- Email: [email protected]
Neuropathic pain in the orofacial region: The role of pain history. A retrospective study
J Stomatol Oral Maxillofac Surg 118 (2017) 147–150
Available online at
ScienceDirect www.sciencedirect.com
Original Article
Neuropathic pain in the orofacial region: The role of pain history. A retrospective study W. Dieb a, N. Moreau b, I. Chemla a, V. Descroix a, Y. Boucher a,* a b
UFR d’Odontologie, Universite´ Paris Diderot, Hoˆpital Pitie´ Salpeˆtrie`re, Paris, France UFR d’Odontologie, Universite´ Paris Descartes, Hoˆpital Bretonneau, Paris, France
A R T I C L E I N F O
A B S T R A C T
Article history: Received 6 September 2016 Accepted 16 March 2017 Available online 29 March 2017
Introduction: Orofacial neuropathic pain is often difficult to treat, mostly because of still unclear underlying mechanisms. The occurrence of such neuropathic pain varies depending on different factors, of which preexisting preoperative pain seems to be of high importance. The aim of this study was thus to test the hypothesis that prior history of pain could indeed be considered a risk factor for the development of orofacial neuropathic pain in the same region. Methods: The study was performed in the dental department of the Groupe Hospitalier Pitie´-Salpeˆtrie`re (GHPS) in Paris, France. We investigated the presence of prior inflammatory pain before development of orofacial neuropathic pain in 56 patients. For each patient file, the following items were collected: age, gender; medical history; diagnosis; description of the pain (at time of consultation); presence or absence of prior dental treatment; date and type of dental treatment received. Results: 41 patients (73%) of orofacial neuropathic pain patients had a history of pain compatible with an inflammatory condition; 4% (n = 2) did not report any prior pain and 23% (n = 13) could not remember. Among the patients with documented history of pain prior to neuropathy, 88% (n = 36) received surgical treatment; 61%, (n = 25) endodontic treatment and 22%, (n = 9) restorative treatment. All eventually received endodontic treatment or tooth extraction. These dental treatments are compatible with the hypothesis of prior inflammatory pain in these patients. Conclusion: These results support the hypothesis that prior inflammatory pain could favor the development of orofacial neuropathic pain. Prevention and treatment of inflammatory trigeminal pain may therefore play a key role in preventing future neuropathic pain development.
C 2017 Elsevier Masson SAS. All rights reserved.
Keywords: Trigeminal Neuropathic pain Priming Inflammation Endodontics
1. Introduction Post-traumatic neuropathic pain is a chronic condition difficult to endure and to treat, especially trigeminal neuropathic pain which is specific in its pathophysiology [1,2] and available treatments [3] as compared to its spinal counterpart. The prevalence of this painful condition ranges from 0.5% to 12% following oral surgery, including orthograde endodontic treatments (ET) as well as retrograde surgical endodontic treatments, dental extractions, cystic enucleations, orthognathic surgery or dental implants and may vary according to different factors, among which age, gender, importance of nerve damage, type of surgery, surgical technique and the presence of preoperative pain [4]. Regarding the latter, most common dental pains (resulting from caries and periodontal diseases) are caused by microorganisms
* Corresponding author at: UFR d’Odontologie, 5, rue Garancie`re, 75006 Paris, France. E-mail address: [email protected] (Y. Boucher). http://dx.doi.org/10.1016/j.jormas.2017.03.004 C 2017 Elsevier Masson SAS. All rights reserved. 2468-7855/
triggering inflammatory reactions and exposing primary afferent neurons to algogenic substances. Some of these molecules are known to drive phenotypic and functional changes in nerve and surrounding glial, immune and vascular cells [5,6]. It can therefore be hypothesized that nerve trauma occurring in an inflammatory environment might favor the onset of neuropathic pain. The aim of this study was to test this hypothesis from a clinical standpoint. In a retrospective analysis of a sample of patients diagnosed with orofacial neuropathic pain, we investigated the evidence in favor of a history of pain resulting from local inflammatory conditions prior to surgical trauma. 2. Methods and patients 2.1. Sample The study was performed in the dental department of the Groupe Hospitalier Pitie´-Salpeˆtrie`re (GHPS) in Paris, France. Medical files of patients who attended the chronic orofacial pain
148
W. Dieb et al. / J Stomatol Oral Maxillofac Surg 118 (2017) 147–150
consultation, within a secondary/tertiary referral center, between 09/03/2012 and 12/19/2014 were retrieved from the hospital database and analyzed. The study was approved by the board of the dental department. Authorization for retrieval and use of patient data was obtained from the Commission Nationale de l’Informatique et des Liberte´s (CNIL) (#1839648). 2.2. Consultation and diagnosis All consultations were performed by the same trained experienced senior practitioner (YB) according to a previously described methodology [7]. This standard examination included (1) detailed medical history including medications, pain comorbidities, history of spinal/cranial traumatic events, psychological status, gross cranial nerve functional assessment; (2) specific pain history and characteristics including time course, quality, associate autonomic signs, interference with sleep; (3) extraoral clinical evaluation including TMJ, masticatory and neck muscles assessment; (4) intraoral examination including mechanical/thermal/ electrical tooth sensitivity tests, oral mucosa and soft tissues examination including testing for hypoesthesia/hyperesthesia with the use of a sharp and blunt stimulus, static and mechanical allodynia using digital pressure rubbing of the painful areas, compared with the contralateral sites and (5) relevant dental and/ or facial imagery. Quality of endodontic treatments was evaluated radiographically using standard X-rays or cone beam computed tomography CBCT in doubtful cases. Patients were referred to other medical specialists (neurologist, ENT specialist, etc.) when needed. 2.3. Exclusion and inclusion criteria Patients diagnosed with definitive orofacial neuropathic pain, according to the criteria of Benoliel et al. [4], were included in the study, i.e. satisfying criteria A B C D and E: (A) spontaneous or touchevoked (stimulus dependent) pain predominantly affecting the receptive field of one or more divisions of the trigeminal nerve. Duration ranges widely from episodic (minutes to days) and may also be constant; (B) develops within 3 months of an identifiable traumatic event to the painful area or relevant innervation; continues for more than 3 months; (C) at least one clinically evident neurological dysfunction: positive sign (hyperalgesia/allodynia/ swelling or flushing) and/or: negative sign anesthesia/hypoesthesia; (D) imaging or neurophysiology demonstrating a neurological lesion and its location. Endodontic treatments or avulsions were taken as evidence as nerve lesion – no neurophysiologic evaluation, like Quantitative Sensory Testing (QST) or evoked potentials, was performed in this study; (E) not attributed to another disorder. For each neuropathic pain patient file, the following items were collected: age, gender; medical history; diagnosis; description of the pain including location, presence of DN4 neuropathic pain questionnaire items, i.e. burning/tingling/numbness/electrical shocks/allodynia; increase or not during the day; Visual Analog Scale (VAS) score; history of pain (presence/absence and date of prior dental treatments); date and type of dental treatment (restorative, endodontic or surgical). Data was transcripted on an Excel spreadsheet (MicrosoftTM) and anonymized before analysis.
Fig. 1. Distribution of the sample according to age. Total range was 31–89.
54.0 14.4 years old. Only 13% of patients did not present any significant health issue. The majority had one or more comorbidities which were mostly: osteoarthritis (21%; n = 12), headache (18%; n = 10), hypertension (18%; n = 10) or history of trauma (whiplash, falls, blows, etc.) (11%; n = 6). 82% of patients (n = 46) had at least one chronic condition (hepatitis, diabetes, high cholesterol, etc.) prior to consultation. In addition, 27% of patients (n = 15) reported chronic stress (resulting from severe family or professional issues, etc.) and 23% (n = 13) had documented psychological/psychiatric background (depression, schizophrenia, etc.); 37.5% of patients (n = 21) combined both chronic stress and psychological/psychiatric ailments. Characteristics of the pain: Pain location from the different cases is summarized in Fig. 2. In some cases, simultaneous pain in multiple locations was described. Most commonly cited descriptors of the pain (Fig. 3) adhered with classical neuropathic pain descriptors although 88% of patients (n = 49) expressed atypical complaints (swelling sensation, tingling, etc.). Mechanical allodynia was present in 34% of cases (n = 19). History of prior pain: About two-thirds of patients from the sample (73%; n = 41), reported prior episodes of pain before being diagnosed with orofacial neuropathic pain, 4% (n = 2) did not report any prior pain and 23% (n = 13) could not remember (Fig. 4). Among these 41 patients who were identified as having a painful history prior to neuropathy, dental treatments received prior to the onset of neuropathic pain were, in order of decreasing frequency:
3. Results 268 records of patients attending the pain consultation were identified in the database. Among them, 229 could be retrieved and 56 cases were classified as orofacial neuropathic pain. This group constituted the sample, which comprised 6 men (11%) and 50 women (89%; 55% of which were menopaused). Age of patients ranged from 32 to 89 years (Fig. 1) with a mean age of
Fig. 2. Main localization of pain symptoms. One patient could also experience several localizations.
W. Dieb et al. / J Stomatol Oral Maxillofac Surg 118 (2017) 147–150
149
4. Discussion
Fig. 3. Main characteristics of the pain reported by the patient or assessed by the examiner.
Fig. 4. Distribution of patients according to the history of pain prior to the diagnosis of orofacial neuropathic pain (ET = endodontic treatment). See text for details.
(1) surgical treatments (88%; n = 36) which consisted of extractions, cystic enucleation or endodontic surgery; (2) endodontic treatments (ET) (61%; n = 25); (3) restorative treatments (22%; n = 9). All patients with restorative treatments eventually received endodontic treatment or tooth extraction. Only 2 patients (4%) from this group did not receive any of these three types of treatments. One of the two patients claimed that his (neuropathic) pain appeared after painful gingival inflammation caused by an overextended crown margin; the second remembered having a different type of pain prior to the most recent painful episodes that motivated his last consultation, without being able to remember the cause of such previous pain.
The general characteristics of this sample are in accordance with those from other studies of neuropathic facial pains, i.e. mostly menopausal women with psychological distress and frequent comorbidities. No preferential localization was found in our sample which is not in accordance with another study [8] reporting neuropathic pain preferentially located on the maxillae. The main result of this study is that almost 3/4 of the patients (73%) with a diagnosis of orofacial neuropathic pain reported pain in a tooth or gingiva prior to the dental treatment-related nerve lesion and almost all of these (95%; 39 out of 41) received prior dental treatment compatible with a diagnosis of an inflammatory disease. This supports the hypothesis of an inflammatory ‘‘priming’’ of dental afferents, making them more susceptible to the onset of neuropathic pain in case of subsequent trauma. The role of neuroinflammation in chronic pain is a well-documented phenomenon, leading to phenotypical and functional properties of neuronal primary sensory afferents [5,6]. It is therefore tempting to offer such a hypothesis to explain the results of this study. For instance, the chemokine CCL2, one of the key molecular signatures of neuropathic pain could be released by odontoblasts in reaction to a bacterial challenge and activate glial cells in the trigeminal ganglia and trigeminal sensory complex [2]. Other inflammatory molecules such as chemokines, cytokines, matrix metalloproteinases (MMP) or matrikines can drive similar neural sensitization mediated – for the most part – by glial cells. For example, the stimulation of innate immunity Toll-Like Receptors (TLRs) by Pathogen-Associated Molecular Patterns (PAMPs) and DamageAssociated Molecular Patterns (DAMPs) results in neuronal, glial and vascular activation and neuroinflammation [9,10]. More specifically, lipopolysaccharide (LPS) has been shown to sensitize TRPV1 trigeminal neurons in the dental pulp via the activation of TLR4 [11,12]. It is also interesting to note that inflammation of the dental pulp leads to changes in neuronal phenotypes. For example, NaV1.8 channels (TTX-insensitive) are overexpressed in chronic inflammation of the pulp, these channels being selectively involved in neuropathic pain development [13]. Taken together, these data suggest that bacterial inflammation can induce neuronal phenotypic changes responsible for an increased risk of neuropathic pain development following a subsequent iatrogenic lesion. It is also of interest to note the gender differences in TLR4 receptors regarding neuropathic pain. For instance, mechanical allodynia developing after neuropathic injury was partially reversed in male mice but not in females after pharmacological blockade of TLR4 [14] underlining the modulation of TLR4 by sex hormones, possibly via estradiol metabolites. Another explanation for our results could be that the pain prior to the dental deafferentation was not of inflammatory origin. The pain could already be of neuropathic origin although not traumatic, for instance resulting from an undiagnosed viral infection, metabolic condition, hormonal imbalance or impairment of descending controls etc. as suggested by Woda [15]. Therefore, dental deafferentation would not be necessary to induce neuropathic pain. The preexisting neuropathic pain would have been misdiagnosed and would have led to a logical failure of dental treatments to relieve the pain. In this regard, Pak and White [16] reported that 4% of ET performed in their study did not improve the dental pain, suggesting a misdiagnosis. Also, a recent study found that among patients still suffering six months after ET, 42% of them had non-odontogenic pain (mainly temporo-mandibular disorders) and only 37% had odontogenic pain (from the treated tooth or from an adjacent tooth) [17]. The fact that dental care was performed in 39 patients (70%) in the present study nevertheless supports the idea that these pains had characteristics of inflammatory pain, although neuropathic
W. Dieb et al. / J Stomatol Oral Maxillofac Surg 118 (2017) 147–150
150
pain being a not well-known entity among general dental practitioners could have easily been overlooked.
[2]
5. Limitations of the study Several limitations may weaken the conclusions which may be drawn from this study. First of all, the retrospective design of the study made it impossible to collect all the desired information. For example, in 13 of the 56 cases of orofacial neuropathic pain, it was not possible to determine whether the neuropathic pain was preceded by a painful episode or not. The second limitation of this study is the imprecision in recalling the characteristics of prior painful episodes, rendering it difficult to distinguish between neuropathic and inflammatory pain. Indeed, as chronic pain has become such an important part of the patients’ daily lives, it is often difficult for them to remember the initial pain characteristics comparatively to the current ones. Authors’ contribution Y.B. and W.D. designed the research; I.C. collected and analyzed the data. N.M., W.D. and Y.B. analyzed the data. Y.B. and N.M. drafted the manuscript. All authors commented on the manuscript and approved the final version. Disclosure of interest The authors declare that they have no competing interest.
[3]
[4] [5] [6] [7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
Acknowledgements [15]
This work was funded by UFR Odontologie, University Paris Diderot. References [1] Latre´molie`re A, Mauborgne A, Masson J, Bourgoin S, Kayser V, Hamon M, et al. Differential implication of proinflammatory cytokine interleukin-6 in the
[16] [17]
development of cephalic versus extracephalic neuropathic pain in rats. J Neurosci 2008;28:8489–501. Dauvergne C, Molet J, Reaux-Le Goazigo A, Mauborgne A, Me´lik-Parsadaniantz S, Boucher Y, et al. Implication of the chemokine CCL2 in trigeminal nociception and traumatic neuropathic orofacial pain. Eur J Pain 2013;18: 368–75. Haviv Y, Zadik Y, Sharav Y, Benoliel R. Painful traumatic trigeminal neuropathy: an open study on the pharmacotherapeutic response to stepped treatment. J Oral Fac Pain Headache 2014;28:52–60. Benoliel R, Kahn J, Eliav E. Peripheral painful traumatic trigeminal neuropathies. Oral Dis 2012;18:317–32. Ren K, Dubner R. Interactions between the immune and nervous systems in pain. Nat Med 2010;16:1267–76. Ji R-R, Xu Z-Z, Gao Y-J. Emerging targets in neuroinflammation-driven chronic pain. Nat Rev Drug Discov 2014;13:533–48. Benoliel R, Zadik Y, Eliav E, Sharav Y. Peripheral painful traumatic trigeminal neuropathy: clinical features in 91 cases and proposal of novel diagnostic criteria. J Orofac Pain 2012;26:49–58. Oshima K, Ishii T, Ogura Y, Aoyama Y, Katsuumi I. Clinical investigation of patients who develop neuropathic tooth pain after endodontic procedures. J Endod 2009;35:958–61. Tanga FY, Nutile-McMenemy N, DeLeo JA. The CNS role of Toll-like receptor 4 in innate neuroimmunity and painful neuropathy. Proc Natl Acad Sci USA 2005;102:5856–61. Henn A, Kirner S, Leist M. TLR2 hypersensitivity of astrocytes as functional consequence of previous inflammatory episodes. J Immunol 2011;186: 3237–47. Ferraz CCR, Henry MA, Hargreaves KM, Diogenes A. Lipopolysaccharide from Porphyromonas gingivalis sensitizes capsaicin-sensitive nociceptors. J Endod 2011;37:45–8. Diogenes A, Ferraz CCR, Akopian AN, Henry MA, Hargreaves KM. LPS sensitizes TRPV1 via activation of TLR4 in trigeminal sensory neurons. J Dent Res 2011;90:759–64. Renton T, Yiangou Y, Plumpton C, Tate S, Bountra C, Anand P. Sodium channel Nav1.8 immunoreactivity in painful human dental pulp. BMC Oral Health 2005;5:5. Sorge RE, LaCroix-Fralish ML, Tuttle AH, Sotocinal SG, Austin J-S, Ritchie J, et al. Spinal cord Toll-like receptor 4 mediates inflammatory and neuropathic hypersensitivity in male but not female mice. J Neurosci 2011;31:15450–4. Woda A. A ‘‘dysfunctional’’ pain group in addition to the ‘‘neuropathic’’ and ‘‘nociception/inflammatory’’ groups of orofacial pain entities? J Orofac Pain 2009;23:89–90. Pak JG, White SN. Pain prevalence and severity before, during, and after root canal treatment: a systematic review. J Endod 2011;37:429–38. Nixdorf DR, Law AS, John MT, Sobieh RM, Kohli R, Nguyen RHN, et al. Differential diagnoses for persistent pain after root canal treatment: a study in the National Dental Practice-based Research Network. J Endod 2015;41: 457–63.
Available online at
ScienceDirect www.sciencedirect.com
Original Article
Neuropathic pain in the orofacial region: The role of pain history. A retrospective study W. Dieb a, N. Moreau b, I. Chemla a, V. Descroix a, Y. Boucher a,* a b
UFR d’Odontologie, Universite´ Paris Diderot, Hoˆpital Pitie´ Salpeˆtrie`re, Paris, France UFR d’Odontologie, Universite´ Paris Descartes, Hoˆpital Bretonneau, Paris, France
A R T I C L E I N F O
A B S T R A C T
Article history: Received 6 September 2016 Accepted 16 March 2017 Available online 29 March 2017
Introduction: Orofacial neuropathic pain is often difficult to treat, mostly because of still unclear underlying mechanisms. The occurrence of such neuropathic pain varies depending on different factors, of which preexisting preoperative pain seems to be of high importance. The aim of this study was thus to test the hypothesis that prior history of pain could indeed be considered a risk factor for the development of orofacial neuropathic pain in the same region. Methods: The study was performed in the dental department of the Groupe Hospitalier Pitie´-Salpeˆtrie`re (GHPS) in Paris, France. We investigated the presence of prior inflammatory pain before development of orofacial neuropathic pain in 56 patients. For each patient file, the following items were collected: age, gender; medical history; diagnosis; description of the pain (at time of consultation); presence or absence of prior dental treatment; date and type of dental treatment received. Results: 41 patients (73%) of orofacial neuropathic pain patients had a history of pain compatible with an inflammatory condition; 4% (n = 2) did not report any prior pain and 23% (n = 13) could not remember. Among the patients with documented history of pain prior to neuropathy, 88% (n = 36) received surgical treatment; 61%, (n = 25) endodontic treatment and 22%, (n = 9) restorative treatment. All eventually received endodontic treatment or tooth extraction. These dental treatments are compatible with the hypothesis of prior inflammatory pain in these patients. Conclusion: These results support the hypothesis that prior inflammatory pain could favor the development of orofacial neuropathic pain. Prevention and treatment of inflammatory trigeminal pain may therefore play a key role in preventing future neuropathic pain development.
C 2017 Elsevier Masson SAS. All rights reserved.
Keywords: Trigeminal Neuropathic pain Priming Inflammation Endodontics
1. Introduction Post-traumatic neuropathic pain is a chronic condition difficult to endure and to treat, especially trigeminal neuropathic pain which is specific in its pathophysiology [1,2] and available treatments [3] as compared to its spinal counterpart. The prevalence of this painful condition ranges from 0.5% to 12% following oral surgery, including orthograde endodontic treatments (ET) as well as retrograde surgical endodontic treatments, dental extractions, cystic enucleations, orthognathic surgery or dental implants and may vary according to different factors, among which age, gender, importance of nerve damage, type of surgery, surgical technique and the presence of preoperative pain [4]. Regarding the latter, most common dental pains (resulting from caries and periodontal diseases) are caused by microorganisms
* Corresponding author at: UFR d’Odontologie, 5, rue Garancie`re, 75006 Paris, France. E-mail address: [email protected] (Y. Boucher). http://dx.doi.org/10.1016/j.jormas.2017.03.004 C 2017 Elsevier Masson SAS. All rights reserved. 2468-7855/
triggering inflammatory reactions and exposing primary afferent neurons to algogenic substances. Some of these molecules are known to drive phenotypic and functional changes in nerve and surrounding glial, immune and vascular cells [5,6]. It can therefore be hypothesized that nerve trauma occurring in an inflammatory environment might favor the onset of neuropathic pain. The aim of this study was to test this hypothesis from a clinical standpoint. In a retrospective analysis of a sample of patients diagnosed with orofacial neuropathic pain, we investigated the evidence in favor of a history of pain resulting from local inflammatory conditions prior to surgical trauma. 2. Methods and patients 2.1. Sample The study was performed in the dental department of the Groupe Hospitalier Pitie´-Salpeˆtrie`re (GHPS) in Paris, France. Medical files of patients who attended the chronic orofacial pain
148
W. Dieb et al. / J Stomatol Oral Maxillofac Surg 118 (2017) 147–150
consultation, within a secondary/tertiary referral center, between 09/03/2012 and 12/19/2014 were retrieved from the hospital database and analyzed. The study was approved by the board of the dental department. Authorization for retrieval and use of patient data was obtained from the Commission Nationale de l’Informatique et des Liberte´s (CNIL) (#1839648). 2.2. Consultation and diagnosis All consultations were performed by the same trained experienced senior practitioner (YB) according to a previously described methodology [7]. This standard examination included (1) detailed medical history including medications, pain comorbidities, history of spinal/cranial traumatic events, psychological status, gross cranial nerve functional assessment; (2) specific pain history and characteristics including time course, quality, associate autonomic signs, interference with sleep; (3) extraoral clinical evaluation including TMJ, masticatory and neck muscles assessment; (4) intraoral examination including mechanical/thermal/ electrical tooth sensitivity tests, oral mucosa and soft tissues examination including testing for hypoesthesia/hyperesthesia with the use of a sharp and blunt stimulus, static and mechanical allodynia using digital pressure rubbing of the painful areas, compared with the contralateral sites and (5) relevant dental and/ or facial imagery. Quality of endodontic treatments was evaluated radiographically using standard X-rays or cone beam computed tomography CBCT in doubtful cases. Patients were referred to other medical specialists (neurologist, ENT specialist, etc.) when needed. 2.3. Exclusion and inclusion criteria Patients diagnosed with definitive orofacial neuropathic pain, according to the criteria of Benoliel et al. [4], were included in the study, i.e. satisfying criteria A B C D and E: (A) spontaneous or touchevoked (stimulus dependent) pain predominantly affecting the receptive field of one or more divisions of the trigeminal nerve. Duration ranges widely from episodic (minutes to days) and may also be constant; (B) develops within 3 months of an identifiable traumatic event to the painful area or relevant innervation; continues for more than 3 months; (C) at least one clinically evident neurological dysfunction: positive sign (hyperalgesia/allodynia/ swelling or flushing) and/or: negative sign anesthesia/hypoesthesia; (D) imaging or neurophysiology demonstrating a neurological lesion and its location. Endodontic treatments or avulsions were taken as evidence as nerve lesion – no neurophysiologic evaluation, like Quantitative Sensory Testing (QST) or evoked potentials, was performed in this study; (E) not attributed to another disorder. For each neuropathic pain patient file, the following items were collected: age, gender; medical history; diagnosis; description of the pain including location, presence of DN4 neuropathic pain questionnaire items, i.e. burning/tingling/numbness/electrical shocks/allodynia; increase or not during the day; Visual Analog Scale (VAS) score; history of pain (presence/absence and date of prior dental treatments); date and type of dental treatment (restorative, endodontic or surgical). Data was transcripted on an Excel spreadsheet (MicrosoftTM) and anonymized before analysis.
Fig. 1. Distribution of the sample according to age. Total range was 31–89.
54.0 14.4 years old. Only 13% of patients did not present any significant health issue. The majority had one or more comorbidities which were mostly: osteoarthritis (21%; n = 12), headache (18%; n = 10), hypertension (18%; n = 10) or history of trauma (whiplash, falls, blows, etc.) (11%; n = 6). 82% of patients (n = 46) had at least one chronic condition (hepatitis, diabetes, high cholesterol, etc.) prior to consultation. In addition, 27% of patients (n = 15) reported chronic stress (resulting from severe family or professional issues, etc.) and 23% (n = 13) had documented psychological/psychiatric background (depression, schizophrenia, etc.); 37.5% of patients (n = 21) combined both chronic stress and psychological/psychiatric ailments. Characteristics of the pain: Pain location from the different cases is summarized in Fig. 2. In some cases, simultaneous pain in multiple locations was described. Most commonly cited descriptors of the pain (Fig. 3) adhered with classical neuropathic pain descriptors although 88% of patients (n = 49) expressed atypical complaints (swelling sensation, tingling, etc.). Mechanical allodynia was present in 34% of cases (n = 19). History of prior pain: About two-thirds of patients from the sample (73%; n = 41), reported prior episodes of pain before being diagnosed with orofacial neuropathic pain, 4% (n = 2) did not report any prior pain and 23% (n = 13) could not remember (Fig. 4). Among these 41 patients who were identified as having a painful history prior to neuropathy, dental treatments received prior to the onset of neuropathic pain were, in order of decreasing frequency:
3. Results 268 records of patients attending the pain consultation were identified in the database. Among them, 229 could be retrieved and 56 cases were classified as orofacial neuropathic pain. This group constituted the sample, which comprised 6 men (11%) and 50 women (89%; 55% of which were menopaused). Age of patients ranged from 32 to 89 years (Fig. 1) with a mean age of
Fig. 2. Main localization of pain symptoms. One patient could also experience several localizations.
W. Dieb et al. / J Stomatol Oral Maxillofac Surg 118 (2017) 147–150
149
4. Discussion
Fig. 3. Main characteristics of the pain reported by the patient or assessed by the examiner.
Fig. 4. Distribution of patients according to the history of pain prior to the diagnosis of orofacial neuropathic pain (ET = endodontic treatment). See text for details.
(1) surgical treatments (88%; n = 36) which consisted of extractions, cystic enucleation or endodontic surgery; (2) endodontic treatments (ET) (61%; n = 25); (3) restorative treatments (22%; n = 9). All patients with restorative treatments eventually received endodontic treatment or tooth extraction. Only 2 patients (4%) from this group did not receive any of these three types of treatments. One of the two patients claimed that his (neuropathic) pain appeared after painful gingival inflammation caused by an overextended crown margin; the second remembered having a different type of pain prior to the most recent painful episodes that motivated his last consultation, without being able to remember the cause of such previous pain.
The general characteristics of this sample are in accordance with those from other studies of neuropathic facial pains, i.e. mostly menopausal women with psychological distress and frequent comorbidities. No preferential localization was found in our sample which is not in accordance with another study [8] reporting neuropathic pain preferentially located on the maxillae. The main result of this study is that almost 3/4 of the patients (73%) with a diagnosis of orofacial neuropathic pain reported pain in a tooth or gingiva prior to the dental treatment-related nerve lesion and almost all of these (95%; 39 out of 41) received prior dental treatment compatible with a diagnosis of an inflammatory disease. This supports the hypothesis of an inflammatory ‘‘priming’’ of dental afferents, making them more susceptible to the onset of neuropathic pain in case of subsequent trauma. The role of neuroinflammation in chronic pain is a well-documented phenomenon, leading to phenotypical and functional properties of neuronal primary sensory afferents [5,6]. It is therefore tempting to offer such a hypothesis to explain the results of this study. For instance, the chemokine CCL2, one of the key molecular signatures of neuropathic pain could be released by odontoblasts in reaction to a bacterial challenge and activate glial cells in the trigeminal ganglia and trigeminal sensory complex [2]. Other inflammatory molecules such as chemokines, cytokines, matrix metalloproteinases (MMP) or matrikines can drive similar neural sensitization mediated – for the most part – by glial cells. For example, the stimulation of innate immunity Toll-Like Receptors (TLRs) by Pathogen-Associated Molecular Patterns (PAMPs) and DamageAssociated Molecular Patterns (DAMPs) results in neuronal, glial and vascular activation and neuroinflammation [9,10]. More specifically, lipopolysaccharide (LPS) has been shown to sensitize TRPV1 trigeminal neurons in the dental pulp via the activation of TLR4 [11,12]. It is also interesting to note that inflammation of the dental pulp leads to changes in neuronal phenotypes. For example, NaV1.8 channels (TTX-insensitive) are overexpressed in chronic inflammation of the pulp, these channels being selectively involved in neuropathic pain development [13]. Taken together, these data suggest that bacterial inflammation can induce neuronal phenotypic changes responsible for an increased risk of neuropathic pain development following a subsequent iatrogenic lesion. It is also of interest to note the gender differences in TLR4 receptors regarding neuropathic pain. For instance, mechanical allodynia developing after neuropathic injury was partially reversed in male mice but not in females after pharmacological blockade of TLR4 [14] underlining the modulation of TLR4 by sex hormones, possibly via estradiol metabolites. Another explanation for our results could be that the pain prior to the dental deafferentation was not of inflammatory origin. The pain could already be of neuropathic origin although not traumatic, for instance resulting from an undiagnosed viral infection, metabolic condition, hormonal imbalance or impairment of descending controls etc. as suggested by Woda [15]. Therefore, dental deafferentation would not be necessary to induce neuropathic pain. The preexisting neuropathic pain would have been misdiagnosed and would have led to a logical failure of dental treatments to relieve the pain. In this regard, Pak and White [16] reported that 4% of ET performed in their study did not improve the dental pain, suggesting a misdiagnosis. Also, a recent study found that among patients still suffering six months after ET, 42% of them had non-odontogenic pain (mainly temporo-mandibular disorders) and only 37% had odontogenic pain (from the treated tooth or from an adjacent tooth) [17]. The fact that dental care was performed in 39 patients (70%) in the present study nevertheless supports the idea that these pains had characteristics of inflammatory pain, although neuropathic
W. Dieb et al. / J Stomatol Oral Maxillofac Surg 118 (2017) 147–150
150
pain being a not well-known entity among general dental practitioners could have easily been overlooked.
[2]
5. Limitations of the study Several limitations may weaken the conclusions which may be drawn from this study. First of all, the retrospective design of the study made it impossible to collect all the desired information. For example, in 13 of the 56 cases of orofacial neuropathic pain, it was not possible to determine whether the neuropathic pain was preceded by a painful episode or not. The second limitation of this study is the imprecision in recalling the characteristics of prior painful episodes, rendering it difficult to distinguish between neuropathic and inflammatory pain. Indeed, as chronic pain has become such an important part of the patients’ daily lives, it is often difficult for them to remember the initial pain characteristics comparatively to the current ones. Authors’ contribution Y.B. and W.D. designed the research; I.C. collected and analyzed the data. N.M., W.D. and Y.B. analyzed the data. Y.B. and N.M. drafted the manuscript. All authors commented on the manuscript and approved the final version. Disclosure of interest The authors declare that they have no competing interest.
[3]
[4] [5] [6] [7]
[8]
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