Somatosensory Investigation of Patients With Orofacial Pain Compared With Controls Silvia R.D.T. de Siqueira, D.D.S., Ph.D. Manoel J. Teixeira, M.D., Ph.D. Jose T. T. de Siqueira, D.D.S., Ph.D. The objective of this study was to investigate the sensorial characteristics of orofacial pain in patients compared with control subjects. A total of 336 subjects (282 patients and 54 control subjects) were evaluated to identify their thermal (cold and warm), tactile, and pain thresholds. Numbness was reported by 61.7% of the patients (p,0.001). Patients with trigeminal postherpetic neuralgia and burning mouth syndrome showed loss of thermal perception; patients with postherpetic neuralgia, burning mouth syndrome, and posttraumatic painful neuropathy had a decrease in tactile perception compared with the control subjects (p,0.001). In conclusion, other sensorial modalities besides pain are affected by neuropathic orofacial pain; these findings can help in the understanding of the pathophysiological mechanisms in orofacial pain. (The Journal of Neuropsychiatry and Clinical Neurosciences 2014; 26:376–381)
T
he motor findings of several conditions have been extensively studied during the last century. However, it was only in the last few decades that clinical methodologies with precise equipment were developed and used in neurological and nonneurological diseases with the aim of clarification of pathophysiological mechanisms underlying these processes.1–4 Pain is one somatosensory modality, and thus sensory findings are important to be elucidated, and among orofacial conditions, special modalities such as gustation and olfaction have been considered.5–14 Among orofacial syndromes, there is evidence of sensory impairment in patients with idiopathic trigeminal neuralgia,15,16 burning mouth syndrome,17 trigeminal postherpetic neuralgia, 18 atypical odontalgia, 19 atypical facial pain,20 persistent idiopathic facial pain,21 and temporomandibular disorders22,23 and patients that underwent surgical oral procedures (third molar extractions, orthognatic surgeries),24,25 but these findings are not clearly understood. Thus, the objective of this study was to investigate the sensorial characteristics of orofacial pain in patients compared with control subjects.
METHODS Subjects We enrolled 282 consecutive patients with orofacial pain who had been diagnosed at the Orofacial Pain Clinic of Received March 27, 2013; revised March 27 and May 14, 2013; accepted May 16, 2013. From the School of Arts, Science and Humanities (SRDTdS); Neurology Department, School of Medicine (MJT); and Dentistry Division, Hospital das Clinicas, School of Medicine (JTTdS), University of Sao Paulo, Sao Paulo, Brazil. Send correspondence to Silvia R.D.T. de Siqueira, D.D.S., Ph.D.; e-mail: silviadowgan@hotmail. com Copyright © 2014 American Psychiatric Association
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J Neuropsychiatry Clin Neurosci 26:4, Fall 2014
DE SIQUEIRA et al. the Hospital das Clinicas of the School of Medicine, University of Sao Paulo. The patients had been recently diagnosed by the clinic. They were referred to the clinic between March 2003 and March 2009. They were 176 (62.4%) women, and the mean age was 58.20613.56 years old (mean 6 standard deviation). In the control group, we included 54 healthy subjects who had no orofacial pain complaints. There were 30 (55.6%) women, and their mean age was 45.67615.08 years old (mean 6 standard deviation). Inclusion criterion for the study group was orofacial pain complaint for more than 6 months. The orofacial pain was diagnosed according to the criteria of the International Association for the Study of Pain.26 Eight patients had fibromyalgia associated with their facial pain, and they had been diagnosed according to the criteria of the American College of Rheumatology.27 The healthy subjects of the control group did not had any orofacial or generalized pain complaints before or at the time of the evaluation. Exclusion criteria for both groups were systemic medical conditions (except fibromyalgia syndrome and diabetes mellitus in the study group) (e.g., other chronic pain syndromes and neurological or other rheumatological conditions). All patients and control subjects were informed about the purposes of the study, and all signed informed consent. The protocol was approved by the local Ethics Committee. Demographic data were compared using Pearson’s chi-square test (SPSS 17.0; SPSS, Chicago). There were no differences in ages or sex between the groups (p.0.50). The patients that had burning mouth syndrome, posttraumatic neuropathy, cervicogenic headache, temporomandibular disorders, and persistent idiopathic facial pain did not take any medication within the last 6 months before the evaluation. Sporadic use of anti-inflammatory drugs and analgesics was reported by all patients (automedication), and the most commonly reported were dipyrone and acetaminophen. The patients with diabetic neuropathy were only taking hypoglycemics (metiformin and glibenclamide), the patients with idiopathic trigeminal neuralgia were taking carbamazepine (40021200 mg daily), and the patients with postherpetic neuralgia and fibromyalgia were taking amitryptiline (252150 mg daily). They had been taking the medications for at least 6 months prior to the study with no variation in doses. At the time of the study, none of the control subjects were taking analgesic medications; this is also true for the 6 months before the evaluation.28
J Neuropsychiatry Clin Neurosci 26:4, Fall 2014
TABLE 1.
Orofacial Pain Diagnoses and Laterality in the Study Group (N=282)
Diagnoses and laterality
N (%)
Diagnoses Idiopathic trigeminal neuralgia Persistent idiopathic facial pain Trigeminal diabetic neuropathy Trigeminal posttraumatic neuropathy Trigeminal postherpetic neuralgia Burning mouth syndrome Temporomandibular disorders Fibromyalgia Cervicogenic headache Laterality Right Left Bilateral
162 (57.4) 30 (10.6) 30 (10.6) 19 (6.7) 18 (6.4) 11 (3.9) 5 (1.8) 5 (1.8) 2 (0.7) 139 (49.3) 89 (31.6) 54 (19.1)
Subjective Sensory Investigation All subjects were interviewed about their perception of sensorial abnormalities, such as numbness and dysesthesia. The frequency of sensorial abnormalities (absent, eventual, frequent, or constant) and the intensity of the sensation (0–10 by the visual analog scale) were evaluated. Quantitative Sensory Testing All subjects underwent a standardized protocol of superficial facial perception, which was applied to distinct areas of the face (bilateral trigeminal branches)14,15: 1) thermal perception—cold and warm perception (electrical device designed at the Functional Neurosurgery Division, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo); 2) mechanical/tactile perception—microfilaments of von Frey; and 3) pain perception—superficial algometry (Micromar, Diadema, São Paulo, Brazil). Each thermal and mechanical stimulus was applied three times, and the threshold was identified when the subject recognized at least two of the three applications; if not, the next stimulus in a crescent order (starting with the smaller concentration) would be applied to avoid a tolerance effect. The algometry was performed with a superficial device and a disposable needle of 0.7315 mm. The somatosensory testing was performed at the three trigeminal branches (ophthalmic: front 22 cm above the pupil; maxillary: cheek 21 cm lateral to the nose wing; mandibular: chin skin 21 cm below the lip angle).15,18 The evaluation was performed in a silent room with acoustic protection and the doors closed. The subjects were sitting with their heads resting on a flat surface in the position with the Frankfurt line parallel to the floor. Only the patient and the researcher were in the room. All
http://neuro.psychiatryonline.org
377
SOMATOSENSORY FACIAL ASPECTS
TABLE 2.
Distribution of Age, Sex, Side, and Branch Affected According to the Diagnosis (N=282) Sex (%)
Side affected (%)
ITN (N=162)
60.51611.91 (34–85)
Age (years)
88 (54.3) women
101 (62.3) right 60 (37) left 01 (0.6) bilateral
TMD (N=5)
47.5066.84 (41–56)
5 (100) women
BMS (N=11) PIFP (N=30)
54.2568.63 (35–61) 43.80617.46 (23–76)
11 (100) women 29 (96.7) women
Fibromyalgia (N=5) PHN (N=18)
43.50612.02 (35–52) 71.3368.16 (55–82)
4 (80) women 12 (66.7) women
3 (60) right 2 (40) left 11 (100) bilateral 14 (46.7) right 10 (33.3) left 6 (20) bilateral 5 (100) bilateral 14 (77.8) right 4 (22.2) left
PTN (N=19)
47.94614.74 (32–83)
14 (73.7) women
CH (N=2) DN (N=30) p valuea
40.0060.00 (40) 57.6769.26 (37–77) 0.020
1 (50) woman 12 (40) women ,0.001
5 (26.3) right 13 (68.4) left 1 (5.3) bilateral 2 (100) right 30 (100) bilateral ,0.001
Branch affected (%) 6 50 44 14 40 7 1
(3.7) V1 (30.9) V2 (27.2) V3 (8.6) V1–2 (24.7) V2–3 (4.3) V1–2–3 (0.6) V1–3 — — —
12 2 1 2 1
— (66.7) V1 (11.1) V2 (5.6) V1–2 (11.1) V2–3 (5.6) V1–2–3 — — — ,0.001
BMS: burning mouth syndrome; CH: cervicogenic headache; DN: diabetic neuropathy; ITN: idiopathic trigeminal neuralgia; PHN: trigeminal postherpetic neuralgia; PIFP: persistent idiopathic facial pain; PTN: posttraumatic neuralgia; TMD: temporomandibular disorder; V1: ophthalmic branch; V2: maxillary branch; V3: mandibular branch; V1–2: ophthalmic and maxillary branches; V2–3: maxillary and mandibular branches; V1–2– 3: ophthalmic, maxillary, and mandibular branches; V1–3: ophthalmic and mandibular braches. a One-way analysis of variance, chi-square and Fisher’s exact tests.
patients were evaluated by the same researcher. The patients and control subjects received the same instructions after they were positioned, which were to keep the eyes closed during the exam and that stimulus would be applied at their face and mouth and they should identify TABLE 3.
Numbness and Dysesthesia According to the Diagnosis (N=336)
ITN (N=162) TMD (N=5) BMS (N=11) PIFP (N=30) Fibromyalgia (N=5) PHN (N=18) PTN (N=19) CH (N=2) DN (N=30) Controls (N=54) p valuea
Numbness [N (%)]
Dysesthesia [N (%)]
106 (65.4) 3 (60) 5 (45.5) 15 (50) 3 (60) 16 (88.9) 17 (89.5) 2 (100) 7 (23.3) 5 (9.3) ,0.001
29 (17.9) 3 (60) 5 (45.5) 12 (40) 3 (60) 15 (83.3) 16 (84.2) 0 (0) 4 (13.3) 5 (9.3) ,0.001
BMS: burning mouth syndrome; CH: cervicogenic headache; DN: diabetic neuropathy; ITN: idiopathic trigeminal neuralgia; PHN: trigeminal postherpetic neuralgia; PIFP: persistent idiopathic facial pain; PTN: posttraumatic neuralgia; TMD: temporomandibular disorder. a Chi-square and Fisher’s exact tests.
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and report if they felt it and what they felt (by saying “yes” or “no” and “which was the stimulus”). Only the researcher knew the order of the stimuli. Finally, all findings were tabled and statistically analyzed. 1. Thermal perception. Thermal (cold and warm) tests were performed with the equipment Thermosensi II (Functional Neurosurgery Division, Psychiatry Institute, Hospital das Clinicas, Medical School of the University of São Paulo, Sao Paulo, Brazil). The baseline temperature was 32°C, and the contact area of the thermode was 10310 mm. The stimuli were applied with an amplitude of 0–45°C; the equipment has a temperature change speed of 1°C/sec. 2. Mechanical tactile detection. Tactile tests were performed with standardized von Frey filaments with rounded tips of 0.5 mm of diameter (IITC, Woodland Hills, Calif.) (unit: g/mm2). 3. Pain detection (superficial algometry). Pain thresholds were evaluated at the skin surface with needles of 3030.7 mm perpendicularly applied with a mechanical algometer (Micromar, Diadema, Brazil). (unit: g/mm 2).
J Neuropsychiatry Clin Neurosci 26:4, Fall 2014
DE SIQUEIRA et al.
FIGURE 1.
Impairment of Thermal Detections
A. Cold (p
T
he motor findings of several conditions have been extensively studied during the last century. However, it was only in the last few decades that clinical methodologies with precise equipment were developed and used in neurological and nonneurological diseases with the aim of clarification of pathophysiological mechanisms underlying these processes.1–4 Pain is one somatosensory modality, and thus sensory findings are important to be elucidated, and among orofacial conditions, special modalities such as gustation and olfaction have been considered.5–14 Among orofacial syndromes, there is evidence of sensory impairment in patients with idiopathic trigeminal neuralgia,15,16 burning mouth syndrome,17 trigeminal postherpetic neuralgia, 18 atypical odontalgia, 19 atypical facial pain,20 persistent idiopathic facial pain,21 and temporomandibular disorders22,23 and patients that underwent surgical oral procedures (third molar extractions, orthognatic surgeries),24,25 but these findings are not clearly understood. Thus, the objective of this study was to investigate the sensorial characteristics of orofacial pain in patients compared with control subjects.
METHODS Subjects We enrolled 282 consecutive patients with orofacial pain who had been diagnosed at the Orofacial Pain Clinic of Received March 27, 2013; revised March 27 and May 14, 2013; accepted May 16, 2013. From the School of Arts, Science and Humanities (SRDTdS); Neurology Department, School of Medicine (MJT); and Dentistry Division, Hospital das Clinicas, School of Medicine (JTTdS), University of Sao Paulo, Sao Paulo, Brazil. Send correspondence to Silvia R.D.T. de Siqueira, D.D.S., Ph.D.; e-mail: silviadowgan@hotmail. com Copyright © 2014 American Psychiatric Association
376
http://neuro.psychiatryonline.org
J Neuropsychiatry Clin Neurosci 26:4, Fall 2014
DE SIQUEIRA et al. the Hospital das Clinicas of the School of Medicine, University of Sao Paulo. The patients had been recently diagnosed by the clinic. They were referred to the clinic between March 2003 and March 2009. They were 176 (62.4%) women, and the mean age was 58.20613.56 years old (mean 6 standard deviation). In the control group, we included 54 healthy subjects who had no orofacial pain complaints. There were 30 (55.6%) women, and their mean age was 45.67615.08 years old (mean 6 standard deviation). Inclusion criterion for the study group was orofacial pain complaint for more than 6 months. The orofacial pain was diagnosed according to the criteria of the International Association for the Study of Pain.26 Eight patients had fibromyalgia associated with their facial pain, and they had been diagnosed according to the criteria of the American College of Rheumatology.27 The healthy subjects of the control group did not had any orofacial or generalized pain complaints before or at the time of the evaluation. Exclusion criteria for both groups were systemic medical conditions (except fibromyalgia syndrome and diabetes mellitus in the study group) (e.g., other chronic pain syndromes and neurological or other rheumatological conditions). All patients and control subjects were informed about the purposes of the study, and all signed informed consent. The protocol was approved by the local Ethics Committee. Demographic data were compared using Pearson’s chi-square test (SPSS 17.0; SPSS, Chicago). There were no differences in ages or sex between the groups (p.0.50). The patients that had burning mouth syndrome, posttraumatic neuropathy, cervicogenic headache, temporomandibular disorders, and persistent idiopathic facial pain did not take any medication within the last 6 months before the evaluation. Sporadic use of anti-inflammatory drugs and analgesics was reported by all patients (automedication), and the most commonly reported were dipyrone and acetaminophen. The patients with diabetic neuropathy were only taking hypoglycemics (metiformin and glibenclamide), the patients with idiopathic trigeminal neuralgia were taking carbamazepine (40021200 mg daily), and the patients with postherpetic neuralgia and fibromyalgia were taking amitryptiline (252150 mg daily). They had been taking the medications for at least 6 months prior to the study with no variation in doses. At the time of the study, none of the control subjects were taking analgesic medications; this is also true for the 6 months before the evaluation.28
J Neuropsychiatry Clin Neurosci 26:4, Fall 2014
TABLE 1.
Orofacial Pain Diagnoses and Laterality in the Study Group (N=282)
Diagnoses and laterality
N (%)
Diagnoses Idiopathic trigeminal neuralgia Persistent idiopathic facial pain Trigeminal diabetic neuropathy Trigeminal posttraumatic neuropathy Trigeminal postherpetic neuralgia Burning mouth syndrome Temporomandibular disorders Fibromyalgia Cervicogenic headache Laterality Right Left Bilateral
162 (57.4) 30 (10.6) 30 (10.6) 19 (6.7) 18 (6.4) 11 (3.9) 5 (1.8) 5 (1.8) 2 (0.7) 139 (49.3) 89 (31.6) 54 (19.1)
Subjective Sensory Investigation All subjects were interviewed about their perception of sensorial abnormalities, such as numbness and dysesthesia. The frequency of sensorial abnormalities (absent, eventual, frequent, or constant) and the intensity of the sensation (0–10 by the visual analog scale) were evaluated. Quantitative Sensory Testing All subjects underwent a standardized protocol of superficial facial perception, which was applied to distinct areas of the face (bilateral trigeminal branches)14,15: 1) thermal perception—cold and warm perception (electrical device designed at the Functional Neurosurgery Division, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo); 2) mechanical/tactile perception—microfilaments of von Frey; and 3) pain perception—superficial algometry (Micromar, Diadema, São Paulo, Brazil). Each thermal and mechanical stimulus was applied three times, and the threshold was identified when the subject recognized at least two of the three applications; if not, the next stimulus in a crescent order (starting with the smaller concentration) would be applied to avoid a tolerance effect. The algometry was performed with a superficial device and a disposable needle of 0.7315 mm. The somatosensory testing was performed at the three trigeminal branches (ophthalmic: front 22 cm above the pupil; maxillary: cheek 21 cm lateral to the nose wing; mandibular: chin skin 21 cm below the lip angle).15,18 The evaluation was performed in a silent room with acoustic protection and the doors closed. The subjects were sitting with their heads resting on a flat surface in the position with the Frankfurt line parallel to the floor. Only the patient and the researcher were in the room. All
http://neuro.psychiatryonline.org
377
SOMATOSENSORY FACIAL ASPECTS
TABLE 2.
Distribution of Age, Sex, Side, and Branch Affected According to the Diagnosis (N=282) Sex (%)
Side affected (%)
ITN (N=162)
60.51611.91 (34–85)
Age (years)
88 (54.3) women
101 (62.3) right 60 (37) left 01 (0.6) bilateral
TMD (N=5)
47.5066.84 (41–56)
5 (100) women
BMS (N=11) PIFP (N=30)
54.2568.63 (35–61) 43.80617.46 (23–76)
11 (100) women 29 (96.7) women
Fibromyalgia (N=5) PHN (N=18)
43.50612.02 (35–52) 71.3368.16 (55–82)
4 (80) women 12 (66.7) women
3 (60) right 2 (40) left 11 (100) bilateral 14 (46.7) right 10 (33.3) left 6 (20) bilateral 5 (100) bilateral 14 (77.8) right 4 (22.2) left
PTN (N=19)
47.94614.74 (32–83)
14 (73.7) women
CH (N=2) DN (N=30) p valuea
40.0060.00 (40) 57.6769.26 (37–77) 0.020
1 (50) woman 12 (40) women ,0.001
5 (26.3) right 13 (68.4) left 1 (5.3) bilateral 2 (100) right 30 (100) bilateral ,0.001
Branch affected (%) 6 50 44 14 40 7 1
(3.7) V1 (30.9) V2 (27.2) V3 (8.6) V1–2 (24.7) V2–3 (4.3) V1–2–3 (0.6) V1–3 — — —
12 2 1 2 1
— (66.7) V1 (11.1) V2 (5.6) V1–2 (11.1) V2–3 (5.6) V1–2–3 — — — ,0.001
BMS: burning mouth syndrome; CH: cervicogenic headache; DN: diabetic neuropathy; ITN: idiopathic trigeminal neuralgia; PHN: trigeminal postherpetic neuralgia; PIFP: persistent idiopathic facial pain; PTN: posttraumatic neuralgia; TMD: temporomandibular disorder; V1: ophthalmic branch; V2: maxillary branch; V3: mandibular branch; V1–2: ophthalmic and maxillary branches; V2–3: maxillary and mandibular branches; V1–2– 3: ophthalmic, maxillary, and mandibular branches; V1–3: ophthalmic and mandibular braches. a One-way analysis of variance, chi-square and Fisher’s exact tests.
patients were evaluated by the same researcher. The patients and control subjects received the same instructions after they were positioned, which were to keep the eyes closed during the exam and that stimulus would be applied at their face and mouth and they should identify TABLE 3.
Numbness and Dysesthesia According to the Diagnosis (N=336)
ITN (N=162) TMD (N=5) BMS (N=11) PIFP (N=30) Fibromyalgia (N=5) PHN (N=18) PTN (N=19) CH (N=2) DN (N=30) Controls (N=54) p valuea
Numbness [N (%)]
Dysesthesia [N (%)]
106 (65.4) 3 (60) 5 (45.5) 15 (50) 3 (60) 16 (88.9) 17 (89.5) 2 (100) 7 (23.3) 5 (9.3) ,0.001
29 (17.9) 3 (60) 5 (45.5) 12 (40) 3 (60) 15 (83.3) 16 (84.2) 0 (0) 4 (13.3) 5 (9.3) ,0.001
BMS: burning mouth syndrome; CH: cervicogenic headache; DN: diabetic neuropathy; ITN: idiopathic trigeminal neuralgia; PHN: trigeminal postherpetic neuralgia; PIFP: persistent idiopathic facial pain; PTN: posttraumatic neuralgia; TMD: temporomandibular disorder. a Chi-square and Fisher’s exact tests.
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and report if they felt it and what they felt (by saying “yes” or “no” and “which was the stimulus”). Only the researcher knew the order of the stimuli. Finally, all findings were tabled and statistically analyzed. 1. Thermal perception. Thermal (cold and warm) tests were performed with the equipment Thermosensi II (Functional Neurosurgery Division, Psychiatry Institute, Hospital das Clinicas, Medical School of the University of São Paulo, Sao Paulo, Brazil). The baseline temperature was 32°C, and the contact area of the thermode was 10310 mm. The stimuli were applied with an amplitude of 0–45°C; the equipment has a temperature change speed of 1°C/sec. 2. Mechanical tactile detection. Tactile tests were performed with standardized von Frey filaments with rounded tips of 0.5 mm of diameter (IITC, Woodland Hills, Calif.) (unit: g/mm2). 3. Pain detection (superficial algometry). Pain thresholds were evaluated at the skin surface with needles of 3030.7 mm perpendicularly applied with a mechanical algometer (Micromar, Diadema, Brazil). (unit: g/mm 2).
J Neuropsychiatry Clin Neurosci 26:4, Fall 2014
DE SIQUEIRA et al.
FIGURE 1.
Impairment of Thermal Detections
A. Cold (p
