Yes Yes No Yes
Endodontics Endodontics Endodontics Endodontics Endodontics Extraction
18 19 20 21 22 23 24 25
27 24 46 36 33 15 36 13
50 64 41 70 60 35 49 60
7 24 36 90 48 90 6 42
Yes Yes Yes No No Yes Yes Yes
Yes Yes Yes Yes No Yes Yes Yes
Yes Yes Yes No Yes Yes Yes Yes
Tooth extraction Tooth extraction Tooth extraction Tooth extraction Tooth extraction Endodontics Endodontics Endodontics
None None None None Amitriptyline 25 mg/Carbamazepin 50 mg/Gabapentin 300 mg) None Gabapentin 300 mg/Duloxetine 30 mg None Gabapentin 200 mg None Topiramate 25 mg/Alprazolam 1 mg None None None None Nimesulide 100 mg Gabapentin 200 mg/Carbamazepin 200 mg Carbamazepin 200 mg None Gabapentin 150 mg None None Sertraline 50 mg Gabapentin 600 mg Carbamazepin 400 mg
No Yes
Yes No No Yes
No No No Yes Yes No
Yes Yes No No No Yes No Yes
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archives of oral biology 60 (2015) 973–981
Fig. 2 – Mean values of QST in the PDAP group (at baseline and after topical anaesthesia) and the control group (at baseline). QST: quantitative sensory testing; MDT: mechanical detection threshold; PDT: pain detection threshold; DMA1: dynamic mechanical allodynia with a cotton swab and DMA2: with toothbrush; CPS: cold pain sensation; HPS: heat pain sensation; WUR: wind-up ratio; VAS: visual analogue scale; s: seconds; mm: millimetre; *p < 0.05.
Table 2 – Mean pain intensity (VAS) recorded in the first, 10th, 20th and 30th second and variation between the first second and 30th second for wind-up ratio (WUR). Group/time
PDAP at baseline PDAP after anaesthesia Control
1st(SD)
10th(SD)
20th(SD)
30th(SD)
Variation between 1st and 30th second
p (CI) between 1st and 30th
2.54 (1.99) 1.88 (2.34) 2.16 (1.97)
4.75 (2.64) 3.13 (2.93) 3.86 (2.29)
5.75 (2.62) 4.38 (3.28) 5.02 (2.4)
6.50 (2.96) 5.39 (3.45) 5.82 (2.70)
3.96 3.51 3.66
