- Email: [email protected]
Clinical Investigation of Patients Who Develop Neuropathic Tooth Pain After Endodontic Procedures
Clinical Research
Clinical Investigation of Patients Who Develop Neuropathic Tooth Pain After Endodontic Procedures Katsuo Oshima, DDS, PhD,* Takashi Ishii, DDS, PhD,* Yoko Ogura, DDS, PhD,† Yukio Aoyama, MD, PhD,‡ and Ichiroh Katsuumi, DDS, PhD† Abstract Introduction: This study aimed to determine the characteristics of patients with neuropathic tooth pain (NTP) who were selected from a group of patients who developed persistent pain after undergoing endodontic procedures. Methods: Of 271 patients who had chronic persistent pain that did not respond to previous endodontic procedures and were referred to the Endodontic Team of the Nippon Dental University Hospital, 16 patients (5.9%; mean age, 46.8 years; 13 women) who fulfilled the diagnostic criteria for NTP were recruited. The inclusion criteria for the patients were the presence of chronic persistent pain and other pain-related symptoms, despite the absence of major pathology. Results: Pain predominantly occurred in the maxilla (14 patients). In 10 patients (62.5%), NTP developed after retreatment. Daily application of tricyclic antidepressants produced pain relief in 11 patients (68.8%). Conclusions: These results indicated that NTP is a rare type of chronic intractable endodontic pain and that careful diagnosis of NTP is important. (J Endod 2009;35:958–961)
Key Words
P
rolonged postoperative pain occasionally occurs after endodontic procedures and is most frequently caused by infections or root fractures (1). In general, an appropriate diagnosis and relevant procedures for the treatment of persistent tooth pain are successful in effecting a cure. However, in rare cases, chronic persistent tooth pain does not respond to dental treatment. Some of these cases might be due to neuropathic pain disorders induced by nerve injuries sustained during endodontic procedures. Neuropathic pain is defined as a pain initiated or caused by a primary lesion in or dysfunction of the nervous system (2). Clinically, neuropathic pain is characterized by partial or complete somatosensory change in the innervation territory of a specific part of the peripheral or central nervous system along with the paradoxical presence of pain and hypersensitivity phenomena (3, 4). Several studies have reported that endodontic procedures are related to the development of neuropathic tooth pain (NTP) (5–12). NTP is also known as atypical odontalgia (7) and phantom tooth pain (PTP) (6, 10). Some cases of chronic tooth pain related to endodontic procedures have been reported in which repeated dental treatments failed to provide pain relief (6–8). One study reported that the incidence of NTP after endodontic procedures was greater than that after any other dental treatment such as tooth extraction and trauma (9). Furthermore, 3 retrospective studies have reported that 3%–12% of patients developed NTP after endodontic procedures (10–12). However, very few studies have attempted to investigate patients with NTP who have developed persistent pain after undergoing endodontic procedures. This study aimed to determine the characteristics of suspected patients with NTP disorders who developed these disorders after undergoing endodontic procedures in the endodontic center of our dental hospital.
Chronic tooth pain, endodontic procedures, neuropathic pain, persistent pain, root canal treatment
Materials and Methods
From the *Endodontic Team, Nippon Dental University Hospital; †Department of Endodontics & Operative Dentistry, Nippon Dental University, School of Life Dentistry at Tokyo; and ‡Department of Anesthesiology, Toho University Ohashi Medical Center, Tokyo, Japan. Address requests for reprints to Dr Katsuo Oshima, Endodontic Team, Nippon Dental University Hospital, 2-3-16, Fujimi, Chiyoda-ku, Tokyo 102-8158, Japan. E-mail address: [email protected]. 0099-2399/$0 - see front matter Copyright ª 2009 American Association of Endodontists. doi:10.1016/j.joen.2009.04.017
Subjects This is a retrospective study of patients who had chronic persistent tooth pain that did not respond to endodontic procedures (eg, pulp extirpation, retreatment, and endodontic surgery) and were hence referred to the Endodontic Team of the Nippon Dental University Hospital, Tokyo, Japan, between April 2003 and March 2008. The patients were referred from general dental clinics, secondary referral centers, and other units affiliated with the Nippon Dental University Hospital. Of the 271 patients, 16 (5.9%) met the selection criteria for the study. None of the subjects had tooth pain originating from odontogenic causes such as periapical periodontitis and cracked tooth or from non-neuropathic non-odontogenic causes. Informed consent was obtained according to the guidelines for human research established by the institutional review board of our hospital. Patient Selection The protocol for the selection of patients was as follows. In all patients it was necessary to identify the source of pain. First, we examined the tooth including the root canal and periodontium, because all patients were referred to our team while they were undergoing endodontic procedures. We examined all patients and noted their chief complaints and signs and symptoms, including periapical sensitivity to palpation and percussion, presence of fistula, presence and depth of periodontal pocket, and presence of swelling at the initial visit. The root canals of the patients were examined for the presence of abnormal findings such as tooth fracture and infection; examinations
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Clinical Research were carried out by using a microscope (OPMI PROmagis; Zeiss, Oberkochen, Germany). Radiographic examination was performed for all patients. After these examinations, patients who were diagnosed with tooth pain as a result of odontogenic causes such as periapical periodontitis and cracked tooth were excluded from the study; these patients underwent conventional dental treatment. In cases in which the condition could not be diagnosed, the root canal was filled with calcium hydroxide and sealed with glass ionomer cement, and the patients were reevaluated after about 1 or 2 months. If needed, computed tomography examination was performed for patients in whom a structural lesion such as apical fenestration was suspected (13). In addition, these patients were examined by 3 endodontic specialists, who then discussed the examination findings. The final diagnosis was unanimously reached after joint discussion. Second, we examined the patients with non-odontogenic tooth pain in whom odontogenic causes of tooth pain had been ruled out. The diagnosis of non-odontogenic pain was made in accordance with the guidelines of the American Academy of Orofacial Pain (14) and a few other references (15, 16) and on the basis of the history provided by the patients. Patients with non-odontogenic causes of tooth pain (except NTP), such as trigeminal neuralgia, maxillary sinusitis, cluster headache, and myofascial pain syndrome, were excluded from the study. The patients were examined by a physician specializing in pain management if necessary. When no physical signs were found, we consulted with a psychiatrist to examine somatoform pain disorders. We identified patients with NTP from the non-odontogenic tooth pain group. To diagnose NTP, we conducted clinical interviews to confirm whether the pain ‘‘rarely disrupted sleep’’ and was ‘‘nonresponsive to analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs)’’. Furthermore, we confirmed whether hyperesthesia of the surrounding tissue was present and performed diagnostic local anesthesia at the site of pain. We selected the patients who satisfied all the criteria listed in Table 1 (8, 14–16). For patients who were diagnosed with NTP, we carefully performed root canal filling to avoid excessive stimulation.
Treatment After the patients were diagnosed with NTP, they received appropriate pharmacotherapy with systemic medications. The systemic medications prescribed were medications that are commonly used to treat neuropathic pain: tricyclic antidepressants such as imipramine and amitriptyline and antiepileptics such as gabapentin (16, 17). Initially, all patients were treated with tricyclic antidepressants. The dose was gradually increased until either significant improvement or side effects occurred. When a patient experienced an adverse side effect, we administered an antiepileptic in place of the tricyclic antidepressant. The drug dosage was maintained for a certain period until sufficient analgesia was achieved. The treatment modality and drug dosage were determined on the basis of the severity and type of the patient’s symptoms and hence were not similar for all patients. All patients were treated by the same attending pain clinician (Y.A.). Clinical Evaluation The clinical evaluation consisted of a standardized interview, which included questions about the patient’s medical history; examination of clinical records; and a systematic evaluation of the teeth and other oral structures. The parameters studied were (a) gender and age, (b) pain location, (c) pain duration, (d) pain intensity, (e) precipitating event, and other clinical signs or symptoms at the initial examination. Pain intensity levels were routinely recorded by using a numeric rating scale (NRS) at every visit. On the NRS, pain intensity was graded from levels 0–10, with 0 indicating the complete absence of pain and JOE — Volume 35, Number 7, July 2009
TABLE 1. Diagnostic Criteria for NTP after Endodontic Procedures Pain might be constant dull, burning, or deep ache. Response to hot, cold, or percussion does not reliably relate to the pain and might be disproportionate. No clinical or radiographic signs of pathology (infection, fracture) are present in the tooth. Pain is persistent and remains unchanged for weeks or months. Pain develops within 1 month after endodontic procedures or other dental treatment. Pain rarely disrupts sleep. Response to local anesthesia is ambiguous. Nonresponsive to analgesics, surgery, and dental procedures. Hyperesthesia to palpation at the site of pain. NTP, neuropathic tooth pain. Adapted from references 8, 14–16.
10 indicating the worst pain imaginable. For each patient, the level of pain before treatment and at follow-up visits was recorded in a chart. Pharmacotherapy was considered effective if the patient reported at least 30% pain relief, as recorded on the NRS (18). The statistical significance of the effects of the treatments was calculated by using the Student t test. A probability of less than .05 was considered significant. Data were expressed as means standard error of the mean.
Results Of the 271 patients who consulted the Endodontic Team of the Nippon Dental University Hospital from April 2003–March 2008, a total of 16 patients (5.9%) met the criteria for NTP disorders (Table 1). As shown in Table 2, the majority of patients (13 patients, 81.3%) were female. The average age of the patients was 46.8 9.3 years, with a range of 32–68 years. A total of 14 patients (87.5%) had maxillary pain, and 2 (12.5%) had mandibular pain (Table 2). No significant difference was detected between the incidences of left-sided and right-sided pain (Table 2, Fig. 1). Most patients had pain of moderate intensity (mean score on the NRS, 6.6 1.5) and long duration (mean, 9.8 5.5 months). No statistically significant differences were noted in the pain intensity and pain duration among the patients. Of the 16 patients, 10 (62.5%) reported that the onset of pain coincided with retreatment, and 5 (31.3%) reported that it coincided with pulp extirpation (Table 2). One patient did not report anything specific about the onset of pain. The NRS scores before and after treatment are shown in Fig. 2. After treatment, the pain intensity levels were significantly reduced (6.6 0.4 TABLE 2. Clinical Characteristics of Patients with NTP NTP Patients No. of patients Gender Female Male Age (y) Mean Range Pain location Upper jaw Lower jaw Pain duration (mo) Pain intensity (NRS) Precipitating event Pulp extirpation Retreatment Surgery Unknown
16 13 (81.3%) 3 (18.7%) 46.8 9.3 32–68 14 (87.5%) 2 (12.5%) 9.8 5.5 6.6 1.5 5 (31.3%) 10 (62.5%) 0 1 (6.2%)
NRS, numeric rating scale; NTP, neuropathic tooth pain.
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Figure 1. Distribution of pain locations (indicated by closed circles). Patient number and % number are shown.
versus 3.4 0.5, n = 16 patients, P < .05); in 12 patients (75.0%), the pain intensity drastically decreased. In 11 patients (68.8%), the pain was relieved with daily application of tricyclic antidepressants. The mean daily dose of tricyclic antidepressant was 35.8 21.3 mg, and the mean treatment duration was 10.1 4.7 months. In 1 patient, treatment with antiepileptics was required for pain relief because of adverse side effects to antidepressants. The other 4 patients (25.0%) reported no change in the intensity of pain and dropped out of our treatment.
Discussion In this study we examined the incidence of NTP and the characteristics of patients who had developed NTP after undergoing endodontic procedures and consulted the Endodontic Team of the Nippon Dental University Hospital, Tokyo, Japan, for pain relief. The International Association for the Study of Pain defines neuropathic pain as pain caused by a primary lesion in or dysfunction of the nervous system (2). Clinically, NTP is manifested as a constant dull, burning, or deep ache that develops after dental procedures, despite the absence of any major pathologic findings (3–5). Although the condition has previously been termed atypical odontalgia (7, 16) and PTP (6, 10, 19), recently it was proposed that this condition be considered a neuropathic pain condition (5, 8, 11, 16). Endodontic procedures are known to be related to the development of NTP (5–12, 19). Lynch and Elgeneidy (9) reported that the incidence of NTP after endodontic procedures was higher than that after other dental treatments. In a study by Marbach et al (10), a single endodontist mailed questionnaires to patients 1 month after they had undergone nonsurgical endodontic procedures. Of the 256 patients, 8 (3%) were diagnosed with PTP. Campbell et al (11) reported that 6 of 118 patients (5%) experienced persistent pain after endodontic surgery; the authors considered that this pain was neuropathic in origin. Furthermore, Polycarpou et al (12) carried out a 12- to 59-month follow-up study on 175 patients who underwent endodontic procedures. The authors reported that at the time of review, 21 patients (12%) presented with persistent pain, despite the success of the endodontic procedures. In the present study, NTP was diagnosed in 5.9% of the patients with persistent tooth pain who consulted our team. Although this percentage is similar to that reported in previous studies (10–12), the patient selection protocol in this study differed from that used in previous studies; we recruited the study subjects from a group of patients with chronic persistent pain that did not respond to endodontic treatments. Therefore, the incidence of NTP in this study cannot be directly compared with that reported in previous studies. However, it is clear that endodontic procedures can cause NTP, albeit rarely (9–12). With regard to the pathognomonic features of NTP, several studies have reported that NTP tends to occur among women in their mid-40s 960
Oshima et al.
Figure 2. Pain intensity before and after treatment. Each column represents the mean standard error of the mean (pain intensity before treatment versus that after treatment). Empty column, NRS score at initial visit (n = 16); black column, NRS score after treatment (n = 16). *Statistically significant difference (P < .05) from pretreatment values.
and that it most commonly involves the maxillary molars and premolars (5, 8, 12, 16). In our study, the majority of the patients were female (81.3%), their mean age was 46.8 years, and in most of them, the pain was localized in the maxilla (87.5%). These characteristics resemble those reported in other studies. The pathophysiology of NTP, however, remains indistinct, which indicates the complexity of the disease. Several studies have reported that neuropathic pain is characterized by partial or complete somatosensory change in the innervation territory of a specific part of the peripheral or central nervous system along with the paradoxical presence of pain and hypersensitivity phenomena (4, 5). In addition, it is well-known that NTP is hardly alleviated by conventional dental treatments alone (5–12, 16, 17). In this study, 68.8% (11/16) of patients reported that their symptoms improved after the administration of antidepressants. Several studies have reported the effectiveness of antidepressants against NTP (16, 17). It is likely that this effect is not related to the management of depression but rather to the analgesic effect of relatively low dosages of antidepressants (17). These medications inhibit the reuptake of serotonin and norepinephrine, thus increasing the effectiveness of the descending inhibitory system (20). Complete elimination of the pain, however, remains difficult, and satisfactory treatment methods for NTP are yet to established (17). Little is known about the mechanism underlying the development of chronic persistent pain after endodontic procedures. It has been reported that persistent pain tends to develop in patients in whom endodontic procedures were performed under insufficient anesthesia and in patients who experienced pain before undergoing the procedures (21, 22). An animal study has reported that brainstem neurons are altered after tooth pulp removal (23). However, Vickers and Cousins (5) suggested that it is impossible at this stage to categorically state that endodontic procedures are prime causal factors in the development of NTP. They consider that although various endodontic procedures inflict mechanical and chemical trauma on pulpal and periodontal nociceptors, preexisting pulpitis might well be the trigger for NTP. In addition, it is thought that the peripheral sensitization after repeated dental procedures might also induce sensitization of the central trigeminal nociceptive neurons; central sensitization appears to be a key factor in the development of many chronic orofacial pain conditions (3, 5, 23, 24). Central sensitization can be initiated and/ or maintained by ectopic impulses that might be induced by dental
JOE — Volume 35, Number 7, July 2009
Clinical Research procedures. Consequently, central neuroplastic changes are progressively reversed during a period of several days or weeks. Taken together, these observations show that it is possible that NTP is caused by chronic inflammation such as chronic pulpitis and chronic apical periodontitis and/or mechanical and chemical stimulation caused by repeated endodontic procedures rather than by nerve amputation. This hypothesis is supported by the fact that in our study, 10 patients (62.5%) reported the development of pain after retreatment. However, several studies have reported that the onset and duration of chronic pain are closely related to psychogenic phenomena (16, 25, 26). Moreover, as mentioned above, various factors such as sex, age, and site of involvement influence the onset of NTP (27). Therefore, the mechanisms underlying the development of NTP after endodontic procedures seem complex, and further studies are required to elucidate these. In summary, this study has reviewed a small group (5.9%, 16/271) of patients who developed NTP after undergoing endodontic procedures. A distinct female predilection was seen (13:3). Majority of the patients (87.5%, 14/16) had maxillary pain, and most patients (62.5%, 10/16) developed pain after undergoing retreatment. Tricyclic antidepressants produced pain relief in 11 (68.8%) patients.
References 1. Kenneth M, Hargreaves KM, Byrne B. Analgesics in endodontics. In: Cohen S, Hargreaves KM, eds. Pathways of the pulp. 9th ed. St Louis, MO: CV Mosby; 2006:668–90. 2. Merskey H, Bogduk N. Classification of chronic pain. 2nd ed. Seattle, WA: IASP Press; 1994. 3. Woolf CJ, Mannion RJ. Neuropathic pain: aetiology, symptoms, mechanisms and management. Lancet 1999;353:1959–64. 4. Finnerup NB, Otto M, McQuay HJ, Jensen TS, Sindrup SH. Algorithm for neuropathic pain treatment: an evidence based proposal. Pain 2005;118:289–305. 5. Vickers ER, Cousins MJ. Neuropathic orofacial pain: part 1—prevalence and pathophysiology. Aust Endod J 2000;26:19–26. 6. Battrum DE, Gutmann JL. Phantom tooth pain: a diagnosis of exclusion. Int Endod J 1996;29:190–4. 7. Lilly JP, Law AS. Atypical odontalgia misdiagnosed as odontogenic pain: a case report and discussion of treatment. J Endod 1997;23:337–9.
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8. Matwychuk MJ. Diagnostic challenges of neuropathic tooth pain. J Can Dent Assoc 2004;70:542–6. 9. Lynch ME, Elgeneidy AK. The role of sympathetic activity in neuropathic orofacial pain. J Orofac Pain 1996;10:297–305. 10. Marbach JJ, Hulbrock J, Hohn C, Segal AG. Incidence of phantom tooth pain: an atypical facial neuralgia. Oral Surg Oral Med Oral Pathol 1982;53:190–3. 11. Campbell RL, Parks KW, Dodds RN. Chronic facial pain associated with endodontic therapy. Oral Surg Oral Med Oral Pathol 1990;69:287–90. 12. Polycarpou N, Ng YL, Canavan D, Moles DR, Gulabivala K. Prevalence of persistent pain after endodontic treatment and factors affecting its occurrence in cases with complete radiographic healing. Int Endod J 2005;38:169–78. 13. Boucher Y, Sobel M, Sauveur G. Persistent pain related to root canal filling and apical fenestration: a case report. J Endod 2000;26:242–4. 14. Okeson JP. Orofacial pain: guidelines for assessment, diagnosis and management. Chicago: Quintessence; 1996. 15. Okeson JP. Non-odontogenic toothache. Northwest Dent 2000;79:37–44. 16. Melis M, Lobo SL, Ceneviz C, et al. Atypical odontalgia: a review of the literature. Headache 2003;43:1060–74. 17. Lewis MA, Sankar V, De Laat A, Benoliel R. Management of neuropathic orofacial pain. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103:32–8. 18. Farrar JT, Young JP Jr., LaMoreaux L, Werth JL, Poole RM. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain 2001;94:149–58. 19. Marbach JJ. Phantom tooth pain. J Endod 1978;4:362–72. 20. Lynch ME. Antidepressants as analgesics: a review of randomized controlled trials. J Psychiatry Neurosci 2001;26:30–6. 21. Hutchison GL, Crofts SL, Gray IG. Preoperative piroxicam for postoperative analgesia in dental surgery. Br J Anaesth 1990;65:500–3. 22. Bach S, Noreng MF, Tje´llden NU. Phantom limb pain in amputees during the first 12 months following limb amputation, after preoperative lumbar epidural blockade. Pain 1988;33:297–301. 23. Sessle BJ. Acute and chronic craniofacial pain: brainstem mechanisms of nociceptive transmission and neuroplasticity, and their clinical correlates. Crit Rev Oral Biol Med 2000;11:57–91. 24. Dubner R, Ren K. Brainstem mechanisms of persistent pain following injury. J Orofac Pain 2004;18:299–305. 25. Ikawa M, Yamada K, Ikeuchi S. Efficacy of amitriptyline for treatment of somatoform pain disorder in the orofacial region: a case series. J Orofac Pain 2006;20: 234–40. 26. List T, Leijon G, Helkimo M, Oster A, Dworkin SF, Svensson P. Clinical findings and psychosocial factors in patients with atypical odontalgia: a case-control study. J Orofac Pain 2007;21:89–98. 27. Berkley KJ. Sex differences in pain. Behav Brain Sci 1997;20:371–80.
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Clinical Investigation of Patients Who Develop Neuropathic Tooth Pain After Endodontic Procedures Katsuo Oshima, DDS, PhD,* Takashi Ishii, DDS, PhD,* Yoko Ogura, DDS, PhD,† Yukio Aoyama, MD, PhD,‡ and Ichiroh Katsuumi, DDS, PhD† Abstract Introduction: This study aimed to determine the characteristics of patients with neuropathic tooth pain (NTP) who were selected from a group of patients who developed persistent pain after undergoing endodontic procedures. Methods: Of 271 patients who had chronic persistent pain that did not respond to previous endodontic procedures and were referred to the Endodontic Team of the Nippon Dental University Hospital, 16 patients (5.9%; mean age, 46.8 years; 13 women) who fulfilled the diagnostic criteria for NTP were recruited. The inclusion criteria for the patients were the presence of chronic persistent pain and other pain-related symptoms, despite the absence of major pathology. Results: Pain predominantly occurred in the maxilla (14 patients). In 10 patients (62.5%), NTP developed after retreatment. Daily application of tricyclic antidepressants produced pain relief in 11 patients (68.8%). Conclusions: These results indicated that NTP is a rare type of chronic intractable endodontic pain and that careful diagnosis of NTP is important. (J Endod 2009;35:958–961)
Key Words
P
rolonged postoperative pain occasionally occurs after endodontic procedures and is most frequently caused by infections or root fractures (1). In general, an appropriate diagnosis and relevant procedures for the treatment of persistent tooth pain are successful in effecting a cure. However, in rare cases, chronic persistent tooth pain does not respond to dental treatment. Some of these cases might be due to neuropathic pain disorders induced by nerve injuries sustained during endodontic procedures. Neuropathic pain is defined as a pain initiated or caused by a primary lesion in or dysfunction of the nervous system (2). Clinically, neuropathic pain is characterized by partial or complete somatosensory change in the innervation territory of a specific part of the peripheral or central nervous system along with the paradoxical presence of pain and hypersensitivity phenomena (3, 4). Several studies have reported that endodontic procedures are related to the development of neuropathic tooth pain (NTP) (5–12). NTP is also known as atypical odontalgia (7) and phantom tooth pain (PTP) (6, 10). Some cases of chronic tooth pain related to endodontic procedures have been reported in which repeated dental treatments failed to provide pain relief (6–8). One study reported that the incidence of NTP after endodontic procedures was greater than that after any other dental treatment such as tooth extraction and trauma (9). Furthermore, 3 retrospective studies have reported that 3%–12% of patients developed NTP after endodontic procedures (10–12). However, very few studies have attempted to investigate patients with NTP who have developed persistent pain after undergoing endodontic procedures. This study aimed to determine the characteristics of suspected patients with NTP disorders who developed these disorders after undergoing endodontic procedures in the endodontic center of our dental hospital.
Chronic tooth pain, endodontic procedures, neuropathic pain, persistent pain, root canal treatment
Materials and Methods
From the *Endodontic Team, Nippon Dental University Hospital; †Department of Endodontics & Operative Dentistry, Nippon Dental University, School of Life Dentistry at Tokyo; and ‡Department of Anesthesiology, Toho University Ohashi Medical Center, Tokyo, Japan. Address requests for reprints to Dr Katsuo Oshima, Endodontic Team, Nippon Dental University Hospital, 2-3-16, Fujimi, Chiyoda-ku, Tokyo 102-8158, Japan. E-mail address: [email protected]. 0099-2399/$0 - see front matter Copyright ª 2009 American Association of Endodontists. doi:10.1016/j.joen.2009.04.017
Subjects This is a retrospective study of patients who had chronic persistent tooth pain that did not respond to endodontic procedures (eg, pulp extirpation, retreatment, and endodontic surgery) and were hence referred to the Endodontic Team of the Nippon Dental University Hospital, Tokyo, Japan, between April 2003 and March 2008. The patients were referred from general dental clinics, secondary referral centers, and other units affiliated with the Nippon Dental University Hospital. Of the 271 patients, 16 (5.9%) met the selection criteria for the study. None of the subjects had tooth pain originating from odontogenic causes such as periapical periodontitis and cracked tooth or from non-neuropathic non-odontogenic causes. Informed consent was obtained according to the guidelines for human research established by the institutional review board of our hospital. Patient Selection The protocol for the selection of patients was as follows. In all patients it was necessary to identify the source of pain. First, we examined the tooth including the root canal and periodontium, because all patients were referred to our team while they were undergoing endodontic procedures. We examined all patients and noted their chief complaints and signs and symptoms, including periapical sensitivity to palpation and percussion, presence of fistula, presence and depth of periodontal pocket, and presence of swelling at the initial visit. The root canals of the patients were examined for the presence of abnormal findings such as tooth fracture and infection; examinations
958
Oshima et al.
JOE — Volume 35, Number 7, July 2009
Clinical Research were carried out by using a microscope (OPMI PROmagis; Zeiss, Oberkochen, Germany). Radiographic examination was performed for all patients. After these examinations, patients who were diagnosed with tooth pain as a result of odontogenic causes such as periapical periodontitis and cracked tooth were excluded from the study; these patients underwent conventional dental treatment. In cases in which the condition could not be diagnosed, the root canal was filled with calcium hydroxide and sealed with glass ionomer cement, and the patients were reevaluated after about 1 or 2 months. If needed, computed tomography examination was performed for patients in whom a structural lesion such as apical fenestration was suspected (13). In addition, these patients were examined by 3 endodontic specialists, who then discussed the examination findings. The final diagnosis was unanimously reached after joint discussion. Second, we examined the patients with non-odontogenic tooth pain in whom odontogenic causes of tooth pain had been ruled out. The diagnosis of non-odontogenic pain was made in accordance with the guidelines of the American Academy of Orofacial Pain (14) and a few other references (15, 16) and on the basis of the history provided by the patients. Patients with non-odontogenic causes of tooth pain (except NTP), such as trigeminal neuralgia, maxillary sinusitis, cluster headache, and myofascial pain syndrome, were excluded from the study. The patients were examined by a physician specializing in pain management if necessary. When no physical signs were found, we consulted with a psychiatrist to examine somatoform pain disorders. We identified patients with NTP from the non-odontogenic tooth pain group. To diagnose NTP, we conducted clinical interviews to confirm whether the pain ‘‘rarely disrupted sleep’’ and was ‘‘nonresponsive to analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs)’’. Furthermore, we confirmed whether hyperesthesia of the surrounding tissue was present and performed diagnostic local anesthesia at the site of pain. We selected the patients who satisfied all the criteria listed in Table 1 (8, 14–16). For patients who were diagnosed with NTP, we carefully performed root canal filling to avoid excessive stimulation.
Treatment After the patients were diagnosed with NTP, they received appropriate pharmacotherapy with systemic medications. The systemic medications prescribed were medications that are commonly used to treat neuropathic pain: tricyclic antidepressants such as imipramine and amitriptyline and antiepileptics such as gabapentin (16, 17). Initially, all patients were treated with tricyclic antidepressants. The dose was gradually increased until either significant improvement or side effects occurred. When a patient experienced an adverse side effect, we administered an antiepileptic in place of the tricyclic antidepressant. The drug dosage was maintained for a certain period until sufficient analgesia was achieved. The treatment modality and drug dosage were determined on the basis of the severity and type of the patient’s symptoms and hence were not similar for all patients. All patients were treated by the same attending pain clinician (Y.A.). Clinical Evaluation The clinical evaluation consisted of a standardized interview, which included questions about the patient’s medical history; examination of clinical records; and a systematic evaluation of the teeth and other oral structures. The parameters studied were (a) gender and age, (b) pain location, (c) pain duration, (d) pain intensity, (e) precipitating event, and other clinical signs or symptoms at the initial examination. Pain intensity levels were routinely recorded by using a numeric rating scale (NRS) at every visit. On the NRS, pain intensity was graded from levels 0–10, with 0 indicating the complete absence of pain and JOE — Volume 35, Number 7, July 2009
TABLE 1. Diagnostic Criteria for NTP after Endodontic Procedures Pain might be constant dull, burning, or deep ache. Response to hot, cold, or percussion does not reliably relate to the pain and might be disproportionate. No clinical or radiographic signs of pathology (infection, fracture) are present in the tooth. Pain is persistent and remains unchanged for weeks or months. Pain develops within 1 month after endodontic procedures or other dental treatment. Pain rarely disrupts sleep. Response to local anesthesia is ambiguous. Nonresponsive to analgesics, surgery, and dental procedures. Hyperesthesia to palpation at the site of pain. NTP, neuropathic tooth pain. Adapted from references 8, 14–16.
10 indicating the worst pain imaginable. For each patient, the level of pain before treatment and at follow-up visits was recorded in a chart. Pharmacotherapy was considered effective if the patient reported at least 30% pain relief, as recorded on the NRS (18). The statistical significance of the effects of the treatments was calculated by using the Student t test. A probability of less than .05 was considered significant. Data were expressed as means standard error of the mean.
Results Of the 271 patients who consulted the Endodontic Team of the Nippon Dental University Hospital from April 2003–March 2008, a total of 16 patients (5.9%) met the criteria for NTP disorders (Table 1). As shown in Table 2, the majority of patients (13 patients, 81.3%) were female. The average age of the patients was 46.8 9.3 years, with a range of 32–68 years. A total of 14 patients (87.5%) had maxillary pain, and 2 (12.5%) had mandibular pain (Table 2). No significant difference was detected between the incidences of left-sided and right-sided pain (Table 2, Fig. 1). Most patients had pain of moderate intensity (mean score on the NRS, 6.6 1.5) and long duration (mean, 9.8 5.5 months). No statistically significant differences were noted in the pain intensity and pain duration among the patients. Of the 16 patients, 10 (62.5%) reported that the onset of pain coincided with retreatment, and 5 (31.3%) reported that it coincided with pulp extirpation (Table 2). One patient did not report anything specific about the onset of pain. The NRS scores before and after treatment are shown in Fig. 2. After treatment, the pain intensity levels were significantly reduced (6.6 0.4 TABLE 2. Clinical Characteristics of Patients with NTP NTP Patients No. of patients Gender Female Male Age (y) Mean Range Pain location Upper jaw Lower jaw Pain duration (mo) Pain intensity (NRS) Precipitating event Pulp extirpation Retreatment Surgery Unknown
16 13 (81.3%) 3 (18.7%) 46.8 9.3 32–68 14 (87.5%) 2 (12.5%) 9.8 5.5 6.6 1.5 5 (31.3%) 10 (62.5%) 0 1 (6.2%)
NRS, numeric rating scale; NTP, neuropathic tooth pain.
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Figure 1. Distribution of pain locations (indicated by closed circles). Patient number and % number are shown.
versus 3.4 0.5, n = 16 patients, P < .05); in 12 patients (75.0%), the pain intensity drastically decreased. In 11 patients (68.8%), the pain was relieved with daily application of tricyclic antidepressants. The mean daily dose of tricyclic antidepressant was 35.8 21.3 mg, and the mean treatment duration was 10.1 4.7 months. In 1 patient, treatment with antiepileptics was required for pain relief because of adverse side effects to antidepressants. The other 4 patients (25.0%) reported no change in the intensity of pain and dropped out of our treatment.
Discussion In this study we examined the incidence of NTP and the characteristics of patients who had developed NTP after undergoing endodontic procedures and consulted the Endodontic Team of the Nippon Dental University Hospital, Tokyo, Japan, for pain relief. The International Association for the Study of Pain defines neuropathic pain as pain caused by a primary lesion in or dysfunction of the nervous system (2). Clinically, NTP is manifested as a constant dull, burning, or deep ache that develops after dental procedures, despite the absence of any major pathologic findings (3–5). Although the condition has previously been termed atypical odontalgia (7, 16) and PTP (6, 10, 19), recently it was proposed that this condition be considered a neuropathic pain condition (5, 8, 11, 16). Endodontic procedures are known to be related to the development of NTP (5–12, 19). Lynch and Elgeneidy (9) reported that the incidence of NTP after endodontic procedures was higher than that after other dental treatments. In a study by Marbach et al (10), a single endodontist mailed questionnaires to patients 1 month after they had undergone nonsurgical endodontic procedures. Of the 256 patients, 8 (3%) were diagnosed with PTP. Campbell et al (11) reported that 6 of 118 patients (5%) experienced persistent pain after endodontic surgery; the authors considered that this pain was neuropathic in origin. Furthermore, Polycarpou et al (12) carried out a 12- to 59-month follow-up study on 175 patients who underwent endodontic procedures. The authors reported that at the time of review, 21 patients (12%) presented with persistent pain, despite the success of the endodontic procedures. In the present study, NTP was diagnosed in 5.9% of the patients with persistent tooth pain who consulted our team. Although this percentage is similar to that reported in previous studies (10–12), the patient selection protocol in this study differed from that used in previous studies; we recruited the study subjects from a group of patients with chronic persistent pain that did not respond to endodontic treatments. Therefore, the incidence of NTP in this study cannot be directly compared with that reported in previous studies. However, it is clear that endodontic procedures can cause NTP, albeit rarely (9–12). With regard to the pathognomonic features of NTP, several studies have reported that NTP tends to occur among women in their mid-40s 960
Oshima et al.
Figure 2. Pain intensity before and after treatment. Each column represents the mean standard error of the mean (pain intensity before treatment versus that after treatment). Empty column, NRS score at initial visit (n = 16); black column, NRS score after treatment (n = 16). *Statistically significant difference (P < .05) from pretreatment values.
and that it most commonly involves the maxillary molars and premolars (5, 8, 12, 16). In our study, the majority of the patients were female (81.3%), their mean age was 46.8 years, and in most of them, the pain was localized in the maxilla (87.5%). These characteristics resemble those reported in other studies. The pathophysiology of NTP, however, remains indistinct, which indicates the complexity of the disease. Several studies have reported that neuropathic pain is characterized by partial or complete somatosensory change in the innervation territory of a specific part of the peripheral or central nervous system along with the paradoxical presence of pain and hypersensitivity phenomena (4, 5). In addition, it is well-known that NTP is hardly alleviated by conventional dental treatments alone (5–12, 16, 17). In this study, 68.8% (11/16) of patients reported that their symptoms improved after the administration of antidepressants. Several studies have reported the effectiveness of antidepressants against NTP (16, 17). It is likely that this effect is not related to the management of depression but rather to the analgesic effect of relatively low dosages of antidepressants (17). These medications inhibit the reuptake of serotonin and norepinephrine, thus increasing the effectiveness of the descending inhibitory system (20). Complete elimination of the pain, however, remains difficult, and satisfactory treatment methods for NTP are yet to established (17). Little is known about the mechanism underlying the development of chronic persistent pain after endodontic procedures. It has been reported that persistent pain tends to develop in patients in whom endodontic procedures were performed under insufficient anesthesia and in patients who experienced pain before undergoing the procedures (21, 22). An animal study has reported that brainstem neurons are altered after tooth pulp removal (23). However, Vickers and Cousins (5) suggested that it is impossible at this stage to categorically state that endodontic procedures are prime causal factors in the development of NTP. They consider that although various endodontic procedures inflict mechanical and chemical trauma on pulpal and periodontal nociceptors, preexisting pulpitis might well be the trigger for NTP. In addition, it is thought that the peripheral sensitization after repeated dental procedures might also induce sensitization of the central trigeminal nociceptive neurons; central sensitization appears to be a key factor in the development of many chronic orofacial pain conditions (3, 5, 23, 24). Central sensitization can be initiated and/ or maintained by ectopic impulses that might be induced by dental
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Clinical Research procedures. Consequently, central neuroplastic changes are progressively reversed during a period of several days or weeks. Taken together, these observations show that it is possible that NTP is caused by chronic inflammation such as chronic pulpitis and chronic apical periodontitis and/or mechanical and chemical stimulation caused by repeated endodontic procedures rather than by nerve amputation. This hypothesis is supported by the fact that in our study, 10 patients (62.5%) reported the development of pain after retreatment. However, several studies have reported that the onset and duration of chronic pain are closely related to psychogenic phenomena (16, 25, 26). Moreover, as mentioned above, various factors such as sex, age, and site of involvement influence the onset of NTP (27). Therefore, the mechanisms underlying the development of NTP after endodontic procedures seem complex, and further studies are required to elucidate these. In summary, this study has reviewed a small group (5.9%, 16/271) of patients who developed NTP after undergoing endodontic procedures. A distinct female predilection was seen (13:3). Majority of the patients (87.5%, 14/16) had maxillary pain, and most patients (62.5%, 10/16) developed pain after undergoing retreatment. Tricyclic antidepressants produced pain relief in 11 (68.8%) patients.
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