Acute pulpitis promotes purinergic signaling to induce pain in rats via P38MAPK/NF-κB signaling pathway.

Toothache is one of the most common types of pain, but the mechanisms underlying pulpitis-induced pain remain unknown. The ionotropic purinergic receptor family (P2X) is reported to mediate nociception in the nervous system. This study aims to investigate the involvement of P2X3 in the sensitisation of the trigeminal ganglion (TG) and the inflammation caused by acute pulpitis. An acute tooth inflammation model was established by applying LPS to the pulp of SD rats. We found that the increased expression of P2X3 was induced by acute pulpitis. A selective P2X3 inhibitor (A-317491) reduced pain-like behavior in the maxillofacial region of rats and depressed the activation of neurons in the trigeminal ganglion induced by pulpitis. The upregulated MAPK signaling (p-p38, p-ERK1/2) expression in the ipsilateral TG induced by pulpitis could also be depressed by the application of the P2X3 inhibitor. Furthermore, the expression of markers of inflammatory processes, such as NF-κB, TNF-α and IL-1ß, could be induced by acute pulpitis and deduced by the intraperitoneal injection of P2X3 antagonists. Our findings demonstrate that purinergic P2X3 receptor signaling in TG neurons contributes to pulpitis-induced pain in rats and that P2X3 signaling may be a potential therapeutic target for tooth pain.

Prevalence of Trigeminal Neuralgia and Persistent Idiopathic Facial Pain in Afyonkarahisar, Türkiye.

BACKGROUND: Population-based studies examining the prevalence of trigeminal neuralgia (TN) and persistent idiopathic facial pain (PIFP) are rare, and data on TN prevalence in Türkiye are very limited, with the prevalence of PIFP being unknown. This study aimed to determine the prevalence of TN and PIFP in Türkiye. MATERIALS AND METHODS: This population-based epidemiological study has a cross-sectional and descriptive design, and it was carried out in Afyonkarahisar, Türkiye. Participants aged 18 years and older were screened by using a self-assessment form to determine potential patients with TN or PIFP. RESULTS: A total of 19,237 individuals were included in this study, of which 17,223 responded to the survey questions. TN was diagnosed in 17 individuals, and the prevalence of TN was calculated as 98.5 per 100,000. PIFP was diagnosed in 35 patients, and the prevalence of PIFP was calculated as 202 per 100,000. The mean age of the patients with TN was 54.29 ± 12.98 years, the mean age of patients with PIFP was 49.80 ± 16.10 years, and the female-to-male ratio was 1.13/1 for TN and 2.18/1 for PIFP. CONCLUSION: The prevalence of PIFP in Türkiye has been reported for the first time by this study. Additionally, a much higher prevalence of TN was found when compared to previous study.

Elevated pain sensitivity is associated with reduced rapid eye movement (REM) sleep in females with comorbid temporomandibular disorder and insomnia.

OBJECTIVE: Patients with chronic pain disorders, including Temporomandibular Disorders (TMDs) endorse high levels of sleep disturbances, frequently reporting reduced sleep quality. Despite this, little is known about the effect that daytime pain has on the microstructure and macro-architecture of sleep. Therefore, we aimed to examine the extent to which daytime pain sensitivity, measured using quantitative sensory testing (QST), is associated with objective sleep parameters the following night, including sleep architecture and power spectral density, in women with TMD. METHODS: 144 females with myalgia and arthralgia by examination using the Diagnostic criteria for TMD completed a comprehensive QST battery consisting of General Pain Sensitivity, Central Sensitization Index, and Masseter Pressure Pain Threshold assessments. Polysomnography was collected the same night to measure sleep architecture and calculate relative power in delta, theta, alpha, sigma, and beta power bands. RESULTS: Central Sensitization (B = -3.069, P = .009), General Pain Sensitivity Indices (B = -3.069, P = .007), and Masseter Pain Pressure Threshold (B = 0.030, P = .008) were significantly associated with lower REM% both before and after controlling for covariates. Pain sensitivity measures were not significantly associated with relative power in any of the spectral bands nor with any other sleep architectural stages. CONCLUSIONS: Our findings demonstrate that higher generalized pain sensitivity, masseter pain pressure threshold, as well as central sensitization were associated with a lower percentage of REM in participants with myofascial pain and arthralgia of the masticatory system. These findings provide an important step toward understanding the mechanistic underpinnings of how chronic pain interacts with sleep physiology.

Obstructive sleep apnea treatment improves temporomandibular disorder pain.

PURPOSE: The existence of a bidirectional relationship between poor sleep and pain intensity has been studied, and good sleep quality has been found to be a key factor underlying pain control. The purpose of this prospective cohort study was to observe if OSA treatment provides a reduction in temporo-mandibular disorder (TMD) pain and headache attributed to TMD in patients with obstructive sleep apnea (OSA) after 18 months of OSA treatment. METHODS: A prospective cohort study was conducted on consecutive patients suffering from OSA. Patients underwent polysomnography and TMD examination according to the DC/TMD protocol at baseline and after 18 months. Intensity of TMD pain and headache attributed to TMD were analyzed. RESULTS: Of 40 patients (31 men, mean age 51.3 ± 10.3 years), 33 underwent OSA treatment. At the follow-up examination after 18 months, significant improvements in the intensity of pain-related TMD and headache attributed to TMD were observed (p < 0.05). Seven patients did not start treatment for OSA or discontinued treatment. These patients did not show any significant difference in intensity of TMD-pain or headache attributed to TMD after 18 months (p > 0.05). CONCLUSIONS: Significant reductions in intensity of pain-related TMD and headache attributed to TMD were observed in patients with OSA after 18 months of OSA treatment onset, while no difference was observed in subjects not undergoing or discontinuing OSA treatment. TRIAL REGISTRATION: The protocol was registered on ClinicalTrials.gov database with number NCT04948541.

A critical look at outcome measures: Comparison between four dental research journals by use of a hierarchical model.

AIM: To assess the status quo of outcome measures used in treatment studies in Endodontics, and potentially identify strategies for improvement, by (i) systematically assessing the outcome measures using a conceptual model and (ii) comparing these with measures used in corresponding studies in the adjacent fields. METHODOLOGY: The International Endodontic Journal, Caries Research, The Journal of Clinical Periodontology and The Journal of Oral & Facial Pain and Headache were selected to cover four adjacent dental disciplines. In each journal, the 50 most recent consecutive publications fulfilling inclusion criteria were included. A hierarchical model for diagnostic imaging studies was modified to assess studies related to treatment. The model comprised six levels, with technical as the lowest level and societal as the highest. Extracted data included study origin, study type, and identified outcome measures. Fisher's Exact Tests with Bonferroni corrections compared studies. p < .05 was considered statistically significant. RESULTS: Amongst 756 publications, the 200 most recent studies matching the inclusion criteria were identified. Less than half (36.5%) assessed the clinical, patient, or societal aspects of treatment; 10.0% in International Endodontic Journal, 28.0% in Caries Research, 38.0% in Journal of Clinical Periodontology, and 70.0% in Journal of Oral & Facial Pain and Headache (p < .001). CONCLUSIONS: According to included publications, research on treatment within the endodontic field is mainly focusing on technical and biological outcomes. The benefits of patients and society were less frequently examined than in corresponding journals in adjacent disciplines. When designing studies, including higher-level outcomes should be considered.

Whiplash trauma did not predict jaw pain after 2 years: an explorative study.

OBJECTIVES: To explore predictive factors for the development and maintenance of jaw pain over a 2-year period. METHODS: One hundred nineteen cases (73 women) and 104 controls (59 women), mean age 34.9 years (SD 13.9), attended baseline and 2-year follow-up examinations. The whiplash cases visited the emergency department at Umeå University Hospital, Sweden, with neck pain within 72 h following a car accident, and baseline questionnaires were answered within a month after trauma. Controls were recruited via advertising. Inclusion criteria were age 18-70 years, living in Umeå municipality and Swedish speaking. The exclusion criterion was neck fracture for cases and a previous neck trauma for controls. Validated questionnaires recommended in the standardized Research Diagnostic Criteria for temporomandibular disorders were used. Jaw pain was assessed by two validated screening questions answered with "yes" or "no." A logistic regression analysis was used to predict the outcome variable jaw pain (yes/no) after 2 years. RESULTS: Whiplash trauma did not increase the odds of development of jaw pain over a 2-year period (OR 1.97, 95% CI 0.53-7.38). However, non-specific physical symptoms (OR 8.56, 95% CI 1.08-67.67) and female gender (OR 4.89, 95% CI 1.09-22.02) did increase the odds for jaw pain after 2 years. CONCLUSION: The development and maintenance of jaw pain after whiplash trauma are primarily not related to the trauma itself, but more associated with physical symptoms. CLINICAL RELEVANCE: The development of jaw pain in connection with a whiplash trauma needs to be seen in a biopsychosocial perspective, and early assessment is recommended.

Self-reported bruxism in patients with post-traumatic stress disorder.

OBJECTIVE: The present study aimed to investigate the association between self-reported awake/sleep bruxism, and orofacial pain with post-traumatic stress disorder (PTSD). METHODS: A case-control study with a convenience sample was designed. Participants were recruited from a university-based Trauma Ambulatory. The diagnosis of PTSD was established through a clinical interview and the Structured Clinical Interview (SCID-I/P). Thirty-eight PTSD patients and 38 controls completed the Research Diagnostic Criteria for Temporomandibular Disorders Axis-II to categorize awake/sleep bruxism and orofacial pain. Following this, we performed a short clinical examination of the temporomandibular joint and extraoral muscles. RESULTS: Adjusted logistic regression analysis showed that awake bruxism was associated with PTSD (OR = 3.38, 95% CI = 1.01-11.27, p = 0.047). Sleep bruxism was not associated with any covariate included in the model. In a Poisson regression model, PTSD (IRR = 3.01, 95% CI = 1.38-6.55, p = 0.005) and the muscle pain/discomfort (IRR = 5.12, 95% CI = 2.80-9.36, p < 0.001) were significant predictors for current orofacial pain. CONCLUSIONS: PTSD was associated with self-reported awake bruxism and low-intensity orofacial pain. These conditions were frequent outcomes in patients previously exposed to traumatic events. CLINICAL RELEVANCE: We suggest including a two-question screening for bruxism in psychiatry/psychology interviews to improve under-identification and to prevent harmful consequences at the orofacial level.

Beta Oscillations in the Sensory Thalamus During Severe Facial Neuropathic Pain Using Novel Sensing Deep Brain Stimulation.

OBJECTIVE: Advancements in deep brain stimulation (DBS) devices provide a unique opportunity to record local field potentials longitudinally to improve the efficacy of treatment for intractable facial pain. We aimed to identify potential electrophysiological biomarkers of pain in the ventral posteromedial nucleus (VPM) of the thalamus and periaqueductal gray (PAG) using a long-term sensing DBS system. MATERIALS AND METHODS: We analyzed power spectra of ambulatory pain-related events from one patient implanted with a long-term sensing generator, representing different pain intensities (pain >7, pain >9) and pain qualities (no pain, burning, stabbing, and shocking pain). Power spectra were parametrized to separate oscillatory and aperiodic features and compared across the different pain states. RESULTS: Overall, 96 events were marked during a 16-month follow-up. Parameterization of spectra revealed a total of 62 oscillatory peaks with most in the VPM (77.4%). The pain-free condition did not show any oscillations. In contrast, ß peaks were observed in the VPM during all episodes (100%) associated with pain >9, 56% of episodes with pain >7, and 50% of burning pain events (center frequencies: 28.4 Hz, 17.8 Hz, and 20.7 Hz, respectively). Episodes of pain >9 indicated the highest relative ß band power in the VPM and decreased aperiodic exponents (denoting the slope of the power spectra) in both the VPM and PAG. CONCLUSIONS: For this patient, an increase in ß band activity in the sensory thalamus was associated with severe facial pain, opening the possibility for closed-loop DBS in facial pain.

Bruxism and oro-facial pain not related to temporomandibular disorder conditions: Comorbidities or risk factors?

INTRODUCTION: Bruxism has historically been of particular interest to the field of dentistry, primarily due to the inferred damage it may cause to the dentition and supporting periodontal structures. The definition of bruxism itself has undergone multiple changes over time. In addition, the effects of bruxism as it relates to oro-facial pain conditions has remained a debatable topic. PURPOSE: To review the available literature relating to bruxism and non-temporomandibular disorder (TMD) pain conditions. METHODS: A literature search was conducted with the assistance of an expert librarian. The following databases were reviewed: PubMed, MEDLINE, EMBASE and Google Scholar. For additional references, articles were also retrieved by hand search from the selected papers. Any articles that were not published in English, or the focus were related to temporomandibular disorders were excluded. CONCLUSIONS: While bruxism and certain headache conditions do tend to occur together frequently, evidence relating to any clear common pathophysiological mechanism has yet to be fully elucidated. Robust evidence as it relates to the relationship between bruxism and other non-TMD oro-facial pains is also lacking.

Pleasantness and unpleasantness in somatosensory investigation.

BACKGROUND: Qualitative sensory testing (QualST) is a simple, standardised, chairside method for evaluating somatosensory function; however, testing focuses on detection of cold, touch and pain with no recognition of perceptions of pleasantness and unpleasantness. OBJECTIVES: The study aimed to utilise the stimuli in QualST, with the addition of a soft brush, to investigate stimulus-evoked perceptions of pleasantness and unpleasantness on the facial skin and if any side-to-side differences. Additional aims were to determine the inter- and intra-rater reliability using the modified QualST protocol and in the side-to-side differences. METHODS: Thirty healthy adult female participants underwent three sessions of sensitivity testing as per the modified QualST protocol. Stimuli were applied bilaterally to the facial skin, and participants provided separate yes/no responses for presence of stimulus-evoked pleasantness, unpleasantness and/or differences between sides. RESULTS: The stimuli were able to evoke sensations of pleasantness and unpleasantness with little differences in responses between the Q-tip and goat hair brush for the perceptions. Side-to-side differences in evoked perceptions were observed and greatest, when evaluating for pinprick-evoked unpleasantness (range between sessions = 18-19 participants). Acceptable percentage (≥90%) and excellent Cohen's Kappa (≥0.762) inter- and intra-rater agreements were identified for one or more positive responses for each stimulus modality and the targeted perception. CONCLUSION: The modified QualST protocol provides a simple, reproducible method for the investigation of perceptions of pleasantness and unpleasantness, with readily accessible instrumentation to dental professionals and allowing for a more holistic approach in somatosensory testing.

Smartphone application to report awake bruxism: Development and testing of the Swedish version and a pilot study to evaluate family history in young adults and their parents.

BACKGROUND: Together with psychosocial and hereditary factors, bruxism is a possible risk factor for orofacial pain. Bruxism is defined as a masticatory muscle activity characterized by repetitive or sustained tooth contact, or by bracing or thrusting of the mandible. A smartphone application to report awake bruxism (AB) has been developed and translated into more than 25 languages. OBJECTIVE(S): To translate the application into Swedish, adapt it to Swedish culture and conduct a study to evaluate the usability of the application for studies on family history and associated risk factors. METHODS: Translation and cultural adaption of the Swedish version of the application (BruxApp) was carried out in a four-step sequential process. Ten young adults (22-30 years) were recruited together with ten parents (42-67 years) and reported their AB with the application over two seven-day periods. Pain, stress and parafunctional behaviours were assessed by questionnaires. RESULTS: The back translation check showed minimal discrepancies between the translation and the English version. Participants did not report any problems with the application. Response rates for both groups were 65%. A difference in frequency of AB was shown between young adults and parents (22.0% vs. 12.5%, p < .001). A positive moderate correlation was found between AB and stress (r = 0.54, p = .017). CONCLUSION: The use of application strategies enables data collection on AB which can be used in both clinical and research settings. The results suggest that the Swedish version is ready for implementation and for studies on the relationships between AB, family history and psychosocial factors.

How do the mindfulness and sensory-behavioural-emotional aspects influence the painful experience related to temporomandibular disorder?

BACKGROUND: Chronic pain is persistent or recurrent pain lasting longer than 3 months. The experience of temporomandibular disorder (TMD)-related pain is modulated by emotional and social factors, with mindfulness encapsulating these aspects. OBJECTIVE: To investigate the association between cognitive-behavioural-emotional characteristics, mindfulness and the painful experience in women with chronic pain-related TMD. METHODS: A cross-sectional study was conducted, including 90 women aged between 18 and 61 years old, diagnosed with chronic pain-related TMD according to the Diagnostic Criteria for Temporomandibular Disorder, considering both temporomandibular joint and muscle pain. Specific instruments were employed to assess cognitive-behavioural-emotional aspects. The Mindful Attention Awareness Scale and the Five Facets of Mindfulness Questionnaire scales evaluated the level and construct of mindfulness. The relationship between variables was analysed using bivariate association tests (.05 > p < .20), followed by multiple regression tests (p < .05). RESULTS: The heightened experience of pain correlated with increasing age, a low level of education, the attribution of the locus of control by chance, and lower levels of mindfulness (p < .05). The heightened experience of pain was negatively influenced by mindfulness levels (p < .05). On the other hand, the painful experience was mainly influenced by facets describing negative formulation, distraction, non-reactivity and non-judgement (p < .05). CONCLUSION: Demographic, cognitive-behavioural-emotional data and levels of mindfulness and its facets presented different influence weights on the painful experience. These findings provide support for future studies focusing on mindfulness strategies, education and pain management in women with chronic pain-related TMD.

Reliability of an intraoral extension for intraoral palpation and assessment of mechanical sensitivity of the temporal tendon.

BACKGROUND: The temporal tendon is a structure often compromised in patients suffering from temporomandibular disorders (TMD), yet its intraoral location makes a standardised assessment difficult. OBJECTIVES: To evaluate the variability and accuracy to target force of a newly designed intraoral extension for a palpometer device (Palpeter, Sunstar Suisse) when compared to manual palpation, in addition to clinically assessing the mechanical sensitivity and referred sensations of the temporal tendon in healthy individuals. METHODS: Experiment 1: 12 individuals were asked to target on a scale 0.5, 1 and 2 kg, for 2 and 5 s by using five different methods (Palpeter, Palpeter with three different extension shapes and manual palpation). Experiment 2: 10 healthy participants were recruited for a randomised double-blinded assessment by applying pressure of 0.5, 1 and 2 kg to the right temporal tendon with the three extensions and manual palpation. Participants rated the intensity of their sensation/pain on a 0-50-100 numeric rating scale (NRS), unpleasantness on a 0-100 NRS, and if present, they rated and drew the location of referred sensations. Repeated measures analysis of variance (ANOVA) was used in both experiments to compare differences between palpation methods. Tukey's HSD tests were used for the post hoc comparisons, and p values below .05 were considered significant. RESULTS: Experiment 1: The extensions showed no significant differences between them regarding reliability and accuracy for all forces and durations (p > .05). The manual method was significantly less reliable and accurate when compared to the other methods (p < .05). Experiment 2: There were no significant differences between the Palpeter extensions regarding pain intensity or unpleasantness NRS scores (p > .05), but all the extensions had significantly increased pain intensity and unpleasantness when compared to manual palpation (p < .05). Similarly, the frequency of referred sensations was similar between extensions but increased when compared to manual palpation. CONCLUSIONS: The new Palpeter extensions proved to be significantly more accurate and have lower test-retest variability than the manual method in a non-clinical setting. Clinically, they showed no significant differences in NRS scores for pain intensity nor unpleasantness, with no major differences in referred sensations, making any of the extensions suitable for clinical testing of the temporal tendon in future studies.

Constructing the brief diagnostic criteria for temporomandibular disorders (bDC/TMD) for field testing.

BACKGROUND: Despite advances in temporomandibular disorders' (TMDs) diagnosis, the diagnostic process continues to be problematic in non-specialist settings. OBJECTIVE: To complete a Delphi process to shorten the Diagnostic Criteria for TMD (DC/TMD) to a brief DC/TMD (bDC/TMD) for expedient clinical diagnosis and initial management. METHODS: An international Delphi panel was created with 23 clinicians representing major specialities, general dentistry and related fields. The process comprised a full day workshop, seven virtual meetings, six rounds of electronic discussion and finally an open consultation at a virtual international symposium. RESULTS: Within the physical axis (Axis 1), the self-report Symptom Questionnaire of the DC/TMD did not require shortening from 14 items for the bDC/TMD. The compulsory use of the TMD pain screener was removed reducing the total number of Axis 1 items by 18%. The DC/TMD Axis 1 10-section examination protocol (25 movements, up to 12 sets of bilateral palpations) was reduced to four sections in the bDC/TMD protocol involving three movements and three sets of palpations. Axis I then resulted in two groups of diagnoses: painful TMD (inclusive of secondary headache), and common joint-related TMD with functional implications. The psychosocial axis (Axis 2) was shortened to an ultra-brief 11 item assessment. CONCLUSION: The bDC/TMD represents a substantially reduced and likely expedited method to establish (grouping) diagnoses in TMDs. This may provide greater utility for settings requiring less granular diagnoses for the implementation of initial treatment, for example non-specialist general dental practice.

Attention-deficit hyperactivity disorder and psychostimulant use in patients seeking dental care-Associations with common orofacial pain complaints.

BACKGROUND: Dental medicine should expand its scope to properly assess medical and psychosocial factors that might have an impact on patients' oral health. Based on previous literature and clinical experience, attention-deficit/hyperactivity disorder and psychostimulant medications might represent factors associated with orofacial pain symptoms. OBJECTIVE: The aim of the study was to assess whether common orofacial pain complaints such as jaw pain, jaw clicking, teeth clenching and headaches are more prevalent in dental patients who have an ADHD diagnosis and/or use psychostimulant medications. METHODS: Orofacial pain symptoms prevalence was compared among four groups from a sample of new patients seeking dental care at Tufts University School of Dental Medicine (n = 11 699) based on ADHD diagnosis and psychostimulants intake: G1: no ADHD, no stimulants; G2: yes ADHD, yes stimulants; G3: yes ADHD, no stimulants; G4: no ADHD, yes stimulants. RESULTS: In multivariable logistic regression models adjusting for age, gender, tobacco use, and alcohol consumption, significant differences were found for clenching (p < .0001), jaw pain (p < .0001), and headache (p < .0001). Compared to G1, two groups (G2 and G4) exhibited significantly higher odds of clenching and headaches, whereas only G2 exhibited significantly higher odds of jaw pain. CONCLUSIONS: In comparison with patients without ADHD and not taking psychostimulants medications, dental patients using psychostimulants with and without ADHD diagnosis report headaches and teeth clenching more frequently, while jaw pain is reported more frequently only by those taking psychostimulants with an ADHD diagnosis. Further research is necessary to assess the nature of these associations and their clinical relevance.

[Trigeminal neuralgia: drug therapy : The new German guideline]. / Medikamentöse Therapie der Trigeminusneuralgie : Die neue Leitlinie.

Trigeminal neuralgia is characterized by severe, lightning-like attacks of pain, which are mandatory for the diagnosis. The pain typically occurs on one side and is often triggered by simply touching the face, chewing or talking. In acute exacerbations, this can also hinder food and fluid intake, resulting in a life-threatening clinical picture. A distinction is made between classical, secondary and idiopathic trigeminal neuralgia. For the diagnosis of trigeminal neuralgia, the medical history and imaging procedures are key for classification. The only active substances approved for the treatment of trigeminal neuralgia in Germany are carbamazepine and phenytoin, which is why off-label drugs often need to be used if there is no or insufficient effect or inacceptable side effects. Cooperation between research and clinical practice to improve the care of affected patients is therefore essential.

Electrophysiological characterization of a CaV3.1 calcium channel mutation linked to trigeminal neuralgia.

Trigeminal neuralgia is a rare and debilitating disorder that affects one or more branches of the trigeminal nerve, leading to severe pain attacks and a poor quality of life. It has been reported that the CaV3.1 T-type calcium channel may play an important role in trigeminal pain and a recent study identified a new missense mutation in the CACNA1G gene that encodes the pore forming α1 subunit of the CaV3.1 calcium channel. The mutation leads to a substitution of an Arginine (R) by a Glutamine (Q) at position 706 in the I-II linker region of the channel. Here, we used whole-cell voltage-clamp recordings to evaluate the biophysical properties of CaV3.1 wild-type and R706Q mutant channels expressed in tsA-201 cells. Our data indicate an increase in current density in the R706Q mutant, leading to a gain-of-function effect, without changes in the voltage for half activation. Moreover, voltage clamp using an action potential waveform protocol revealed an increase in the tail current at the repolarization phase in the R706Q mutant. No changes were observed in the voltage-dependence of inactivation. However, the R706Q mutant displayed a faster recovery from inactivation. Hence, the gain-of-function effects in the R706Q CaV3.1 mutant have the propensity to impact pain transmission in the trigeminal system, consistent with a contribution to trigeminal neuralgia pathophysiology.

Recurrent Painful Ophthalmoplegic Neuropathy: A case report with atypical features and a review of the literature.

INTRODUCTION: Recurrent Painful Ophthalmoplegic Neuropathy, previously known as Ophthalmoplegic Migraine, is a poorly characterized disorder mainly because there are few cases described. We report a new case of Recurrent Painful Ophthalmoplegic Neuropathy and a review of the literature to contribute to increasing the knowledge of the clinical features of this disorder. CASE REPORT AND REVIEW OF LITERATURE: A 45-year-old woman presented with adult-onset recurrent attacks of abducens and oculomotor palsy associated with diplopia followed by headache. Most notably, pain always presented many days after oculomotor impairment, a feature never described in the literature. A diagnosis of possible Recurrent Painful Ophthalmoplegic Neuropathy was made after excluding other possible mimicking disorders. Symptoms usually resolved gradually with corticosteroid therapy, albeit without a clear-cut benefit.Clinical data collected from 1989 to 2022 showed that adult onset in Recurrent Painful Ophthalmoplegic Neuropathy is not uncommon. While III cranial nerve palsy is typical, VI and IV nerve palsy have also been described. PATHOPHYSIOLOGY AND DIAGNOSIS: Several hypotheses have been proposed, including nerve compression, ischemia or inflammation/demyelination, but none has been completely accepted.Diagnosis remains of exclusion; magnetic resonance imaging and blood exams are key in differential diagnosis. CONCLUSIONS: Our case gives us the possibility to expand the clinical features of Recurrent Painful Ophthalmoplegic Neuropathy, also contributing to updating the pathophysiological hypotheses.

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

BACKGROUND: 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. CONCLUSION: 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.

Onabotulinum toxin A block of the sphenopalatine ganglion in patients with persistent idiopathic facial pain: a randomized, triple-blind, placebo-controlled, exploratory, cross-over study.

OBJECTIVE: To investigate the efficacy and safety of injecting onabotulinum toxin A (BTA) towards the sphenopalatine ganglion (SPG) using the MultiGuide® in patients with persistent idiopathic facial pain (PIFP). METHODS: This cross-over, exploratory study compared the injection of 25 units BTA versus placebo in patients who met modified ICDH-3 criteria for PIFP. Daily pain diaries were registered for a 4-week baseline, a 12-week follow-up after each injection, and an 8-week conceptual washout period in between. The primary efficacy endpoint was the change from baseline to weeks 5-8 in average pain intensity using a numeric rating scale. Adverse events were recorded. RESULTS: Of 30 patients who were randomized to treatment, 29 were evaluable. In weeks 5-8, there was no statistically significant difference in average pain intensity between BTA versus placebo (0.00; 95% CI = -0.57 to 0.57) (P = 0.996). Following both BTA and placebo injections, five participants reported at least a 30% reduction in average pain during weeks 5-8 (P = 1.000). No serious adverse events were reported. Post-hoc analyses indicated a possible carry-over effect. CONCLUSIONS: Injection of BTA toward the SPG with the MultiGuide® did not appear to provide a reduction in pain reduction at 5-8 weeks, although this finding may be influenced by a carry-over effect. The injection appears to otherwise be safe and well-tolerated in patients with PIFP.Trial Registration: The study protocol is registered in ClinicalTrial.gov (NCT03462290) and EUDRACT (number: 2017-002518-30).