Chronic Orofacial Pain Research Articles

Letter to the Editor: Venous Neurovascular Compression and Chronic Orofacial Pain

Letter to the Editor: Venous Neurovascular Compression and Chronic Orofacial Pain

Orofacial pain for clinicians: A review of constant and attack-like facial pain syndromes.

Primary headache syndromes such as migraine are among the most common neurological syndromes. Chronic facial pain syndromes of non-odontogenic cause are less well known to neurologists despite being highly disabling. Given the pain localization, these patients often consult dentists first who may conduct unnecessary dental interventions even if a dental cause is not identified. Once it becomes clear that dental modalities have no effect on the pain, patients may be referred to another dentist or orofacial pain specialist, and later to a neurologist. Unfortunately, neurologists are also often not familiar with chronic orofacial pain syndromes although they share the neural system, i.e., trigeminal nerve and central processing areas for headache disorders. In essence, three broad groups of orofacial pain patients are important for clinicians: (i) Attack-like orofacial pain conditions, which encompass neuralgias of the cranial nerves and less well-known facial variants of primary headache syndromes; (ii) persistent orofacial pain disorders, including neuropathic pain and persistent idiopathic facial/dentoalveolar pain; and (iii) other differential diagnostically relevant orofacial pain conditions encountered by clinicians such as painful temporomandibular disorders, bruxism, sinus pain, dental pain, and others which may interfere (trigger) and overlap with headache. It is rewarding to know and recognize the clinical picture of these facial pain syndromes, given that, just like for headache, an internationally accepted classification system has been published and many of these syndromes can be treated with medications generally used by neurologists for other pain syndromes.

Sialadenitis of the anterior mandibular vestibule: A subset of burning mouth syndrome

Burning Mouth syndrome (BMS) is a relatively common oral neurosensory disorder known for oral burning pain. In that there is a relative absence of oral clinical findings and systemic causation, the diagnosis of BMS is challenging. Sialadenitis of the anterior mandibular vestibule appears to be a subset of BMS. The lip component of chronic orofacial pain is potentially an important concern with regard to the diagnosis and treatment of chronic orofacial pain. Discussion regarding the etiology, diagnosis, and therapy of this condition is provided.

Evaluation of anxiety disorder in patients with trigeminal neuralgia.

The aim of this cross-sectional study was to evaluate the relationship between anxiety levels and severity of trigeminal neuralgia (TN) disorder's chronic orofacial pain during 2019-2020 in Shiraz Dental Faculty. In this study, patients with TN disorder who were referred to the Oral Medicine Department of Shiraz Dental Faculty were evaluated. Individuals were selected based on convenience sampling. Finally, 47 patients with TN were recruited in this study. Satisfaction with treatment was recorded based on controlling the patient's pain, age, sex, and frequency of recurrence, and data were analyzed using SPSS18. The Chi-square test was used to compare the final results. A reliability of more than 95% was considered significant (P < 0.05). According to the results, the mean ages of participants with TN and control groups were 56.89 ± 10.93 and 37.12 ± 9.55, respectively. The mean value of participants' age was significantly different between the two evaluated groups (P < 0.0001). The anxiety of patients with TN was significantly higher than the healthy control group (P < 0.0001). The mean level of anxiety in patients with TN and also in healthy controls was not significantly different among men and women (P > 0.05). The mean level of anxiety of men and women in TN group was significantly higher than the healthy control women (P = 0.001). The mean levels of anxiety between different age ranges in patients with TN and healthy controls were not different in both evaluated groups (P > 0.05). Patients with TN in different age ranges had higher level of anxiety than healthy controls (P < 0.05). Patients with TN had significantly higher level of anxiety than healthy participants.

Burning mouth syndrome- An overview

A burning sensation of the oral mucosa without any obvious oral lesions is a defining feature of the burning mouth syndrome (BMS), a chronic and untreatable orofacial pain syndrome. Women in their later years of life who are experiencing hormonal shifts or psychological issues are most affected by this ailment. BMS patients also complains of pain in oral mucosa, taste perception changes and dry mouth with burning sensation. Even though the exact cause of BMS is unknown, a complicated correlation between biological and psychological components has been found, pointing to the possibility of a multiple etiology. This article's goal is to review the etiology, clinical manifestation, and management of BMS.

Exploring the Effect of Ethnicity on Chronic Orofacial Pain: A Comparative Study of Jewish and Arab Israeli Patients.

The relationship between ethnicity and chronic pain has been studied worldwide. The population of Israel includes two main ethnic groups, 75% Jews and 21% Arabs. The purpose of this study was to compare orofacial chronic pain characteristics and treatment outcomes between Jewish and Arab Israeli citizens. Two hundred patients admitted to the Orofacial Pain Clinic at Hebrew University-Hadassah School of Dental Medicine between 2017 and 2022 were selected randomly for this historical cohort study. Our cohort included 159 (79.5%) Jews and 41 (20.5%) Arabs. Twenty-six pain-related variables were compared of which only two differed significantly between the two groups, awakening due to pain and mean muscle sensitivity; both indicators were higher in the Arab group (p < 0.05). No differences were found in any of the other variables such as diagnosis, pain severity, onset, and treatment outcome. This minimal difference may be explained by the equal accessibility to medical services for all citizens, and the diversity of our staff that includes Jew as well as Arab service providers. These factors minimize or even eliminate racial bias, language, and cultural barriers, and is reflected in the minor differences in orofacial pain characteristics found between the two main ethnic groups in Israel.

Pathophysiology, Clinical Implications and Management of Orofacial Neuropathic Pain- with special attention to Trigeminal neuralgia: A Narrative Review

Background: It is a widely held belief that if the trigeminal nerve is damaged, the victim would experience agonising and unrelenting external pain. A lesion to the trigeminal nerve may have a wide-reaching effect, such as on one side of the face in particular, or it might have a more localised effect, such as on some or all of your gums. The risk of damage increases the likelihood that it will be difficult to speak and swallow. This nerve provides sensation to a part of your face that may be constantly aching or tingling for some people. However, the trigeminal nerve injury-related persistent orofacial pain might be brought on by a wide variety of unknown triggers. Aim: In this study investigate the clinical manifestations of chronic orofacial pain brought on by a damage to the trigeminal nerve, as well as the diagnostic and therapeutic approaches available to treat this condition. Methodology Through the use of search phrases such as "Trigeminal nerve injury," "Trigeminal ganglion," "Trigeminal spinal subnucleus caudalis," "Craniofacial pain," "Oral prognosis," and "treatment," the computerised databases for the last twenty years have been investigated. There are now two hundred objects in total that have been accumulated. There have been around fifty of them that are pertinent to the discussion that is going on in this work. Majority of the patients fair enough with the pharmacology treatment/drugs like the carbamazepine &amp; oxcarbazepine which forms the first line treatment options followed by lamotrigine &amp; baclofen encompassing the second line of drugs along with adjuvant drug support of topiramate, levetiracetam, gabapentin, pregabalin. As the field of science has explored &amp;advanced for the latest treatment options include microvascular decompression, gamma knife radiosurgery, percutaneous rhizotomies variable based on the evidences &amp; guidelines 54 Conclusion: New diagnostic criteria and treatment alternatives have become available for people who suffer from trigeminal neuropathy and orofacial neuropathic pain as a result of recent developments in fundamental animal research that have led to their development. Despite the results, more research needs to investigate a greater variety of distinct non-neuronal cell feature approaches.

Remodeling dental anatomy vs sham therapy for chronic temporomandibular disorders. A placebo-controlled randomized clinical trial

BackgroundEvidence regarding the etiology or effective treatments for chronic orofacial pain, the majority diagnosed as temporomandibular disorder (TMD), is limited. PurposeTo investigate whether occlusal equilibration therapy (ET) and decreasing the (higher) angle of the lateral guidance on the nonworking-side leads to a reduction in chronic TMDs intensity. MethodsIt was conducted a randomized, explanatory, single blind with blinded assessment, placebo-controlled trial with strong protection against bias involving patients with chronic TMDs. Participants were randomly assigned to receive equilibration therapy or sham therapy. ET in this study consisted of minimal invasive occlusal remodeling to obtain balanced occlusion with reduction of the steeper angle of lateral mandibular movement with respect to the Frankfort plane. The primary outcome was a change in the pain intensity score (on a 0–10 point scale, with 0 indicating no pain and 10 the worst possible pain) at month 6. Secondary outcomes include maximum unassisted mouth opening and psychological distress. ResultsA total of 77 participants underwent randomization, 39 of whom received ET and 38 sham therapy. The trial was stopped early for efficacy, according to preestablished rules when 67 participants (n = 34, n = 33, respectively) had completed the analysis. At month 6, the mean unadjusted pain intensity score was 2.1 in the ET and 3.6 in the sham therapy group (adjusted mean difference, −1.54; 95% confidence interval [CI] −0.5 to −2.6; P = 0.004; ANCOVA model). The mean increase in maximum unassisted mouth opening (main secondary outcome) was significantly higher in the real therapy group (adjusted mean difference 3.1 mm, 95% CI 0.5–5.7, p = 0.02). ConclusionET significantly reduced the intensity of facial pain associated with chronic TMDs and increased maximum unassisted mouth opening, as compared with sham therapy, over the course of 6 months. There were no serious adverse events.Funded by the Instituto de Salud Carlos III from the Ministry of Science and Innovation of the Government of Spain and European Regional Development Fund, Grant nº PI11/02507; “una manera de hacer Europa”.

The role of cannabidiol in modulating chronic neuropathic orofacial pain

Chronic neuropathic orofacial pain is an extremely debilitating disorder that poses a burden to patients as well as the economy. Although a common condition, the management and treatment for those affected remains limited. Cannabidiol is a safe, non-psychoactive compound derived from the Cannabis sativa plant, which possesses properties that can modulate pain, including anti-neuropathic, anti-nociception and anti-inflammatory capacities. Although research is limited, cannabidiol may be able to treat chronic orofacial pain in some neurological, neurovascular and idiopathic conditions. This article aims to increase awareness of cannabidiol, and its possible use for future treatment of chronic neuropathic orofacial pain. CPD/Clinical Relevance: Cannabidiol may be useful as a treatment for chronic neuropathic orofacial pain.

Association between Oxidative Stress and Chronic Orofacial Pain and Potential Druggable Targets: Evidence from a Mendelian Randomization Study

Association between Oxidative Stress and Chronic Orofacial Pain and Potential Druggable Targets: Evidence from a Mendelian Randomization Study

Preclinical orofacial pain assays and measures and chronic primary orofacial pain research: where we are and where we need to go.

Chronic primary orofacial pain (OFP) conditions such as painful temporomandibular disorders (pTMDs; i.e., myofascial pain and arthralgia), idiopathic trigeminal neuralgia (TN), and burning mouth syndrome (BMS) are seemingly idiopathic, but evidence support complex and multifactorial etiology and pathophysiology. Important fragments of this complex array of factors have been identified over the years largely with the help of preclinical studies. However, findings have yet to translate into better pain care for chronic OFP patients. The need to develop preclinical assays that better simulate the etiology, pathophysiology, and clinical symptoms of OFP patients and to assess OFP measures consistent with their clinical symptoms is a challenge that needs to be overcome to support this translation process. In this review, we describe rodent assays and OFP pain measures that can be used in support of chronic primary OFP research, in specific pTMDs, TN, and BMS. We discuss their suitability and limitations considering the current knowledge of the etiology and pathophysiology of these conditions and suggest possible future directions. Our goal is to foster the development of innovative animal models with greater translatability and potential to lead to better care for patients living with chronic primary OFP.

Descending serotonergic modulation from rostral ventromedial medulla to spinal trigeminal nucleus is involved in experimental occlusal interference-induced chronic orofacial hyperalgesia

BackgroundDental treatment associated with unadaptable occlusal alteration can cause chronic primary myofascial orofacial pain. The serotonin (5-HT) pathway from the rostral ventromedial medulla (RVM) exerts descending modulation on nociceptive transmission in the spinal trigeminal nucleus (Sp5) and facilitates chronic pain. The aim of this study was to investigate whether descending 5-HT modulation from the RVM to the Sp5 is involved in the maintenance of primary myofascial orofacial hyperalgesia after persistent experimental occlusal interference (PEOI) or after delayed removal of experimental occlusal interference (REOI).MethodsExpressions of 5-HT3A and 5-HT3B receptor subtypes in the Sp5 were assessed by immunofluorescence staining and Western blotting. The release and metabolism of 5-HT in the Sp5 were measured by high-performance liquid chromatography. Changes in the pain behavior of these rats were examined after specific pharmacologic antagonism of the 5-HT3 receptor, chemogenetic manipulation of the RVM 5-HT neurons, or selective down-regulation of 5-HT synthesis in the RVM.ResultsUpregulation of the 5-HT3B receptor subtype in the Sp5 was found in REOI and PEOI rats. The concentration of 5-HT in Sp5 increased significantly only in REOI rats. Intrathecal administration of Y-25130 (a selective 5-HT3 receptor antagonist) dose-dependently reversed the hyperalgesia in REOI rats but only transiently reversed the hyperalgesia in PEOI rats. Chemogenetic inhibition of the RVM 5-HT neurons reversed the hyperalgesia in REOI rats; selective down-regulation of 5-HT in advance also prevented the development of hyperalgesia in REOI rats; the above two manipulations did not affect the hyperalgesia in PEOI rats. However, chemogenetic activation of the RVM 5-HT neurons exacerbated the hyperalgesia both in REOI and PEOI rats.ConclusionsThese results provide several lines of evidence that the descending pathway from 5-HT neurons in the RVM to 5-HT3 receptors in the Sp5, plays an important role in facilitating the maintained orofacial hyperalgesia after delayed EOI removal, but has a limited role in that after persistent EOI.Graphical

Individual Dimensions of Pain Catastrophizing Do Not Mediate the Effect of Sociodemographic and Psychological Factors on Chronic Orofacial Pain Severity, Interference, and Jaw Limitation: A Structural Equation Modeling Approach

Pain catastrophization (PC), involving rumination, magnification, and helplessness, can be viewed as a coping strategy associated with chronic pain. PC is considered a driving force in mediating pain-related outcomes, but it is still unclear whether PC mediates the relationship between psychological and sociodemographic factors with chronic pain when considered in a single model. Using baseline data from a parent study, this study examined the effect of positive and negative psychological and sociodemographic factors on pain severity, interference, and jaw limitation mediated by the PC dimensions in a sample of 397 temporomandibular disorder (TMD) participants using structural equation modeling (SEM). SEM revealed that pain severity regressed on age, sex, education, and income; interference regressed on positive and negative psychological factors, education, and income; and jaw limitation regressed on age. The PC dimensions did not individually mediate these relationships. Although they jointly mediated the relationships between negative psychological factors and pain severity and between age and pain interference, the effect size was small, suggesting that PC is not a critical factor in mediating TMD pain outcomes. Reducing negative cognitions, not just PC, may be of greatest benefit to the most vulnerable TMD populations. PerspectiveThis study examines sociodemographic and psychological factors that affect orofacial pain, finding that the pain catastrophizing dimensions do not mediate these relationships. Understanding which factors most strongly affect pain outcomes will help identify targets for intervention to produce the greatest benefit for the most vulnerable persons suffering from pain.

Centers for Disease Control and Prevention Clinical Practice Guideline for Prescribing Opioids: United States, 2022: What dentists need to know

BackgroundThe Centers for Disease Control and Prevention (CDC) published the Clinical Practice Guideline for Prescribing Opioids for Pain—United States, 2022 (CDCCPG) to replace the 2016 guideline. This guideline was designed to serve as a clinical tool to improve communication between clinicians and patients and empower them to make informed, person-centered decisions regarding pain management and the prescribing of opioids. It is intended for primary care and other clinicians, including dentists, who provide pain management for adults with acute, subacute, and chronic pain. Types of Studies ReviewedThis article summarizes the CDCCPG, with an emphasis on information of relevance to dentistry. ResultsFor dentists, the most important recommendations for pain management are that nonsteroidal anti-inflammatory medications are first-line medications for acute dental pain, interdisciplinary care for chronic orofacial pain is indicated, and opioids should only be prescribed for acute dental pain for a maximum of 3 days after risk assessment. Practical ImplicationsThe CDCCPG contains a great deal of relevant information that can help dentists and dental specialists make safe, effective, and evidence-based decisions in providing pain control for their patients.

The mTOR inhibitor rapamycin suppresses trigeminal neuropathic pain and p-MKK4/p-p38 mitogen-activated protein kinase-mediated microglial activation in the trigeminal nucleus caudalis of mice with infraorbital nerve injury.

Neuropathic pain caused by trigeminal nerve injury is a typical refractory orofacial chronic pain accompanied by the development of hyperalgesia and allodynia. We previously demonstrated that the mammalian target of rapamycin (mTOR) inhibitor rapamycin suppressed orofacial formalin injection-induced nociception; however, the underlying mechanism is unclear, and it is unknown whether it can reduce trigeminal neuropathic pain. In mice, left infraorbital nerve and partial nerve ligation (ION-pNL) was performed using a silk suture (8-0). Fourteen days after surgery, neuropathic pain behavior was examined on a whisker pad and rapamycin (0.1, 0.3, and 1.0 mg/kg) was administered intraperitoneally. Mechanical and cold sensitivities in the orofacial region were quantified using von Frey filaments and acetone solution, respectively. Changes in mTOR and related proteins, such as p-MKK3/6, p-MKK4, p-JNK, p-ERK, p-p38 MAPK, GFAP, and Iba-1, in the trigeminal nucleus caudalis (TNC) or the trigeminal ganglia (TG) tissues were examined via western blot analysis or immunohistochemistry. Mice demonstrated significant mechanical and cold allodynia 2 weeks following ION-pNL injury, both of which were significantly reduced 1 h after the administration of high-dose rapamycin (1.0 mg/kg). In the TG tissue, ION-pNL surgery or rapamycin treatment did not change p-mTOR and p-4EBP1, but rapamycin reduced the increase of p-S6 and S6 induced by ION-pNL. In the TNC tissue, neither ION-pNL surgery nor rapamycin treatment altered p-mTOR, p-S6, and p-4EBP1 expressions, whereas rapamycin significantly decreased the ION-pNL-induced increase in Iba-1 expression. In addition, rapamycin suppressed the increase in p-p38 MAPK and p-MKK4 expressions but not p-MKK3/6 expression. Moreover, p-p38 MAPK-positive cells were colocalized with increased Iba-1 in the TNC. Our findings indicate that rapamycin treatment reduces both mechanical and cold orofacial allodynia in mice with trigeminal neuropathic pain, which is closely associated with the modulation of p-MKK4/p-p38 MAPK-mediated microglial activation in the TNC.

Yoga and massage are associated with small experimental placebo effects in chronic orofacial pain.

Complementary and Integrative Health Approaches (CIHA), including but not limited to, natural products and Mind and Body Practices (MBPs), are promising non-pharmacological adjuvants to the arsenal of pain management therapeutics. We aim to establish possible relationships between use of CIHA and the capacity of descending pain modulatory system in the form of occurrence and magnitude of placebo effects in a laboratory setting. This cross-sectional study investigated the relationship between self-reported use of CIHA, pain disability, and experimentally induced placebo hypoalgesia in chronic pain participants suffering from Temporomandibular Disorders (TMD). In the 361 enrolled TMD participants, placebo hypoalgesia was measured using a well-established paradigm with verbal suggestions and conditioning cues paired with distinct heat painful stimulations. Pain disability was measured with the Graded Chronic Pain Scale, and use of CIHA were recorded with a checklist as part of the medical history. Use of physically oriented MBPs (e.g., yoga and massage) was associated with reduced placebo effects (F1,2110.44 = 23.15, p < 0.001, Cohen's d = 0.171). Further, linear regressions indicated that greater number of physically oriented MBPs predicted smaller placebo effects (β = -0.17, p = 0.002), and less likelihood of being a placebo responder (OR = 0.70, p = 0.004). Use of psychologically oriented MBPs and natural product were not associated with placebo effects magnitude and responsiveness. Our findings suggest that use of physically oriented CIHA was associated with experimental placebo effects possibly through an optimized capability to recognize distinct somatosensorial stimulations. Future research is needed to understand the mechanisms underlying placebo-induced pain modulation in CIHA users. Chronic pain participants who use physically oriented mind-body practices, such as yoga and massage, demonstrated attenuated experimentally induced placebo hypoalgesia in comparison with those who do not use them. This finding disentangled the relationship between use of complementary and integrative approaches and placebo effects, providing the potential therapeutic perspective of endogenous pain modulation in chronic pain management.

Cannabis and cannabinoid medications for the treatment of chronic orofacial pain: A scoping review

To collate and summarize existing evidence for the use of cannabis and cannabinoids to treat chronic orofacial pain (COP) by oral and maxillofacial surgeons (OMFS), oral medicine specialists (OMS), and orofacial pain specialists (OPS). We systematically screened for sources including a measure of effect of a cannabinoid compound on pain in COP patients that might be treated by our target specialists. Sources were selected by two authors independently. Sources were summarized by country, publication date, objective(s), COP condition(s) studied, cannabinoid(s) studied, methods, results, limitations, and conclusions. A thematic analysis and word cloud were conducted to elucidate commonalities, emphases, and gaps amongst identified sources. Retrieved from MEDLINE, EMBASE, Web of Science Core Collections, Dentistry and Oral Sciences, DARE, CCRCT, and US National Institute of Health and Controlled Trials Register. Of 705 retrieved titles, 8 met inclusion/exclusion criteria and were included for review. Included sources dealt with COP attributed to: head and neck cancer (3), multiple sclerosis-related trigeminal neuralgia-like symptoms (2), post-herpetic neuralgia (1), temporomandibular dysfunction (1), and primary burning mouth syndrome (1). Cannabinoids studied included: self-administered cannabis (3), topical N-palmitoyle-thanolamine (1), topical cannabis extract (1), cannabis sativa oil (1), nabiximols oromucosal spray (1), and nabilone (1). Most sources concluded their respective cannabinoid treatments to provide some therapeutic benefit for COP (6 of 8) and all concluded their treatments to be safe. Current research is wholistically focused, recording outcome measures for pain, anxiety, depression, quality of life, functional disability. Cannabinoids are most often studied as adjunctive and palliative treatments. Cannabinoids are becoming increasingly accessible and might benefit many COP patients. Patients and clinicians require more and higher quality evidence to make confident and informed decisions regarding treatment of COP with cannabis or cannabinoids. This review summarizes current evidence for patients, clinicians, and future researchers.

Oral Health-Related Quality of Life among Chinese Chronic Orofacial Pain Patients with Psychological Health Problems: A Moderated Mediation Model.

Psychological therapies are important for comprehensive chronic orofacial pain (COFP) treatment. This study is to validate the effects of psychological factors on oral health-related quality of life (OHRQoL) among COFP patients in China. Pain catastrophizing, which is a subjective cognitive emotion used to manage the psychological aspects of pain among COFP patients, was examined in relation to COFP severity and OHRQoL. All 479 participants were recruited in Changsha, Hunan Province, China. Cronbach's alpha coefficients (0.868-0.960), composite reliability scores (0.924-0.969), and average variance extracted from each construct (0.555-0.753) all indicated a good model fit. Pearson's correlation analysis showed that age and education status have a positive correlation with COFP severity, pain catastrophizing, and anxiety. COFP severity was related to anxiety, depression, and COFP-OHRQoL. Pain catastrophizing was related to employment status. Anxiety and depression symptoms indirectly mediated the correlation between COFP severity and COFP-OHRQoL. As a second-stage moderator, pain catastrophizing moderated the mediating effects of anxiety symptoms and depression symptoms. Our findings suggest that anxiety, depression, and pain catastrophizing should be evaluated jointly to improve COFP-OHRQoL among COFP patients. This evidence will help therapists to comprehensively treat patients for the best treatment effect.

Why does patient mental health matter? part 5: chronic orofacial pain as a consequence of psychiatric disorders

This is the final article in a series looking at psychiatric presentations in dentistry. Recently, the oral health of people with severe mental illness (SMI) has gained significant media attention after the Office of the Chief Dental Officer for England published a statement on the importance of prioritizing oral health for people with SMI. Furthermore, a consensus statement has set out a 5-year plan to improve oral health in people with SMI. In Part 4, we discussed how a psychiatric disorder can result in dental pathology by contributing to risk factors associated with tooth surface loss. This article explores chronic orofacial pain symptoms and their link with psychiatry, considering the role of the primary dental care team in early recognition of psychiatric disorders. Given the range of chronic orofacial pain subtypes, we will present two separate fictionalized case-based discussions to explore their presentation. CPD/Clinical Relevance: The primary care dental team has a role in recognition of psychiatric conditions and subsequent chronic orofacial pain.

Editorial: Chronic Orofacial Pain in Older Adults.

No summary.