Effect of topical anaesthesia in patients with persistent dentoalveolar pain disorders: A quantitative sensory testing evaluation

archives of oral biology 60 (2015) 973–981

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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.

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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.

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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%.

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3.

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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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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

<0.01 ( 4.710; 3.206) <0.01 ( 4.176; 2.407) <0.01 ( 4.553; 2.767)

CI: confidence interval; SD: standard deviation.

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Fig. 3 – (A) ‘‘Z’’ score sensory profiles of patients with PDAP at baseline when healthy subjects’ values were used as control. (B) ‘‘Z’’ score sensory profiles of patients with PDAP after topical anaesthesia when PDAP values at baseline were used as control. 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.

tests. One patient had a gain in function in dynamic mechanical allodynia with toothbrush (DMA1), and two patients had a gain in function in heat tests (HPS) (Fig. 3).

4.

Discussion

The results of this QST study using topical application of an anaesthetic gel indicated the following results. 1)The first hypothesis was accepted: patients with PDAP had somatosensory abnormalities of lower pain detection thresholds and higher pain intensity reports of thermal stimuli (heat and cold) than healthy subjects. 2)The presence of dynamic allodynia was observed in the PDAP group. 3)The second hypothesis was rejected: topical anaesthesia partially reduced pain intensity in patients with PDAP. 4)Anaesthetic gel increased the mechanical detection thresholds and reduced the pain intensity report in dynamic mechanical allodynia tests. A total of 76% of our sample were women with a mean age of 58 years. These data are consistent with epidemiological studies of the age and gender characteristics of PDAP.13,16,42,43 Most patients were taking pain medications,

such as anticonvulsants (nine patients), antidepressants (two patients) and/or anxiolytics (one patient), which are understandable based on the chronic, refractory nature of such a disturbance. This fact did not influence the initial pain severity (61 mm). In a similar study, the levels of pain of atypical odontalgia patients were not statistically significant regardless of neuropathic pain medication status.14 In this study, hypertension patients were excluded based on both human and animal studies had demonstrated functional interactions between cardiovascular and pain regulatory systems.25,44,45 According to these studies high resting blood pressures was consistently associated with reduced pain sensitivity, suggesting an inverse relationship between blood pressure and pain sensitivity across the whole blood pressure spectrum.25,44,45 Numerous psychosocial comorbidities, such as depression, anxiety and poor sleep quality are associated to chronic orofacial pain.46,47 Based on this, results of QST may be altered by the psychological state and the psychosocial evaluation of patients must be addressed as part of individual’s anamnesis. In addiction, somatosensory abnormalities are common in patients with PDAP, and QSTs are appropriate tools to evaluate

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these cases.13,48 However, even though QST might help to discriminate between patients (PDAP and healthy subjects), studies have demonstrated that the ability of QSTs to predict the severity of psychosocial disability in patients still seems limited.49 The mechanical detection thresholds in PDAP patients were not different from those of controls in this study, which suggests that somatosensory changes in tactile fibres did not occur in these patients. Pain detection threshold (PDT) findings suggested that patients with PDAP have heightened pain sensitivity because the strength of the application of a mechanical stimulus was perceived as strong enough to produce a higher intensity pain sensation. This study showed a decreased PDT in the PDAP group. These results are similar to previous studies that evaluated somatosensory abnormalities in atypical odontalgia.13,14,42 The Neuropathic Pain Research Consortium warns that this sensory alteration can prove the presence of hyperalgesia as evaluated using PDT.50 Allodynia is also common in neuropathic disorders.12,51 Allodynia reflects the presence of central sensitization in patients with PDAP; therefore, peripheral nerve impulses alone do not explain the persistent pain in these patients.16,52 The use of dynamic mechanical allodynia testing is easily implemented. A professional in clinical settings may perform this test using only the vibrating bristles of a toothbrush or cotton swab in the region where the patient reports pain, and the patient will perceive a pain increase after this stimulus.53 The PDAP group was more sensitive to thermal pain detection tests in this study. This result is compatible with peripheral sensitization and a sensory gain in PDAP patients. This fact likely indicates that thermal stimulation increases ectopic nerve impulse transmission from the periphery to the cerebral cortex in PDAP patients.50 Heat pain sensation also suggests central sensitization and temporal summation, a process that is related to the constant and repeated stimulation of C fibre nociceptors, which results in exaggerated and amplified stimuli to the trigeminal system.50 Increased neuronal activity following repetitive stimulation is the clinical equivalent to wind-up-like pain or abnormal temporal summation. WUR measures these features, and no differences were found in this study. These data contrast the results of another study.13 It is suggested that WUR may not be the standard protocol for clinical evaluations to assess central sensitization and temporal summation processes in PDAP patients. Dynamic allodynia tests seem to more reliably predict these central sensitization processes. This study presented new data for the use of a topical anaesthetic gel to investigate peripheral involvement in intraoral neuropathic pain patients. These pain fibres in a neuropathic condition become hyperexcitable, which increases pain and aids our understanding that peripheral neurogenic inflammation may be present.1,43 While it is clear that topical anaesthesia has effects on PDAP patients, it is hard to speculate about the completeness of topical cream on neural fibres. Mechanical detection thresholds were increased after anaesthesia, which shows that blockade of peripheral fibres likely involves the blocking of tactile fibres such as Abeta fibre.54 Previous studies have demonstrated that A-delta fibre blockade did not decrease mechanical hyperalgesia in neuropathic pain patients, which demonstrates the role of

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non-myelinated C fibres.55 Hyperalgesia detected by pain threshold tests are decreased after topical anaesthesia in this study group, which may involve a partial C fibre blockade by the anaesthetic gel in these patients.54 However, partial effects of anaesthesia on A-delta fibres also may be involved on the reduction of pain sensation, but these inferences could not be done because of limitation with the absence of topical application of anaesthesia on normal pain-free subjects. Nerve fibre blockade by anaesthetic gel could not hinder all fibres involved in PDAP pathogenesis or other features, such as pain modulation disorders, central sensitization, psychosocial and genetic factors that are also involved in PDAP patients.51 Further studies of PDAP pathophysiology are needed to understand this painful condition and the role of peripheral pain conduction. It is important to note that topical anaesthesia is absorbed only at the applied site, and it typically affects local peripheral tissues with no systemic uptake.56 Topical anaesthesia knocks down nociceptor discharge at the level of the peripheral dentoalveolar mucosa, and light mechanical stimulation evokes feelings of touch but not pain.57 This result is one possible explanation for the reduced pain intensity after topical anaesthesia in dynamic allodynia tests and likely indicates that the reduction of peripheral impulses leads to a reduction in central excitatory effects, such as allodynia.58 Furthermore, ‘‘Z’’-score analysis is used to examine individual patients and to investigate their data within the normal range for each QST parameter. This study indicated a sensory gain (positive ‘‘Z’’ scores) in dynamic mechanical allodynia and hot and cold thermal tests. Thermal pain sensation may suggest central sensitization and temporal summation, and it was estimated that some PDAP patients had positive ‘‘Z’’ scores because of their chronic neuropathy.50 Another study analyzed ‘‘Z’’ scores for some QSTs in three neuropathic patients and reported different patterns of somatosensory abnormalities, with positive and negative values in the same tests.13 This variability in QST patterns may be an indication that different features of afferent nerve fibres are involved in the development and maintenance of chronic neuropathic pain, with connections between peripheral and central mechanisms.13 The ‘‘Z’’ score is a simplistic analysis, and these values differ greatly between subjects. The present investigation was the first study to calculate ‘‘Z’’ score transformations before and after anaesthesia, and a gain in function through mechanical detection tests after topical anaesthesia was observed. This result could predict that tactile fibre block using anaesthesia can increase the mechanical detection threshold for PDAP patients. Moreover, some QST limitations may be noted: 1)the time taken to perform the tests in all areas could enable the patients to become fatigued; 2)mechanical stimulation tests confuse some patients because they use 6–8 negative and positive responses, especially where a longer explanation and repeated testing was required; 3)controls did not have the topical application of local anaesthetic and repeated QST examination and 4)the effect of local anaesthetic was not controlled with the use of a placebo in this study, and these results should be analyzed with caution. Further studies using placebo are encouraged. This study suggests that PDAP patients have somatosensory abnormalities that are consistent with peripheral and

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central sensitization. Thermal sensory gain and the presence of dynamic mechanical allodynia indicated central sensitization. Conversely, a topical anaesthetic significantly reduced pain intensity, and increased mechanical and pain detection thresholds, which suggests a peripheral disorder.

Contributors Conception and design: Andre´ Luı´s Porporatti, Yuri Martins Costa, Juliana Stuginski-Barbosa, Paulo Ce´sar Rodrigues Conti. ´ s Porporatti, Juliana Stuginski˜ LuU Acquisition of dataAndrO Barbosa, Leonardo Rigoldi Bonjardim. Yuri Martins Costa Analysis and interpretation of data: Andre´ Luı´s Porporatti, Paulo Ce´sar Rodrigues Conti, Juliana Stuginski-Barbosa, Leonardo Rigoldi Bonjardim. Drafting the manuscript: Andre´ Luı´s Porporatti, Yuri Martins Costa, Juliana Stuginski-Barbosa. Revising for intellectual content: Leonardo Rigoldi Bonjardim, Paulo Ce´sar Rodrigues Conti. ´ s Porpor˜ LuU Final approval and completed manuscriptAndrO atti, Yuri Martins Costa, Juliana Stuginski-Barbosa, Leonardo ˜ sar Rodrigues Conti. Rigoldi Bonjardim, Paulo CO

Funding This work was supported by the Sa˜o Paulo Research Foundation – FAPESP (Number 2011/14915-5).

Competing interests There were no conflicts of interest in the performance of this study.

Ethical approval Ethical approval was given by Academic Investigation Review Board from Bauru School of Dentistry, University of Sa˜o Paulo (Protocol 081/2011).

references

1. Nixdorf DR, Drangsholt MT, Ettlin DA, Gaul C, De Leeuw R, Svensson P, et al. Classifying orofacial pains: a new proposal of taxonomy based on ontology. J Oral Rehabil 2012;39(3):161–9. 2. Melis M, Lobo SL, Ceneviz C, Zawawi K, Al-Badawi E, Maloney G, et al. Atypical odontalgia: a review of the literature. Headache 2003;43(10):1060–74. 3. Woda A, Pionchon P. A unified concept of idiopathic orofacial pain: clinical features. J Orofac Pain 1999;13(3): 172–84. [discussion 185-195]. 4. Headache Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia 1988;8(Suppl. 7):1–96. 5. Campbell RL, Parks KW, Dodds RN. Chronic facial pain associated with endodontic therapy. Oral Surg Oral Med Oral Pathol 1990;69(3):287–90.

6. Marbach JJ, Hulbrock J, Hohn C, Segal AG. Incidence of phantom tooth pain: an atypical facial neuralgia. Oral Surg Oral Med Oral Pathol 1982;53(2):190–3. 7. Vickers ER, Cousins MJ, Walker S, Chisholm K. Analysis of 50 patients with atypical odontalgia. A preliminary report on pharmacological procedures for diagnosis and treatment. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;85(1): 24–32. 8. Marbach JJ. Is phantom tooth pain a deafferentation (neuropathic) syndrome? Part II. Psychosocial considerations. Oral Surg Oral Med Oral Pathol 1993;75(2):225–32. 9. Marbach JJ. Is phantom tooth pain a deafferentation (neuropathic) syndrome? Part I. Evidence derived from pathophysiology and treatment. Oral Surg Oral Med Oral Pathol 1993;75(1):95–105. 10. Matwychuk MJ. Diagnostic challenges of neuropathic tooth pain. J Can Dent Assoc 2004;70(8):542–6. 11. Melis M, Secci S. Diagnosis and treatment of atypical odontalgia: a review of the literature and two case reports. J Contemp Dent Pract 2007;8(3):81–9. 12. Baad-Hansen L. Atypical odontalgia – pathophysiology and clinical management. J Oral Rehabil 2008;35(1):1–11. 13. List T, Leijon G, Svensson P. Somatosensory abnormalities in atypical odontalgia: a case–control study. Pain 2008;139(2):333–41. 14. Zagury JG, Eliav E, Heir GM, Nasri-Heir C, Ananthan S, Pertes R, et al. Prolonged gingival cold allodynia: a novel finding in patients with atypical odontalgia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;111(3):312–9. 15. Graff-Radford SB, Solberg WK. Atypical odontalgia. J Craniomandib Disord 1992;6(4):260–5. 16. List T, Leijon G, Helkimo M, Oster A, Svensson P. Effect of local anesthesia on atypical odontalgia – a randomized controlled trial. Pain 2006;122(3):306–14. 17. Devor M, Wall PD, Catalan N. Systemic lidocaine silences ectopic neuroma and DRG discharge without blocking nerve conduction. Pain 1992;48(2):261–8. 18. Campbell JN, Meyer RA. Mechanisms of neuropathic pain. Neuron 2006;52(1):77–92. 19. Pigg M, Baad-Hansen L, Svensson P, Drangsholt M, List T. Reliability of intraoral quantitative sensory testing (QST). Pain 2010;148(2):220–6. 20. Svensson P, Baad-Hansen L, Pigg M, List T, Eliav E, Ettlin D, et al. Guidelines and recommendations for assessment of somatosensory function in oro-facial pain conditions – a taskforce report. J Oral Rehabil 2011;38(5):366–94. 21. Rolke R, Magerl W, Campbell KA, Schalber C, Caspari S, Birklein F, et al. Quantitative sensory testing: a comprehensive protocol for clinical trials. Eur J Pain 2006;10(1):77–88. 22. Rolke R, Baron R, Maier C, Tolle TR, Treede RD, Beyer A, et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values. Pain 2006;123(3):231–43. 23. Pigg M, List T, Petersson K, Lindh C, Petersson A. Diagnostic yield of conventional radiographic and cone-beam computed tomographic images in patients with atypical odontalgia. Int Endod J 2011;44(12):1092–101. 24. Pickering TG. Effects of stress and behavioral interventions in hypertension. Pain and blood pressure. J Clin Hypertens (Greenwich) 2003;5(5):359–61. 25. Bruehl S, Chung OY. Interactions between the cardiovascular and pain regulatory systems: an updated review of mechanisms and possible alterations in chronic pain. Neurosci Biobehav Rev 2004;28(4):395–414. 26. Creamer M, Foran J, Bell R. The Beck Anxiety Inventory in a non-clinical sample. Behav Res Ther 1995;33(4):477–85. 27. Gorenstein C, Andrade L. Validation of a Portuguese version of the Beck Depression Inventory and the State-Trait

archives of oral biology 60 (2015) 973–981

28.

29.

30. 31.

32.

33.

34. 35.

36. 37.

38.

39.

40.

41.

42.

Anxiety Inventory in Brazilian subjects. Braz J Med Biol Res 1996;29(4):453–7. Palmer GA, Happe MC, Paxson JM, Jurek BK, Graca JJ, Olson SA. Psychometric properties of the Beck Depression Inventory-II for OEF/OIF veterans in a polytrauma sample. Military Med 2014;179(8):879–84. Subica AM, Fowler JC, Elhai JD, Frueh BC, Sharp C, Kelly EL, et al. Factor structure and diagnostic validity of the Beck Depression Inventory-II with adult clinical inpatients: comparison to a gold-standard diagnostic interview. Psychol Assess 2014. Beck A. The Beck anxiety inventory manual. Harcourt Brace; 1961. Buysse DJ, Reynolds 3rd CF, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 1989;28(2):193–213. Hancock P, Larner AJ. Diagnostic utility of the Pittsburgh Sleep Quality Index in memory clinics. Int J Geriatr Psychiatry 2009;24(11):1237–40. Bertolazi AN, Fagondes SC, Hoff LS, Dartora EG, Miozzo IC, de Barba ME, et al. Validation of the Brazilian Portuguese version of the Pittsburgh Sleep Quality Index. Sleep Med 2011;12(1):70–5. Rocha APCea. Dor: Aspectos Atuais da Sensibilizac¸a˜o Perife´rica e Central. Rev Bras Anestesiol 2007;57(1):94–105. Lu S, Baad-Hansen L, List T, Zhang Z, Svensson P. Somatosensory profiling of intra-oral capsaicin and menthol in healthy subjects. Eur J Oral Sci 2013;121(1): 29–35. Ferreira-Valente MA, Pais-Ribeiro JL, Jensen MP. Validity of four pain intensity rating scales. Pain 2011;152(10):2399–400. Levin S, Pearsall G, Ruderman RJ. Von Frey’s method of measuring pressure sensibility in the hand: an engineering analysis of the Weinstein-Semmes pressure aesthesiometer. J Hand Surg Am 1978;3(3):211–6. Hansson P, Backonja M, Bouhassira D. Usefulness and limitations of quantitative sensory testing: clinical and research application in neuropathic pain states. Pain 2007;129(3):256–9. Lee YS, Kho HS, Kim YK, Chung SC. Influence of topical capsaicin on facial sensitivity in response to experimental pain. J Oral Rehabil 2007;34(1):9–14. Brunelli C, Zecca E, Martini C, Campa T, Fagnoni E, Bagnasco M, et al. Comparison of numerical and verbal rating scales to measure pain exacerbations in patients with chronic cancer pain. Health Qual Life Outcomes 2010;8:42. Dworkin RH, Turk DC, Farrar JT, Haythornthwaite JA, Jensen MP, Katz NP, et al. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain 2005;113(1–2):9–19. Baad-Hansen L, Juhl GI, Jensen TS, Brandsborg B, Svensson P. Differential effect of intravenous S-ketamine and

43.

44.

45.

46. 47.

48.

49.

50.

51.

52.

53.

54. 55.

56.

57. 58.

981

fentanyl on atypical odontalgia and capsaicin-evoked pain. Pain 2007;129(1–2):46–54. Baad-Hansen L, List T, Jensen TS, Svensson P. Increased pain sensitivity to intraoral capsaicin in patients with atypical odontalgia. J Orofac Pain 2006;20(2):107–14. Chung OY, Bruehl S, Diedrich L, Diedrich A. The impact of blood pressure and baroreflex sensitivity on wind-up. Anesth Analg 2008;107(3):1018–25. Ghione S. Hypertension-associated hypalgesia. Evidence in experimental animals and humans, pathophysiological mechanisms, and potential clinical consequences. Hypertension 1996;28(3):494–504. Zakrzewska JM. Multi-dimensionality of chronic pain of the oral cavity and face. J Headache Pain 2013;14(1):37. Gerrits MM, Vogelzangs N, van Oppen P, van Marwijk HW, van der Horst H, Penninx BW. Impact of pain on the course of depressive and anxiety disorders. Pain 2012;153(2):429–36. Cruccu G, Anand P, Attal N, Garcia-Larrea L, Haanpaa M, Jorum E, et al. EFNS guidelines on neuropathic pain assessment. Eur J Neurol 2004;11(3):153–62. Hubscher M, Moloney N, Leaver A, Rebbeck T, McAuley JH, Refshauge KM. Relationship between quantitative sensory testing and pain or disability in people with spinal pain-a systematic review and meta-analysis. Pain 2013;154(9): 1497–504. Walk D, Sehgal N, Moeller-Bertram T, Edwards RR, Wasan A, Wallace M, et al. Quantitative sensory testing and mapping: a review of nonautomated quantitative methods for examination of the patient with neuropathic pain. Clin J Pain 2009;25(7):632–40. Leeuw Rd. Orofacial pain: guidelines for assessment, diagnosis, and management. 4th ed. Quintessence: American Academy of Orofacial Pain; 2008. Woolf CJ, Mannion RJ. Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet 1999;353(9168):1959–64. Baad-Hansen L, Pigg M, Ivanovic SE, Faris H, List T, Drangsholt M, et al. Intraoral somatosensory abnormalities in patients with atypical odontalgia-a controlled multicenter quantitative sensory testing study. Pain 2013. Yagiela JA. Local anesthetics. Anesthesia Prog 1991;38 (4–5):128–41. Ochoa JL, Yarnitsky D. Mechanical hyperalgesias in neuropathic pain patients: dynamic and static subtypes. Ann Neurol 1993;33(5):465–72. Nasri-Heir C, Khan J, Heir GM. Topical medications as treatment of neuropathic orofacial pain. Dent Clin North Am 2013;57(3):541–53. Campbell JN. How does topical lidocaine relieve pain? Pain 2012;2(153):255–6. Gracely RH, Lynch SA, Bennett GJ. Painful neuropathy: altered central processing maintained dynamically by peripheral input. Pain 1992;51(2):175–94.