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The Incidence of Mechanical Allodynia in Patients With Irreversible Pulpitis
Clinical Research
The Incidence of Mechanical Allodynia in Patients With Irreversible Pulpitis Christopher B. Owatz, DMD,* Asma A. Khan, BDS, PhD,* William G. Schindler, DDS, MS, Scott A. Schwartz, DDS, Karl Keiser, DDS, MS, and Kenneth M. Hargreaves, DDS, PhD Abstract The mechanisms of odontogenic pain are complex and incompletely understood. Cases of irreversible pulpitis are thought to represent a localized inflammatory response to bacterial challenge in dental pulp tissue. The presenting symptoms are classically defined by exaggerated painful episodes to thermal stimuli that may linger after cessation of the stimulus. However, the associated incidence of mechanical allodynia, defined as reduced mechanical pain threshold to masticatory forces, has not been characterized. This study evaluated pain intensity ratings and the presence of mechanical allodynia reported by 993 consecutive dental patients presenting for tooth extraction in a community health center. After clinical and radiographic examinations, the pulpal/periradicular diagnostic categories were normal pulp/normal periradicular (n ⫽ 792 patients), irreversible pulpitis/normal periradicular (n ⫽ 86), or irreversible pulpitis/acute periradicular periodontitis (n ⫽ 115). The rank order for the mean values of pain intensity ratings was irreversible pulpitis/acute periradicular periodontitis ⬎ irreversible pulpitis/normal periradicular ⬎ normal/normal (p ⬍ 0.05 for all comparisons). The incidence of mechanical allodynia in patients presenting with irreversible pulpitis was 57.2%, indicating that periradicular mechanical allodynia contributes to early stages of odontogenic pain because of inflammation of vital pulpal tissue. (J Endod 2007;33:552–558)
Key Words Acute periradicular periodontitis, incidence, irreversible pulpitis, mechanical allodynia, pain
From the Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, Texas. Supported in part by P01 DA16719 (KMH), R01 NS45186 (KMH), and K23 DE14864 (AAK). Address requests for reprints to Dr. Christopher B. Owatz, University of Texas Health Science Center at San Antonio, Department of Endodontics, MC 7892, 7703 Floyd Curl Dr, San Antonio, TX 78229. E-mail address: [email protected]. 0099-2399/$0 - see front matter Copyright © 2007 by the American Association of Endodontists. doi:10.1016/j.joen.2007.01.023
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Owatz et al.
O
rofacial pain is very common among the general population. A survey of noninstitutionalized civilian residents of the United States showed that 28% of the population reported experiencing orofacial pain in the preceding 6 months, with the most common report being odontalgia (1). Odontogenic pain can be caused by activation of pulpal or periradicular nociceptors. There are two hallmark features of many clinical pain conditions: Allodynia is defined as a reduction in pain threshold, whereby pain occurs in response to innocuous mechanical or thermal stimulation. Conversely, hyperalgesia is defined as an increased or exaggerated responsiveness to normally noxious mechanical or thermal stimuli. Both of these features are evaluated in endodontic clinical testing. Mechanical allodynia is typically evaluated by a percussion test and a response is deemed positive if this innocuous tapping produces a sensation of pain. Thermal hyperalgesia is generally evaluated by application of a cold stimulus that is sufficient to produce a transient and slight sensation of pain in a control tooth but evokes a prolonged or intense sensation of pain when applied to a tooth with irreversible pulpitis. Clinical research (2) indicates that the presentation of thermal hyperalgesia is primarily mediated by pulpal nociceptive mechanisms (odds ratio, 9.0), whereas mechanical allodynia is primarily mediated by periradicular nociceptive mechanisms (odds ratio, 6.9). Irreversible pulpitis generally originates as a localized inflammatory response to bacterial invasion of the pulp-dentin complex. It is speculated that irreversible pulpitis, often characterized by brief, intense painful episodes to thermal stimuli that linger after cessation of the stimulus, is one of the most frequent reasons that patients seek emergency dental care (3). The mechanisms for this pain are thought to be caused by sensitization and activation of pulpal nociceptors because of local release of inflammatory mediators (4). However, this model does not explain why periradicular mechanical allodynia would be present in these patients. To begin to identify mechanisms and resultant signs and symptoms of odontogenic pain, we have characterized thermal and mechanical allodynia in a group of 993 patients presenting for tooth extraction at a local community health center.
Materials and Methods The Institutional Review Board of the University of Texas Health Science Center at San Antonio approved this study, and the informed consent of all human subjects who participated in the investigation was obtained. Patients experiencing odontogenic pain and/or presenting for dental extractions at the University Health Center Downtown Facility, University of Texas Health Science Center at San Antonio were invited to participate. Patients were excluded if they were unable or unwilling to provide informed consent. Information was recorded regarding the patient’s ethnicity, sex, age and tooth number for which they were seeking emergency treatment. Patients used validated pain intensity scales to rate both their current level of spontaneous pain and their recalled level of “worst pain ever.” The spontaneous pain was described to the patient as pain without stimulation on the day of their appointment, and their “worst pain ever” was described to the patient as the most intense pain they had ever experienced associated with the tooth to be treated. The patients rated their spontaneous and worst pain ever pain intensity on a four-point category scale (none, mild, moderate, and severe) and the 100-mm visual analog scale (VAS). One examiner determined the pulpal and periradicular diagnoses of all patients. To determine the pulpal status, a 6-inch cotton tipped applicator was saturated with
JOE — Volume 33, Number 5, May 2007
Clinical Research TABLE 1. Mean age, sex, and ethnic distribution of dental patients Pulpal and Periradicular Diagnosis Normal pulp/ normal periradicular Irreversible pulpitis/ normal periradicular Irreversible pulpitis/ acute periradicular periodontitis All subjects
Sex
Ethnicity
n
Mean Age
Male
Female
Hispanic
Black
White
Asian
Other
792
32.6
34% (268)
66% (524)
60.2% (477)
9.0% (71)
27.9% (221)
2.5% (20)
0.4% (3)
86
42.6
44% (38)
56% (48)
62.8% (54)
30.2% (26)
7.0% (6)
0.0% (0)
0.0% (0)
115
43.6
37% (43)
63% (72)
59.1% (68)
9.6% (11)
28.7% (33)
1.7% (2)
0.9% (1)
993
34.7
35% (349)
65% (644)
60.3% (599)
10.9% (108)
26.2% (260)
2.2% (22)
0.4% (4)
TABLE 2. Distribution by tooth type: percentage (number) Pulpal and Periradicular Diagnosis Normal/normal (792) Irreversible pulpitis/ normal (86) Irreversible pulpitis/ acute periradicular periodontitis (115)
Maxillary Anteriors
Mandibular Anteriors
Maxillary Premolars
Mandibular Premolars
Maxillary First and Second Molars
Mandibular First and Second Molars
Maxillary Third Molars
Mandibular Third Molars
2.8% (22) 8.1% (7)
8.7% (69) 8.1% (7)
1.6% (13) 11.6% (10)
5.3% (42) 4.7% (4)
2.8% (22) 30.2% (26)
2.8% (22) 17.4% (15)
39.1% (310) 8.1% (7)
36.9% (292) 11.6% (10)
8.7% (10)
3.5% (4)
16.5% (19)
8.7% (10)
26.1% (30)
16.5% (19)
13.0% (15)
7.0% (8)
Endo-Ice refrigerant spray (Coltène/Whaledent, Cuyahoga Falls, OH) and applied first to a control tooth (contralateral side) and then to the tooth in question. A diagnosis of a normal pulp occurred when the patient felt a cold sensation that subsided once the stimulus was removed, and a diagnosis of irreversible pulpitis occurred when the patient reported an exaggerated response to the cold sensation that lingered as a dull ache once the stimulus was removed. Patients with a diagnosis of pulpal necrosis were not included in this study. To determine the periradicular status, the examiner first percussed a control tooth (contralateral side) by using the handle of a mouth mirror and then the tooth in question. A diagnosis of a normal periradicular tissue occurred when the percussed tooth was not tender (similar sensation as the control tooth), and a diagnosis of acute periradicular periodontitis occurred when the patient reported tenderness to percussion. All patients included in this study had either normal periradicular radiographic anatomy or no more than a 2-fold widening of the periodontal ligament space. Mean spontaneous pain and “worst pain ever” pain intensity ratings were calculated for each of the following three groups: (1) normal pulp and normal periradicular tissues, (2) irreversible pulpitis and normal periradicular tissues, and (3) irreversible pulpitis and acute periradicular periodontitis. The data are presented as mean value ⫾ standard error of the mean (SEM) and were analyzed by using a oneway analysis of variance (ANOVA) and Tukey post hoc test. A difference was considered significant at p ⬍ 0.05.
and thus by definition were considered to have mechanical allodynia; this criterion was used to subdivide these patients into a group having normal periradicular tissue and a group having acute periradicular periodontitis. As shown in Figure 1, the spontaneous pain intensity reported by the patient on the day of the dental appointment differed significantly among patients diagnosed with normal pulp and normal periradicular tissue (8.1 ⫾ 0.8 mm VAS), irreversible pulpitis with normal periradicular tissue (25.3 ⫾ 3.4 mm VAS), and irreversible pulpitis with acute periradicular periodontitis (44.0 ⫾ 3.2 mm VAS). Analysis of the results from the category pain scale for spontaneous pain data showed a similar trend to the 100-mm VAS data. The weighted mean values were 0.26 for normal pulp and normal periradicular tissue, 0.76 for irreversible pulpitis and normal periradicular tissue, and 1.51 for irreversible pulpitis and acute periradicular periodontitis.
Results There were 993 subjects included in the study. Table 1 summarizes the mean age and the sex and ethnic distribution for each of the three diagnostic groups. The patient distribution by tooth type is displayed in Table 2. There were no significant differences among the three groups for any of the variables except for mean age and percentage of third molars. The normal pulp/normal periradicular group was significantly different from the irreversible pulpitis/normal periradicular and the irreversible pulpitis/acute periradicular periodontitis groups for these variables (p ⬍ 0.001); the latter two groups were not significantly different from each other. Of the 201 patients diagnosed with irreversible pulpitis, 57.2% had concomitant acute periradicular periodontitis
JOE — Volume 33, Number 5, May 2007
Figure 1. Spontaneous pain intensity experienced by the patient on the day of data collection, reported on the 100-mm VAS, presented as mean values ⫾ SEM. Differences between all groups were statistically significant when analyzed with the one-way ANOVA and Tukey post hoc test (**p ⬍ 0.001).
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Clinical Research data. The weighted mean values were 1.45 for normal pulp and normal periradicular tissue, 2.31 for irreversible pulpitis and normal periradicular tissue, and 2.58 for irreversible pulpitis and acute periradicular periodontitis.
Discussion
Figure 2. Worst pain ever pain intensity experienced by the patient, reported on the 100 mm VAS, presented as mean values ⫾ SEM. Differences between all groups were statistically significant when analyzed with the one-way ANOVA and Tukey post hoc test (**p ⬍ 0.001, *p ⬍ 0.05).
Figure 2 presents the “worst pain ever” pain intensity reported by the patient on the day of the dental appointment. These pain values differed significantly among patients diagnosed with normal pulp and normal periradicular tissue (41.1 ⫾ 1.4 mm VAS), irreversible pulpitis with normal periradicular tissue (70.0 ⫾ 3.8 mm VAS), and irreversible pulpitis with acute periradicular periodontitis (85.4 ⫾ 1.6 mm VAS). Analysis of the results from the category pain scale for “worst pain ever” pain intensity data showed a similar trend to the 100-mm VAS
In this study, we examined the incidence of mechanical allodynia among dental patients presenting with odontalgia and/or an indication for tooth extraction. These patients also rated their spontaneous and “worst pain ever” pain intensity to determine if mechanical allodynia occurred more frequently in patients with increased reported pain levels. Our results show that ⬎50% of the patients diagnosed with irreversible pulpitis were also diagnosed with mechanical allodynia. In addition, patients diagnosed with irreversible pulpitis and mechanical allodynia rated their spontaneous and “worst pain ever” pain intensity as significantly greater than those patients with irreversible pulpitis and normal periradicular tissues. Although patients with normal pulpal and periradicular diagnoses would be expected to report no pain, they might have a history of pain from a prior exacerbation of periodontal disease, an episode of pericoronitis, or another inflammatory condition. Seventy-six percent of the subjects in the normal pulp and normal periradicular group were having a third molar extracted (vs. approximately 20% in each of the irreversible pulpitis groups), and previous studies have shown that approximately 78% of patients presenting for third molar extraction have experienced a prior episode of pericoronitis (5). We note that the mean age for the normal pulp/normal periradicular group is significantly
Figure 3. Diagrammatic representation of hypothesis 1 (mechanical allodynia because of pulpal mechanoreceptive neurons). Carious lesion allows bacteria and bacterial byproducts access to pulp tissue. Inflammation develops causing activation of pulpal mechanoreceptors, by bacterial byproducts and inflammatory mediators and subsequent mechanical allodynia.
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JOE — Volume 33, Number 5, May 2007
Clinical Research
Figure 4. Diagrammatic representation of hypothesis 2 (mechanical allodynia because of activation of periradicular mechanoreceptive neurons). Inflammation develops in coronal portion of the pulp as in hypothesis 1. Inflammatory mediators and bacterial byproducts diffuse apically into periradicular tissues causing inflammation, activation of periradicular mechanoreceptors, and subsequent mechanical allodynia.
lower than the irreversible pulpitis groups (p ⬍ 0.001), a finding that is consistent with younger patients undergoing third molar extractions. The traditional model of irreversible pulpitis consists of a localized inflammatory response to bacterial infection of the pulp-dentin complex that eventually leads to formation of a localized abscess and subsequent pulpal necrosis. Thermal hyperalgesia (increased pain responses to a noxious thermal stimulus) or thermal allodynia (pain response from a nonnoxious thermal stimulus) are hallmark features of irreversible pulpitis (2). However, comparatively few studies have characterized the coexpression of mechanical allodynia. In this study population, we have documented that mechanical allodynia occurs frequently in teeth with irreversible pulpitis and significantly predicts that subset of patients experiencing the greatest levels of current and past pain. Because the presence of preoperative pain is a strong risk factor for posttreatment pain (6, 7), recognition of the predictive value of mechanical allodynia in these patients for appropriate postoperative pain control has strong clinical implications. Although the hypothesis of pain caused by irreversible pulpitis focuses on pulpal nociceptive mechanisms, the large subset of patients with mechanical allodynia suggests that alternative pain mechanisms might contribute to this form of odontalgia. At least three hypotheses might contribute to the concurrent presentation of mechanical allodynia with irreversible pulpitis: (1) activation of pulpal mechanoreceptive nociceptive neurons mediate mechanical allodynia (Fig. 3); (2) inflammatory mediators or bacterial byproducts diffuse into the periradicular space before pulpal necrosis, leading to activation of periradicular mechanoreceptive nociceptive neurons (Fig. 4); and/or (3) activation of pulpal nociceptors evokes mechanical allodynia via central sensitization (Fig. 5).
JOE — Volume 33, Number 5, May 2007
The first hypothesis proposes that pulpal mechanoreceptive nociceptors mediate the development of mechanical allodynia. Although pulpal afferent neurons are not traditionally viewed as having proprioceptive functions, there appears to be at least some degree of pulpal innervation by mechanoreceptive neurons. Preclinical research has demonstrated that most pulpal afferent A-fibers respond to mechanical stimulation of the pulp tissue with von Frey hairs (8). These findings were replicated in another preclinical model that showed that certain pulpal afferent neurons were stimulated by mechanical transients applied to intact enamel (9). In addition, the hydrodynamic theory of dentinal pain proposes that fluid movement is detected by presumably mechanoreceptive nociceptors innervating dentinal tubules (10). A preliminary clinical trial has also shown that teeth containing vital pulp tissue were able to detect mechanical loads at twice the level of sensitivity as root filled teeth (11), a finding that is consistent with mechanoreceptors being present in human dental pulp. However, if pulpal mechanoreceptive neurons become sensitized during pulpal inflammation, it is unclear why this would not occur in all patients with irreversible pulpitis, particularly because inflammatory mediator levels are, by definition, sufficient to evoke thermal allodynia or thermal hyperalgesia as indicated by the results of the clinical thermal testing with Endo-Ice. Thus, the present data do not provide strong support for this hypothesis. A second hypothesis is that pulpally derived inflammatory mediators and/or bacterial byproducts present in the inflamed human pulp (12) diffuse into the periradicular space preceding complete pulpal necrosis causing an inflammatory response before radiographically evident bone resorption (13), thereby locally activating mechanoreceptive nociceptors innervating the periodontal ligament. Bacterial infec-
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Clinical Research
Figure 5. Diagrammatic representation of hypothesis 3 (mechanical allodynia because of central sensitization). Bacterial byproducts and inflammatory mediators activate nociceptors on pulpal nociceptive neurons. This afferent barrage causes central sensitization in the medullary dorsal horn leading to rapid expansion of the receptive fields leading to the development of mechanical allodynia at distant sites.
tion of the pulp appears to be absolutely necessary for the development of periapical inflammation (14, 15) in teeth without a recent history of acute trauma. This hypothesis is strengthened by the finding that histologic changes in periradicular tissue organization can be detected before total pulpal necrosis (16) and that vital inflamed tissue can exist in the apical third of teeth with periradicular radiolucencies (17). More than half of the patients with a vital inflamed pulp in the current study were clinically diagnosed with acute periradicular periodontitis. This may indicate that periradicular inflammation is an early manifestation of the pulpal inflammatory process and that a relatively large percentage of patients with irreversible pulpitis and normal periradicular tissues will progress to having irreversible pulpitis with acute periradicular periodontitis if they do not seek treatment. Thus, our data are consistent with preclinical and clinical research supporting this hypothesis. A third possibility is that activation of pulpal nociceptors evokes mechanical allodynia via central sensitization independent of any local activation of periradicular nociceptors. Evidence favoring this latter hypothesis emerges from preclinical studies showing that even brief activation of pulpal neurons expressing the transient receptor potential subtype A1 (TRPA1) by mustard oil leads to a profound mechanical allodynia at distant sites. The mustard oil induced barrage of nociceptive inputs to the medullary dorsal horn results in abundant release of glutamate and neuropeptides producing a robust central sensitization (18, 19). Importantly, this preclinical study showed that activation of pulpal nociceptors produced a rapid expansion of receptive fields of medullary dorsal horn neurons leading to increased mechanical sensitivity at distant sites (18), suggesting that this effect does not require chronic periods of sensitization, but can occur soon after sufficient stimulation of pulpal nociceptors. In the present study, we note that patients with greater levels of spontaneous pain (presumably because of activation of pulpal nociceptors) reported significantly greater levels of mechanical allodynia. Thus, our data are consistent with central sensitization mechanisms occurring in patients with irreversible pulpitis. In conclusion, the major findings of this study are that more than 50% of patients diagnosed with irreversible pulpitis in a community dental clinic presented with mechanical allodynia, and this was associated with significantly greater levels of past and present pain. The presence of mechanical allodynia with preoperative pain should be considered in developing an appropriate postoperative pain management plan. Moreover, these data suggest that the traditional model of pulpitis pain should be modified to explain the large incidence of periradicular mechanical allodynia. Three alternative hypotheses are advanced, and prospective clinical trials should be conducted to evaluate these alternative models of odontalgia.
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Acknowledgments * Christopher B. Owatz and Asma A. Khan contributed equally to this article. The authors wish to thank Erin Locke, BSN for her assistance in collecting this data.
References 1. Lipton JA, Ship JA, Larach-Robinson D. Estimated prevalence and distribution of reported orofacial pain in the United States. J Am Dent Assoc 1993;124:115–21. 2. Klausen B, Helbo M, Dabelsteen E. A differential diagnostic approach to the symptomatology of acute dental pain. Oral Surg Oral Med Oral Pathol 1985;59:297–301. 3. Keenan JV, Farman AG, Fedorowicz Z, Newton JT. A Cochrane systematic review finds no evidence to support the use of antibiotics for pain relief in irreversible pulpitis. J Endod 2006;32:87–92. 4. Byers MR, Narhi MV. Dental injury models: experimental tools for understanding neuroinflammatory interactions and polymodal nociceptor functions. Crit Rev Oral Biol Med 1999;10:4 –39. 5. McGrath C, Comfort MB, Lo EC, Luo Y. Can third molar surgery improve quality of life? A 6-month cohort study. J Oral Maxillofac Surg 2003;61:759 – 63. 6. Torabinejad M, Cymerman JJ, Frankson M, Lemon RR, Maggio JD, Schilder H. Effectiveness of various medications on postoperative pain following complete instrumentation. J Endod 1994;20:345–54. 7. O’Keefe EM. Pain in endodontic therapy: preliminary study. J Endod 1976;2:315–9. 8. Narhi MV. The characteristics of intradental sensory units and their responses to stimulation. J Dent Res 1985;64:564 –71. 9. Dong WK, Chudler EH, Martin RF. Physiological properties of intradental mechanoreceptors. Brain Res 1985;334:389 –95. 10. Brannstrom M, Astrom A. The hydrodynamics of the dentine; its possible relationship to dentinal pain. Int Dent J 1972;22:219 –27. 11. Randow K, Glantz PO. On cantilever loading of vital and non-vital teeth. An experimental clinical study. Acta Odontol Scand 1986;44:271–7. 12. D’Souza R, Brown LR, Newland JR, Levy BM, Lachman LB. Detection and characterization of interleukin-1 in human dental pulps. Arch Oral Biol 1989;34:307–13. 13. Stashenko P, Dewhirst FE, Peros WJ, Kent RL, Ago JM. Synergistic interactions between interleukin 1, tumor necrosis factor, and lymphotoxin in bone resorption. J Immunol 1987;138:1464 – 8. 14. Kakehashi S, Stanley HR, Fitzgerald RJ. The effects of surgical exposures of dental pulps in germ-free and conventional laboratory rats. Oral Surg Oral Med Oral Pathol 1965;20:340 –9. 15. Moller AJ, Fabricius L, Dahlen G, Ohman AE, Heyden G. Influence on periapical tissues of indigenous oral bacteria and necrotic pulp tissue in monkeys. Scand J Dent Res 1981;89:475– 84. 16. Stashenko P, Wang CY, Riley E, Wu Y, Ostroff G, Niederman R. Reduction of infectionstimulated periapical bone resorption by the biological response modifier PGG glucan. J Dent Res 1995;74:323–30. 17. Ricucci D, Pascon EA, Ford TR, Langeland K. Epithelium and bacteria in periapical lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;101:239–49. 18. Chiang CY, Zhang S, Xie YF, et al. Endogenous ATP involvement in mustard-oilinduced central sensitization in trigeminal subnucleus caudalis (medullary dorsal horn). J Neurophysiol 2005;94:1751– 60. 19. Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science 2000;288:1765–9.
JOE — Volume 33, Number 5, May 2007
The Incidence of Mechanical Allodynia in Patients With Irreversible Pulpitis Christopher B. Owatz, DMD,* Asma A. Khan, BDS, PhD,* William G. Schindler, DDS, MS, Scott A. Schwartz, DDS, Karl Keiser, DDS, MS, and Kenneth M. Hargreaves, DDS, PhD Abstract The mechanisms of odontogenic pain are complex and incompletely understood. Cases of irreversible pulpitis are thought to represent a localized inflammatory response to bacterial challenge in dental pulp tissue. The presenting symptoms are classically defined by exaggerated painful episodes to thermal stimuli that may linger after cessation of the stimulus. However, the associated incidence of mechanical allodynia, defined as reduced mechanical pain threshold to masticatory forces, has not been characterized. This study evaluated pain intensity ratings and the presence of mechanical allodynia reported by 993 consecutive dental patients presenting for tooth extraction in a community health center. After clinical and radiographic examinations, the pulpal/periradicular diagnostic categories were normal pulp/normal periradicular (n ⫽ 792 patients), irreversible pulpitis/normal periradicular (n ⫽ 86), or irreversible pulpitis/acute periradicular periodontitis (n ⫽ 115). The rank order for the mean values of pain intensity ratings was irreversible pulpitis/acute periradicular periodontitis ⬎ irreversible pulpitis/normal periradicular ⬎ normal/normal (p ⬍ 0.05 for all comparisons). The incidence of mechanical allodynia in patients presenting with irreversible pulpitis was 57.2%, indicating that periradicular mechanical allodynia contributes to early stages of odontogenic pain because of inflammation of vital pulpal tissue. (J Endod 2007;33:552–558)
Key Words Acute periradicular periodontitis, incidence, irreversible pulpitis, mechanical allodynia, pain
From the Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, Texas. Supported in part by P01 DA16719 (KMH), R01 NS45186 (KMH), and K23 DE14864 (AAK). Address requests for reprints to Dr. Christopher B. Owatz, University of Texas Health Science Center at San Antonio, Department of Endodontics, MC 7892, 7703 Floyd Curl Dr, San Antonio, TX 78229. E-mail address: [email protected]. 0099-2399/$0 - see front matter Copyright © 2007 by the American Association of Endodontists. doi:10.1016/j.joen.2007.01.023
552
Owatz et al.
O
rofacial pain is very common among the general population. A survey of noninstitutionalized civilian residents of the United States showed that 28% of the population reported experiencing orofacial pain in the preceding 6 months, with the most common report being odontalgia (1). Odontogenic pain can be caused by activation of pulpal or periradicular nociceptors. There are two hallmark features of many clinical pain conditions: Allodynia is defined as a reduction in pain threshold, whereby pain occurs in response to innocuous mechanical or thermal stimulation. Conversely, hyperalgesia is defined as an increased or exaggerated responsiveness to normally noxious mechanical or thermal stimuli. Both of these features are evaluated in endodontic clinical testing. Mechanical allodynia is typically evaluated by a percussion test and a response is deemed positive if this innocuous tapping produces a sensation of pain. Thermal hyperalgesia is generally evaluated by application of a cold stimulus that is sufficient to produce a transient and slight sensation of pain in a control tooth but evokes a prolonged or intense sensation of pain when applied to a tooth with irreversible pulpitis. Clinical research (2) indicates that the presentation of thermal hyperalgesia is primarily mediated by pulpal nociceptive mechanisms (odds ratio, 9.0), whereas mechanical allodynia is primarily mediated by periradicular nociceptive mechanisms (odds ratio, 6.9). Irreversible pulpitis generally originates as a localized inflammatory response to bacterial invasion of the pulp-dentin complex. It is speculated that irreversible pulpitis, often characterized by brief, intense painful episodes to thermal stimuli that linger after cessation of the stimulus, is one of the most frequent reasons that patients seek emergency dental care (3). The mechanisms for this pain are thought to be caused by sensitization and activation of pulpal nociceptors because of local release of inflammatory mediators (4). However, this model does not explain why periradicular mechanical allodynia would be present in these patients. To begin to identify mechanisms and resultant signs and symptoms of odontogenic pain, we have characterized thermal and mechanical allodynia in a group of 993 patients presenting for tooth extraction at a local community health center.
Materials and Methods The Institutional Review Board of the University of Texas Health Science Center at San Antonio approved this study, and the informed consent of all human subjects who participated in the investigation was obtained. Patients experiencing odontogenic pain and/or presenting for dental extractions at the University Health Center Downtown Facility, University of Texas Health Science Center at San Antonio were invited to participate. Patients were excluded if they were unable or unwilling to provide informed consent. Information was recorded regarding the patient’s ethnicity, sex, age and tooth number for which they were seeking emergency treatment. Patients used validated pain intensity scales to rate both their current level of spontaneous pain and their recalled level of “worst pain ever.” The spontaneous pain was described to the patient as pain without stimulation on the day of their appointment, and their “worst pain ever” was described to the patient as the most intense pain they had ever experienced associated with the tooth to be treated. The patients rated their spontaneous and worst pain ever pain intensity on a four-point category scale (none, mild, moderate, and severe) and the 100-mm visual analog scale (VAS). One examiner determined the pulpal and periradicular diagnoses of all patients. To determine the pulpal status, a 6-inch cotton tipped applicator was saturated with
JOE — Volume 33, Number 5, May 2007
Clinical Research TABLE 1. Mean age, sex, and ethnic distribution of dental patients Pulpal and Periradicular Diagnosis Normal pulp/ normal periradicular Irreversible pulpitis/ normal periradicular Irreversible pulpitis/ acute periradicular periodontitis All subjects
Sex
Ethnicity
n
Mean Age
Male
Female
Hispanic
Black
White
Asian
Other
792
32.6
34% (268)
66% (524)
60.2% (477)
9.0% (71)
27.9% (221)
2.5% (20)
0.4% (3)
86
42.6
44% (38)
56% (48)
62.8% (54)
30.2% (26)
7.0% (6)
0.0% (0)
0.0% (0)
115
43.6
37% (43)
63% (72)
59.1% (68)
9.6% (11)
28.7% (33)
1.7% (2)
0.9% (1)
993
34.7
35% (349)
65% (644)
60.3% (599)
10.9% (108)
26.2% (260)
2.2% (22)
0.4% (4)
TABLE 2. Distribution by tooth type: percentage (number) Pulpal and Periradicular Diagnosis Normal/normal (792) Irreversible pulpitis/ normal (86) Irreversible pulpitis/ acute periradicular periodontitis (115)
Maxillary Anteriors
Mandibular Anteriors
Maxillary Premolars
Mandibular Premolars
Maxillary First and Second Molars
Mandibular First and Second Molars
Maxillary Third Molars
Mandibular Third Molars
2.8% (22) 8.1% (7)
8.7% (69) 8.1% (7)
1.6% (13) 11.6% (10)
5.3% (42) 4.7% (4)
2.8% (22) 30.2% (26)
2.8% (22) 17.4% (15)
39.1% (310) 8.1% (7)
36.9% (292) 11.6% (10)
8.7% (10)
3.5% (4)
16.5% (19)
8.7% (10)
26.1% (30)
16.5% (19)
13.0% (15)
7.0% (8)
Endo-Ice refrigerant spray (Coltène/Whaledent, Cuyahoga Falls, OH) and applied first to a control tooth (contralateral side) and then to the tooth in question. A diagnosis of a normal pulp occurred when the patient felt a cold sensation that subsided once the stimulus was removed, and a diagnosis of irreversible pulpitis occurred when the patient reported an exaggerated response to the cold sensation that lingered as a dull ache once the stimulus was removed. Patients with a diagnosis of pulpal necrosis were not included in this study. To determine the periradicular status, the examiner first percussed a control tooth (contralateral side) by using the handle of a mouth mirror and then the tooth in question. A diagnosis of a normal periradicular tissue occurred when the percussed tooth was not tender (similar sensation as the control tooth), and a diagnosis of acute periradicular periodontitis occurred when the patient reported tenderness to percussion. All patients included in this study had either normal periradicular radiographic anatomy or no more than a 2-fold widening of the periodontal ligament space. Mean spontaneous pain and “worst pain ever” pain intensity ratings were calculated for each of the following three groups: (1) normal pulp and normal periradicular tissues, (2) irreversible pulpitis and normal periradicular tissues, and (3) irreversible pulpitis and acute periradicular periodontitis. The data are presented as mean value ⫾ standard error of the mean (SEM) and were analyzed by using a oneway analysis of variance (ANOVA) and Tukey post hoc test. A difference was considered significant at p ⬍ 0.05.
and thus by definition were considered to have mechanical allodynia; this criterion was used to subdivide these patients into a group having normal periradicular tissue and a group having acute periradicular periodontitis. As shown in Figure 1, the spontaneous pain intensity reported by the patient on the day of the dental appointment differed significantly among patients diagnosed with normal pulp and normal periradicular tissue (8.1 ⫾ 0.8 mm VAS), irreversible pulpitis with normal periradicular tissue (25.3 ⫾ 3.4 mm VAS), and irreversible pulpitis with acute periradicular periodontitis (44.0 ⫾ 3.2 mm VAS). Analysis of the results from the category pain scale for spontaneous pain data showed a similar trend to the 100-mm VAS data. The weighted mean values were 0.26 for normal pulp and normal periradicular tissue, 0.76 for irreversible pulpitis and normal periradicular tissue, and 1.51 for irreversible pulpitis and acute periradicular periodontitis.
Results There were 993 subjects included in the study. Table 1 summarizes the mean age and the sex and ethnic distribution for each of the three diagnostic groups. The patient distribution by tooth type is displayed in Table 2. There were no significant differences among the three groups for any of the variables except for mean age and percentage of third molars. The normal pulp/normal periradicular group was significantly different from the irreversible pulpitis/normal periradicular and the irreversible pulpitis/acute periradicular periodontitis groups for these variables (p ⬍ 0.001); the latter two groups were not significantly different from each other. Of the 201 patients diagnosed with irreversible pulpitis, 57.2% had concomitant acute periradicular periodontitis
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Figure 1. Spontaneous pain intensity experienced by the patient on the day of data collection, reported on the 100-mm VAS, presented as mean values ⫾ SEM. Differences between all groups were statistically significant when analyzed with the one-way ANOVA and Tukey post hoc test (**p ⬍ 0.001).
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Discussion
Figure 2. Worst pain ever pain intensity experienced by the patient, reported on the 100 mm VAS, presented as mean values ⫾ SEM. Differences between all groups were statistically significant when analyzed with the one-way ANOVA and Tukey post hoc test (**p ⬍ 0.001, *p ⬍ 0.05).
Figure 2 presents the “worst pain ever” pain intensity reported by the patient on the day of the dental appointment. These pain values differed significantly among patients diagnosed with normal pulp and normal periradicular tissue (41.1 ⫾ 1.4 mm VAS), irreversible pulpitis with normal periradicular tissue (70.0 ⫾ 3.8 mm VAS), and irreversible pulpitis with acute periradicular periodontitis (85.4 ⫾ 1.6 mm VAS). Analysis of the results from the category pain scale for “worst pain ever” pain intensity data showed a similar trend to the 100-mm VAS
In this study, we examined the incidence of mechanical allodynia among dental patients presenting with odontalgia and/or an indication for tooth extraction. These patients also rated their spontaneous and “worst pain ever” pain intensity to determine if mechanical allodynia occurred more frequently in patients with increased reported pain levels. Our results show that ⬎50% of the patients diagnosed with irreversible pulpitis were also diagnosed with mechanical allodynia. In addition, patients diagnosed with irreversible pulpitis and mechanical allodynia rated their spontaneous and “worst pain ever” pain intensity as significantly greater than those patients with irreversible pulpitis and normal periradicular tissues. Although patients with normal pulpal and periradicular diagnoses would be expected to report no pain, they might have a history of pain from a prior exacerbation of periodontal disease, an episode of pericoronitis, or another inflammatory condition. Seventy-six percent of the subjects in the normal pulp and normal periradicular group were having a third molar extracted (vs. approximately 20% in each of the irreversible pulpitis groups), and previous studies have shown that approximately 78% of patients presenting for third molar extraction have experienced a prior episode of pericoronitis (5). We note that the mean age for the normal pulp/normal periradicular group is significantly
Figure 3. Diagrammatic representation of hypothesis 1 (mechanical allodynia because of pulpal mechanoreceptive neurons). Carious lesion allows bacteria and bacterial byproducts access to pulp tissue. Inflammation develops causing activation of pulpal mechanoreceptors, by bacterial byproducts and inflammatory mediators and subsequent mechanical allodynia.
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Figure 4. Diagrammatic representation of hypothesis 2 (mechanical allodynia because of activation of periradicular mechanoreceptive neurons). Inflammation develops in coronal portion of the pulp as in hypothesis 1. Inflammatory mediators and bacterial byproducts diffuse apically into periradicular tissues causing inflammation, activation of periradicular mechanoreceptors, and subsequent mechanical allodynia.
lower than the irreversible pulpitis groups (p ⬍ 0.001), a finding that is consistent with younger patients undergoing third molar extractions. The traditional model of irreversible pulpitis consists of a localized inflammatory response to bacterial infection of the pulp-dentin complex that eventually leads to formation of a localized abscess and subsequent pulpal necrosis. Thermal hyperalgesia (increased pain responses to a noxious thermal stimulus) or thermal allodynia (pain response from a nonnoxious thermal stimulus) are hallmark features of irreversible pulpitis (2). However, comparatively few studies have characterized the coexpression of mechanical allodynia. In this study population, we have documented that mechanical allodynia occurs frequently in teeth with irreversible pulpitis and significantly predicts that subset of patients experiencing the greatest levels of current and past pain. Because the presence of preoperative pain is a strong risk factor for posttreatment pain (6, 7), recognition of the predictive value of mechanical allodynia in these patients for appropriate postoperative pain control has strong clinical implications. Although the hypothesis of pain caused by irreversible pulpitis focuses on pulpal nociceptive mechanisms, the large subset of patients with mechanical allodynia suggests that alternative pain mechanisms might contribute to this form of odontalgia. At least three hypotheses might contribute to the concurrent presentation of mechanical allodynia with irreversible pulpitis: (1) activation of pulpal mechanoreceptive nociceptive neurons mediate mechanical allodynia (Fig. 3); (2) inflammatory mediators or bacterial byproducts diffuse into the periradicular space before pulpal necrosis, leading to activation of periradicular mechanoreceptive nociceptive neurons (Fig. 4); and/or (3) activation of pulpal nociceptors evokes mechanical allodynia via central sensitization (Fig. 5).
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The first hypothesis proposes that pulpal mechanoreceptive nociceptors mediate the development of mechanical allodynia. Although pulpal afferent neurons are not traditionally viewed as having proprioceptive functions, there appears to be at least some degree of pulpal innervation by mechanoreceptive neurons. Preclinical research has demonstrated that most pulpal afferent A-fibers respond to mechanical stimulation of the pulp tissue with von Frey hairs (8). These findings were replicated in another preclinical model that showed that certain pulpal afferent neurons were stimulated by mechanical transients applied to intact enamel (9). In addition, the hydrodynamic theory of dentinal pain proposes that fluid movement is detected by presumably mechanoreceptive nociceptors innervating dentinal tubules (10). A preliminary clinical trial has also shown that teeth containing vital pulp tissue were able to detect mechanical loads at twice the level of sensitivity as root filled teeth (11), a finding that is consistent with mechanoreceptors being present in human dental pulp. However, if pulpal mechanoreceptive neurons become sensitized during pulpal inflammation, it is unclear why this would not occur in all patients with irreversible pulpitis, particularly because inflammatory mediator levels are, by definition, sufficient to evoke thermal allodynia or thermal hyperalgesia as indicated by the results of the clinical thermal testing with Endo-Ice. Thus, the present data do not provide strong support for this hypothesis. A second hypothesis is that pulpally derived inflammatory mediators and/or bacterial byproducts present in the inflamed human pulp (12) diffuse into the periradicular space preceding complete pulpal necrosis causing an inflammatory response before radiographically evident bone resorption (13), thereby locally activating mechanoreceptive nociceptors innervating the periodontal ligament. Bacterial infec-
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Figure 5. Diagrammatic representation of hypothesis 3 (mechanical allodynia because of central sensitization). Bacterial byproducts and inflammatory mediators activate nociceptors on pulpal nociceptive neurons. This afferent barrage causes central sensitization in the medullary dorsal horn leading to rapid expansion of the receptive fields leading to the development of mechanical allodynia at distant sites.
tion of the pulp appears to be absolutely necessary for the development of periapical inflammation (14, 15) in teeth without a recent history of acute trauma. This hypothesis is strengthened by the finding that histologic changes in periradicular tissue organization can be detected before total pulpal necrosis (16) and that vital inflamed tissue can exist in the apical third of teeth with periradicular radiolucencies (17). More than half of the patients with a vital inflamed pulp in the current study were clinically diagnosed with acute periradicular periodontitis. This may indicate that periradicular inflammation is an early manifestation of the pulpal inflammatory process and that a relatively large percentage of patients with irreversible pulpitis and normal periradicular tissues will progress to having irreversible pulpitis with acute periradicular periodontitis if they do not seek treatment. Thus, our data are consistent with preclinical and clinical research supporting this hypothesis. A third possibility is that activation of pulpal nociceptors evokes mechanical allodynia via central sensitization independent of any local activation of periradicular nociceptors. Evidence favoring this latter hypothesis emerges from preclinical studies showing that even brief activation of pulpal neurons expressing the transient receptor potential subtype A1 (TRPA1) by mustard oil leads to a profound mechanical allodynia at distant sites. The mustard oil induced barrage of nociceptive inputs to the medullary dorsal horn results in abundant release of glutamate and neuropeptides producing a robust central sensitization (18, 19). Importantly, this preclinical study showed that activation of pulpal nociceptors produced a rapid expansion of receptive fields of medullary dorsal horn neurons leading to increased mechanical sensitivity at distant sites (18), suggesting that this effect does not require chronic periods of sensitization, but can occur soon after sufficient stimulation of pulpal nociceptors. In the present study, we note that patients with greater levels of spontaneous pain (presumably because of activation of pulpal nociceptors) reported significantly greater levels of mechanical allodynia. Thus, our data are consistent with central sensitization mechanisms occurring in patients with irreversible pulpitis. In conclusion, the major findings of this study are that more than 50% of patients diagnosed with irreversible pulpitis in a community dental clinic presented with mechanical allodynia, and this was associated with significantly greater levels of past and present pain. The presence of mechanical allodynia with preoperative pain should be considered in developing an appropriate postoperative pain management plan. Moreover, these data suggest that the traditional model of pulpitis pain should be modified to explain the large incidence of periradicular mechanical allodynia. Three alternative hypotheses are advanced, and prospective clinical trials should be conducted to evaluate these alternative models of odontalgia.
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Acknowledgments * Christopher B. Owatz and Asma A. Khan contributed equally to this article. The authors wish to thank Erin Locke, BSN for her assistance in collecting this data.
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