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.

Masticatory performance in oral function assessment: Alternative methods.

BACKGROUND: Masticatory function declines with age or disease, implicating a poor chewing efficiency and an often-unconscious change for a less healthy, yet easy to chew diet. Timely screening of masticatory function may foster an early-onset diagnosis and potential treatment. The aim of this study was to compare alternative diagnostic tools for masticatory function to a Jelly-scan test. MATERIALS AND METHODS: Patients aged 70 years and older who were hospitalised for rehabilitation were recruited for this study. A total of four different tests for masticatory function were administered. The Japanese Society of Gerodontology glucose extraction test (Jelly-scan) was used as reference to compare a colour-changing gum test (Gum1-colour) as well as a mixing ability test with a visual (Gum2-visual) and opto-electronical (Gum2-digital) analyses. Receiver operating characteristic (ROC) curves were used to establish the discriminative value, kappa-values were used to estimate individual agreements and correlations were verified using Spearman's tests. RESULTS: Sixty-one patients (Men n = 23, Women n = 38) aged 82.4 ± 6.8 years participated in the experiments. The average number of natural teeth was 16.5 ± 10.5, 34.4% of the participants wore removable dentures. For all tests, the sum of sensitivity and specificity was >150%. All test correlated with Jelly-scan (absolute Rho >0.5). With Jelly-scan 51 participants (83.6%) were diagnosed with "masticatory hypofunction". After reducing the cut-off value of the test from 100 mg/dL to 65 mg/dL, only 33 participants (54%) fulfilled the diagnosis. This post-hoc analysis increased the sensitivity of the Gum2-tests and the agreement to kappa >0.5 for all three tests. CONCLUSION: All three tests can be considered useful screening alternatives. In its original version, Jelly-scan may tend to over-diagnose masticatory hypofunction, hence a novel cut-off with better agreement between tests is suggested.

Fit and retention of complete denture bases: Part I - Conventional versus CAD-CAM methods: A clinical controlled crossover study.

STATEMENT OF PROBLEM: Clinical evidence is sparse on whether dentures fabricated by computer-aided design and computer-aided manufacturing (CAD-CAM) methods afford superior fit and retention when compared with those fabricated conventionally. PURPOSE: The purpose of this clinical controlled crossover study was to evaluate the peak retention force and fit of CAD-CAM manufactured (3D-printed and milled) maxillary complete denture bases and conventional heat-polymerized bases (control). MATERIAL AND METHODS: Twenty participants with edentulous maxillary arches were recruited. Impressions were made with a border-molded custom tray, and the resulting definitive cast was scanned. The conventional base was manufactured on the definitive cast with a hook and a 45-degree platform with a central notch and 2 lateral notches. The scan of the definitive cast was used for the fabrication of a milled and a printed base. The platform and hook position on the conventional base were transferred digitally to the milled and printed bases. All bases were scanned. A traction dynamometer was orientated into the notches, and retention was evaluated in the post dam and tuberosity areas. Scans were imported into a comparison software program which matched scans to their corresponding reference and performed a 3-dimensional comparison. The Friedman and Wilcoxon tests were used to compare between groups (confidence interval: 95%, α=.05). RESULTS: Nineteen participants with a mean ±standard deviation age of 64.1 ±14.7 years completed all clinical sessions. No significant difference in peak retention was measured between milled (MB1), printed (PB1), and conventional (CB) bases in the post dam (CB: 12.44 ±9.62 N, PB1: 16.08 ±15.28 N, MB1: 14.52 ±17.07 N) and right tuberosity area (CB: 8.99 ±7.82 N, PB1: 11.28 ±9.57 N, MB1: 11.99 ±12.10 N). In the left tuberosity area, peak retention was lower for CB (10.03 ±8.39 N) than PB1 (14.98 ±14.72 N) and MB1 (13.55 ±15.53 N; P=.05). Compared with the definitive cast, the fit of the conventional base (0.18 ±0.01 mm) was closer than the printed (0.21 ±0.03 mm) and milled bases (0.21 ±0.02 mm) (P<.001). CONCLUSIONS: The CD bases manufactured by CAD-CAM techniques provided retention and fit similar to that of conventionally manufactured bases and can therefore be considered suitable techniques.

Fit and retention of complete denture bases: Part II - conventional impressions versus digital scans: A clinical controlled crossover study.

STATEMENT OF PROBLEM: Although the intraoral scanning of edentulous ridges is feasible, clinical evidence that the resulting denture retention is equivalent to that achieved with conventional impressions is lacking. PURPOSE: The purpose of this clinical study was to determine the retention of complete denture bases fabricated from digital intraoral scans versus conventional impressions by using border molding and posterior palatal seal compression. MATERIAL AND METHODS: Twenty volunteers with an edentulous maxilla were recruited. An intraoral scan of the maxilla and a conventionally border-molded impression with a custom tray were made. The conventional impression was poured; the definitive cast was scanned. Three-dimensionally (3D) printed (PB1) and milled bases (MB1) were fabricated based on the scan of the definitive cast. Based on the intraoral scan, a 3D-printed (PB2) and a milled base (MB2) were fabricated. On each base, a platform with a hook consisting of a central notch orienting the force against the post dam (PD) and 2 lateral notches orienting the forces against the left (LT) and right (RT) tuberosities was set in the center of the outer surface of the base. A traction dynamometer was inserted in the hook and oriented into the corresponding notch by applying force until dislodgement. All bases were subsequently stored in artificial saliva for 2 weeks and scanned. Retention testing was repeated by using the same procedure. To evaluate trueness and to visualize the differences on a color map, the scan of the definitive cast and the intraoral scans were matched and compared in 3 dimensions. The Wilcoxon tests were used to compare the retention of the different bases (95% confidence interval, α=.05). RESULTS: Nineteen participants with a mean ±standard deviation age of 64.1 ±14.7 years completed the 4 study sessions. The retention of printed bases (PD: 16.08 ±15.28 N; LT: 14.98 ±14.72 N; RT: 11.28 ±9.57 N) and milled bases (PD:14.52 ±17.07 N; RT: 11.99 ±12.10 N; LT: 13.55 ±15.53 N) fabricated from conventional impressions presented significantly higher retentive forces than those printed (PD: 6.21 ±4.72 N; RT:5.12 ±2.78 N; LT: 4.45 ±2.77 N) and milled (PD: 6.58 ±4.92 N; RT: 4.65 ±2.63 N; LT: 5.02 ±3.58 N) from the intraoral scans (P<.05). The differences were significant in all directions of dislodgement, as well as after storage in artificial saliva for 2 weeks. Comparison of the 3D distances between the intraoral scan and the definitive cast revealed a mean deviation of 0.45 ±0.11 mm. CONCLUSIONS: Conventional impressions of the edentulous maxilla, including the clinical steps of border molding and posterior palatal seal compression, provide better retention than digital intraoral scans with both milled and 3D-printed denture bases.

Oral function and nutritional status in non-acute hospitalised elders.

INTRODUCTION: Malnutrition and risk of malnutrition continues to be a common finding in elders, yet its association with oral function in hospitalised patients remains unclear. MATERIAL AND METHODS: Patients aged 70 years or over who had been hospitalised for non-acute rehabilitation were recruited. Nutritional risk was screened using the Mini-Nutritional Assessment Short Form (MNA-SF) and Nutritional Risk Screening (NRS) scores. Malnutrition was assessed according to the Global Leadership Initiative on Malnutrition (GLIM) criteria. All participants underwent the oral hypofunction test battery, evaluating oral hygiene, oral dryness, occlusal force, tongue-lip motor function, tongue pressure, masticatory and swallowing function. Statistical analyses comprised Mann-Whitney or Kruskal-Wallis tests. Bivariate associations between categorical variables were tested using the Pearson chi-square test; for continuous variables, the Spearman correlation was calculated. A P-value < .05 was considered statistically significant. RESULTS: Sixty patients aged a mean 82.5 ± 7.0 years participated. Some 88.3% were diagnosed with oral hypofunction, and this was more common in older patients (P = .020). Analysing the 7 oral hypofunction tests as an interval variable (NiOF) revealed additional correlations with number of teeth (ρ = 0.477) as well as the nutritional risk, evaluated by the MNA-SF (ρ = -0.284) and NRS (ρ = 0.317) scores. NiOF scores were higher among denture wearers (P = .003). GLIM did not confirm the correlation with NiOF. Biomarkers such as serum albumin and CRP were not associated with the NiOF score. CONCLUSION: In this sample, the association between oral function and nutritional state is more obvious in nutritional risk scores than in the malnutrition diagnosis by GLIM.

Pancreas stiffness in liver cirrhosis is an indicator of insulin secretion caused by portal hypertension and pancreatic congestion.

AIM: Portal hypertension induces pancreatic congestion and impaired insulin secretion in patients with liver cirrhosis (LC). However, its mechanism is unclear, with no established noninvasive imaging method for the evaluation of its pathogeneses. The present study focused on pancreas stiffness, as assessed by shear wave elastography (SWE), and examined its association with portal hypertension and insulin secretion. METHODS: Shear wave elastography and contrast-enhanced ultrasonography were utilized to evaluate pancreas stiffness and congestion, respectively. A glucagon challenge test was used for insulin secretion assessment. Furthermore, rat models of carbon tetrachloride (CCl4 )-induced LC and portal hypertension were used to identify the direct effects of pancreatic congestion. Immunohistochemistry staining of the pancreas was carried out on human autopsy samples. RESULTS: Pancreas stiffness measured by SWE was higher in patients with LC than in controls and showed significant correlation with pancreatic congestion. The glucagon challenge test indicated a lower value for the change in C-peptide immunoreactivity in the LC group, which was inversely correlated with pancreas stiffness and congestion. Additionally, portal hypertension and insulin secretion dysfunction were confirmed in CCl4 rat models. Autopsy of human samples revealed congestive and fibrotic changes in the pancreas and the relationship between insulin secretion and their factors in patients with LC. CONCLUSIONS: In patients with LC, pancreas stiffness measured by SWE could be a potential noninvasive test for evaluating pancreatic congestion and fibrosis due to portal hypertension. Moreover, it was associated with impaired insulin secretion, and could aid in guiding the treatment for hepatogenous diabetes.

Variability in tongue pressure among elderly and young healthy cohorts: A systematic review and meta-analysis.

OBJECTIVES: Tongue pressure (TP) is used for the diagnosis of oral hypofunction; however, the impact of several variables on TP is unclear. Therefore, the current systematic review and meta-analysis aimed to analyse the variability in tongue pressure among healthy individuals aged ≥60 years vs <60 years. Secondary outcomes were the influence of gender and the type of measuring device (Iowa Oral Performance Instrument (IOPI) vs JMS tongue pressure measurement device (JMS)). METHODS: PubMed and the Japanese database Ichushi-Web were searched systematically by two independent reviewers for studies reporting TP values in healthy populations. Clinical studies published between 1959 and June 2020 with more than 10 participants, written in English, German or Japanese, were included. A random-effects meta-regression for aggregate-level data was applied (α < 0.05). RESULTS: Sixty-eight studies reported TP for a total of 13 773 subjects aged <60 years (n = 3265) and ≥60 years (n = 10 508). TP was significantly higher in subjects <60 years (estimated weighted mean (EWM) ± standard error = 51.9 ± 1.28 kPa; 95% CI = 49.4-54.4) relative to those ≥60 (EWM = 34.7 ± 0.94 kPa; 95% CI = 32.8-36.5) (P < .001), men (EWM = 45.9 ± 2.09 kPa; 95% CI = 41.8-50.0) relative to women (EWM = 39.3 ± 1.68 kPa; 95% CI = 36.0-42.6) (P = .015) and when assessed with the IOPI (EWM = 51.9 ± 1.32 kPa; 95% CI = 49.3-54.5) compared to the JMS (EWM = 33.5 ± 0.63 kPa; 95% CI = 32.2-34.7) (P < .001). In terms of gender, there was no significant difference in TP among subjects ≥60 years (P = .282). However, in subjects younger than 60, a significant difference was observed (P = .004). CONCLUSIONS: Healthy populations aged <60 years showed significantly higher TP than those aged ≥60 years. TP values ascertained by the IOPI are significantly higher than those obtained with the JMS.

Validation of a novel diagnostic tool for decreased tongue pressure.

INTRODUCTION: Reduced tongue pressure may render eating and swallowing difficult. The purpose of this study was to investigate whether the tongue training device can also be used as a diagnostic device and whether its sensitivity and specificity are equal to the numerical tongue pressure measuring device. MATERIAL AND METHODS: The target group is patients aged 70 years and over who are hospitalised for rehabilitation. Tongue pressure was measured by both, a tongue pressure measuring instrument and a tongue training tool. The diagnosis of the reduced tongue pressure was made with the tongue pressure measuring instrument and set the verified with the novel tongue training tool. RESULTS: Sixty-two participants were included in the study. Forty-five were classified by the tongue pressure measuring device and 53 by the tongue training device as 'low tongue pressure'. Spearman correlation confirmed a positive correlation between the tongue pressure measuring device and the tongue training device rs  = 0.800, p = 0.01 level (2-tailed). The tongue training device test identified sensitivity was 100%, and its specificity was 52.9%. The AUC of the ROC curve is 0.901. CONCLUSION: The tongue training device seems a simple, safe and readily available alternative to the tongue pressure measuring device for the diagnosis of low tongue pressure, with an excellent sensitivity and very good specificity.

Developing a research diagnostic criteria for burning mouth syndrome: Results from an international Delphi process.

OBJECTIVE: To develop a beta version of a preliminary set of empirically derived research diagnostic criteria (RDC) for burning mouth syndrome (BMS) through expert consensus, which can then be taken into a test period before publication of a final RDC/BMS. DESIGN: A 6 round Delphi process with twelve experts in the field of BMS was used. The first round formed a focus group during which the purpose of the RDC and the definition of BMS was agreed upon, as well as the structure and contents. The remaining rounds were carried out virtually via email to achieve a consensus of the beta version of the RDC/BMS. RESULTS: The definition of BMS was agreed to be 'an intraoral burning or dysaesthetic sensation, recurring daily for more than 2 hours per day over more than 3 months, without evident causative lesions on clinical examination and investigation'. The RDC was based upon the already developed and validated RDC/TMD and formed three main parts: patient self-report; examination; and psychosocial self-report. A fourth additional part was also developed listing aspirational biomarkers which could be used as part of the BMS diagnosis where available, or to inform future research. CONCLUSION: This Delphi process has created a beta version of an RDC for use with BMS. This will allow future clinical research within BMS to be carried out to a higher standard, ensuring only patients with true BMS are included. Further validation studies will be required alongside refinement of the RDC as trialling progresses.

Endoscopic stent placement above the sphincter of Oddi for biliary strictures after living donor liver transplantation.

BACKGROUND: Endoscopic balloon dilation and/or plastic stent placement has been a standard method for treating biliary strictures complicated post living donor liver transplantation (LDLT). The strictures may be refractory to endoscopic treatment and require long-term stent placement. However, consensus on the optimal period of the stent indwelling and usefulness of the inside stent does not exist. METHODS: We evaluated the long-term efficacy of stent treatment in patients with biliary stricture post LDLT. In addition, we compared the stent patency between inside stent and conventional outside stent. RESULTS: A total of 98 ERC sessions (median 6: range 1-14) performed on 16 patients receiving endoscopic treatment for biliary strictures post LDLT with duct-to-duct biliary reconstruction were analyzed. Biliary strictures successfully treated in 14 patients (88%) included 7 patients (44%) showing improvement of biliary strictures with repeated endoscopic stent placement. Stent replacement was carried out every 6 to 12 months for the remainder 7 patients (44%). Biliary stents were placed in 87 sessions (77 inside sessions and 10 outside sessions). Stent migration occurred 13 times (16%) and none of the inside stent sessions and the outside stent sessions, respectively. Median patency of inside stent and outside stent were 222 days (range; 8-1736) and 99 days (range; 7-356), respectively. The stent occlusion was significantly less in inside stent than in outside stent (p < 0.001). Stone formation was observed in 14 (18%) of the inside stent and 3 (30%) of the outside stent. Biliary stones were small and successfully removed endoscopically. CONCLUSIONS: The endoscopic treatment using inside stent was useful in the management of biliary strictures after LDLT.

Altered pain modulation to noxious heat thermal stimuli in burning mouth syndrome.

OBJECTIVES: The aim of this study was to examine temporal summation (TS) and conditioned pain modulation (CPM) in patients with burning mouth syndrome (BMS) and healthy controls using intra-epidermal electrical stimulation (IES). MATERIALS AND METHODS: Twenty-six female patients with BMS and 27 healthy female controls participated in this study. A single stimulus with electrical stimulation followed by a train of 10 successive stimuli was administered to the right chin of participants in both the BMS and control groups. CPM was evaluated with the changes of TS calculated from the difference in numerical pain scale data between these two test stimuli and the following warm (40°C) and hot (47°C) conditioning stimuli applied at the non-dominant hand in both the BMS and control groups. RESULTS: TS was present in both the BMS and control groups. CPM in the BMS group was significantly less efficient at the 47°C condition than that in the control group, while no significant difference was observed in the CPM between the BMS and the control groups at the 40°C condition. CONCLUSION: These findings indicate that BMS is associated with a deficit inhibitory CPM and implicate the involvement of the central nervous system in the pathophysiology of BMS.

Microglia-Astrocyte Communication via C1q Contributes to Orofacial Neuropathic Pain Associated with Infraorbital Nerve Injury.

Trigeminal nerve injury causes a distinct time window of glial activation in the trigeminal spinal subnucleus caudalis (Vc), which are involved in the initiation and maintenance phases of orofacial neuropathic pain. Microglia-derived factors enable the activation of astrocytes. The complement component C1q, which promotes the activation of astrocytes, is known to be synthesized in microglia. However, it is unclear whether microglia-astrocyte communication via C1q is involved in orofacial neuropathic pain. Here, we analyzed microglia-astrocyte communication in a rat model with infraorbital nerve injury (IONI). The orofacial mechanical hypersensitivity induced by IONI was significantly attenuated by preemptive treatment with minocycline. Immunohistochemical analyses revealed that minocycline inhibited the increase in c-Fos immune-reactive (IR) cells and the fluorescence intensity of both Iba1 and glial fibrillary acidic protein (GFAP) in the Vc following IONI. Intracisternal administration of C1q caused orofacial mechanical hypersensitivity and an increase in the number of c-Fos-IR cells and fluorescence intensity of GFAP. C1q-induced orofacial mechanical hypersensitivity was completely abrogated by intracisternal administration of fluorocitrate. The present findings suggest that the enhancement in the excitability of Vc nociceptive neurons is produced by astrocytic activation via the signaling of C1q released from activated microglia in the Vc following IONI, resulting in persistent orofacial neuropathic pain.

Association of somatosensory dysfunction with symptom duration in burning mouth syndrome.

OBJECTIVES: A standardized battery of quantitative sensory tests developed by the German Research Network on Neuropathic Pain (DFNS) was used to assess the association between somatosensory dysfunction and disease duration in patients with burning mouth syndrome (BMS). MATERIALS AND METHODS: The 28 female participants with BMS were classified according to disease duration: ≤ 6 months (subchronic BMS, n = 15) and > 6 months (chronic BMS, n = 13); 29 age- and sex-matched healthy volunteers (control group) were recruited from staff of a dental hospital. The DFNS quantitative sensory testing protocol was applied at the ulnar surface of the right forearm and the tip of the tongue. Values for BMS patients and controls were compared and analyzed. RESULTS: The mechanical detection threshold (MDT) was significantly higher (i.e., loss of sensation) at the tongue tip in the chronic BMS group than in the control group (p = 0.011), whereas mechanical pain sensitivity (MPS) at the forearm was significantly higher (i.e., gain of sensation) in the chronic BMS group than in the control group (Z score = - 2.13 and 1.99, respectively). Multivariate analyses revealed that BMS patients could be discriminated from controls by using pressure pain threshold at the tongue (79.3%) (in the subchronic BMS group) and by MDT and MPS at the tongue tip and MPS at the forearm (96.6 and 89.7%, respectively) (in the chronic BMS group). CONCLUSIONS: In BMS patients with long disease duration, MDT showed loss of sensation. CLINICAL RELEVANCE: Increased MPS suggests that a neuropathic mechanism in the peripheral and central nervous systems is involved in BMS development.

An updated review on pathophysiology and management of burning mouth syndrome with endocrinological, psychological and neuropathic perspectives.

Burning mouth syndrome (BMS) is a chronic oro-facial pain disorder of unknown cause. It is more common in peri- and post-menopausal women, and sex hormone dysregulation is believed to be an important causative factor. Psychosocial events often trigger or exacerbate symptoms, and persons with BMS appear to be predisposed towards anxiety and depression. Atrophy of small nerve fibres in the tongue epithelium has been reported, and potential neuropathic mechanisms for BMS are now widely investigated. Historically, BMS was thought to comprise endocrinological, psychosocial and neuropathic components. Neuroprotective steroids and glial cell line-derived neurotrophic factor family ligands may have pivotal roles in the peripheral mechanisms associated with atrophy of small nerve fibres. Denervation of chorda tympani nerve fibres that innervate fungiform buds leads to alternative trigeminal innervation, which results in dysgeusia and burning pain when eating hot foods. With regard to the central mechanism of BMS, depletion of neuroprotective steroids alters the brain network-related mood and pain modulation. Peripheral mechanistic studies support the use of topical clonazepam and capsaicin for the management of BMS, and some evidence supports the use of cognitive behavioural therapy. Hormone replacement therapy may address the causes of BMS, although adverse effects prevent its use as a first-line treatment. Selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) may have important benefits, and well-designed controlled studies are expected. Other treatment options to be investigated include brain stimulation and TSPO (translocator protein 18 kDa) ligands.

Effects of surgical treatment for classical trigeminal neuralgia with concomitant persistent facial pain.

PURPOSE: Classical trigeminal neuralgia with concomitant persistent facial pain responds poorly to conservative treatment. The authors describe the effects of microvascular decompression and radiofrequency thermocoagulation for patients with classical trigeminal neuralgia and concomitant persistent facial pain. CASE REPORT: Case 1 was a 61-year-old man with dull, continuous, aching pain in the left maxillary and mandibular molar area. Case 2 was a 68-year-old woman with aching pain in the maxillary right molar. Case 3 was a 67-year-old woman with severe pain in the right upper lip and maxillary right second premolar. Case 4 was a 42-year-old man with orofacial pain of 14 months' duration. Cases 1 and 2 underwent radiofrequency thermocoagulation and reported good relief of symptoms. Cases 3 and 4 underwent microvascular decompression and attained excellent relief. CONCLUSION: Microvascular decompression may be more effective than radiofrequency thermocoagulation for patients with classical trigeminal neuralgia with concomitant persistent facial pain.

Orofacial Pain and Menstrually Related Migraine.

PURPOSE: Migraine is a common, debilitating, primary headache disorder that can cause and be affected by odontalgia. CASE REPORT: A 49-year-old woman(Patient 1) presented with pulsating pain in the left maxillary molar area, and a history of unsuccessful root canal treatment. She was ultimately diagnosed with menstrually related migraine without aura and zolmitriptan was prescribed, which reduced her headache and toothache together. A 45-year-old woman (Patient 2) presented with throbbing pain in the right maxillary molar and cheek area. Past repeated endodontic therapy had been unsuccessful. She was then diagnosed with menstrually related migraine without aura, and sumatriptan significantly reduced her headache and toothache. A 40-year-old woman (Patient 3) presented with pulsating pain near the left maxillary molar region. Pulpectomy was performed after she had previously received a diagnosis of pulpitis in the left maxillary second molar, but her pain did not subside. Patient 2 and 3 were misdiagnosed as pulpitis by dental practitioners and the pain did not relive after pulpectomy. All patients were diagnosed as migraine by headache specialists and were treated with triptans, which resulted in satisfactory pain relief. CONCLUSION: A thorough history and examination, as well as an understanding of migraine headaches, is necessary to differentiate odontogenic pain and migraine headaches. Key Words: menstrually related migraine, orofacial pain, ICHD-3, headache.

Effect of Pregabalin and Diclofenac on tactile allodynia, mechanical hyperalgesia and pro inflammatory cytokine levels (IL-6, IL-1ß) induced by chronic constriction injury of the infraorbital nerve in rats.

The present study evaluated the effects of systemic pregabalin (PG) and diclofenac (Dic) on neuropathic orofacial pain induced by chronic constriction injury (CCI) of the infraorbital nerve (ION) and on the pro-inflammatory cytokines levels in the affected nerve. Fifty-four rats underwent left infra orbital nerve CCI, and 7 days after the procedure as the pain developed, the rats were randomly assigned to one of the treatment groups: PG 300, 30 or 10 mg/kg, Dic 10, 5 or 1 mg/kg or saline group (Sal) (n/group = 8). Addiitonal 8 rats served as naïve control group. Tactile-allodynia and Mechano-hyperalgesia were tested before the surgical procedure and at days 7, 8, and 9 postoperatively. On the 9th day, the rats were euthanized and the affected and contralateral sciatic nerves were harvested to assess IL-6 and IL-1ß nerve levels employing enzyme linked immunosorbent assay (ELISA). Daily injection of PG (all doses) significantly reduced tactile-allodynia and mechano-hyperalgesia (p < .05) while Dic did not. On the 9th day, the ipsilateral nerve IL-6 levels were significantly decreased (p < .05) in the PG and DIC groups compared to the Sal group. IL-1ß levels demonstrated a significant reduction (p < .05) in the PG group when compared to saline. These results suggest that PG but not Dic may be effective in reducing neuropathic orofacial pain. The mechanisms of action may be associated to some extent with reduction in IL-1ß levels in the affected nerve.

Efficacy of chemotherapy in elderly patients with unresectable pancreatic cancer: a multicenter review of 895 patients.

BACKGROUND: The efficacy of chemotherapy for unresectable pancreatic cancer has improved. However, it is occasionally difficult to make treatment decisions for elderly patients. We reviewed the outcomes of elderly patients with unresectable pancreatic cancer by using a large cohort and evaluated whether they had received chemotherapy and the reason why. METHODS: Data for 895 pancreatic cancer patients who were treated using chemotherapy or best supportive care were analyzed considering demographics, clinical stage, treatment, and outcome. Data were analyzed using the chi-square test, Student t-test, or Mann-Whitney U-test, as appropriate. Outcomes were analyzed using the Kaplan-Meier method. Differences in survival were analyzed using the log-rank test. RESULTS: The median survival time was significantly shorter in elderly patients (≥65 years) than in younger patients (<65 years) (181 vs. 263 days, P = 0.0001). The median survival time of patients treated with chemotherapy was not significantly different between the elderly and the younger group (274 days vs. 333 days, P = 0.09), and nor was that of patients choosing best supportive care (84 days vs. 78 days, P = 0.83). These results held true even when the age cut-off between younger and elder patients was increased to 70, 75, and 80 years. Elderly patients treated with chemotherapy had a significantly longer median survival time than those choosing best supportive care (274 vs. 86 days, P < 0.0001); a significantly greater proportion of elderly patients chose best supportive care compared to younger patients (47.8 vs. 25.8%, P < 0.0001). The reason for choosing best supportive care was established in 261 elderly patients (82.9%); 133 (51.0%) met the eligibility criteria for chemotherapy, but of these, 78 (58.6%) were not informed about their disease. The treatment preferences of elderly patients were not always considered; they often received only best supportive care per family members preference (N = 65, 48.8%) or because the physician based their treatment decision only on the patient's age (N = 68, 51.1%). CONCLUSIONS: Chemotherapy appears effective for elderly pancreatic cancer patients with unresectable disease, but treatment needs to be optimized to improve prognosis.

Altered structural connectivity of pain-related brain network in burning mouth syndrome-investigation by graph analysis of probabilistic tractography.

PURPOSE: Burning mouth syndrome (BMS) is a chronic intraoral pain syndrome featuring idiopathic oral pain and burning discomfort despite clinically normal oral mucosa. The etiology of chronic pain syndrome is unclear, but preliminary neuroimaging research has suggested the alteration of volume, metabolism, blood flow, and diffusion at multiple brain regions. According to the neuromatrix theory of Melzack, pain sense is generated in the brain by the network of multiple pain-related brain regions. Therefore, the alteration of pain-related network is also assumed as an etiology of chronic pain. In this study, we investigated the brain network of BMS brain by using probabilistic tractography and graph analysis. METHODS: Fourteen BMS patients and 14 age-matched healthy controls underwent 1.5T MRI. Structural connectivity was calculated in 83 anatomically defined regions with probabilistic tractography of 60-axis diffusion tensor imaging and 3D T1-weighted imaging. Graph theory network analysis was used to evaluate the brain network at local and global connectivity. RESULTS: In BMS brain, a significant difference of local brain connectivity was recognized at the bilateral rostral anterior cingulate cortex, right medial orbitofrontal cortex, and left pars orbitalis which belong to the medial pain system; however, no significant difference was recognized at the lateral system including the somatic sensory cortex. A strengthened connection of the anterior cingulate cortex and medial prefrontal cortex with the basal ganglia, thalamus, and brain stem was revealed. CONCLUSION: Structural brain network analysis revealed the alteration of the medial system of the pain-related brain network in chronic pain syndrome.

ERK-GluR1 phosphorylation in trigeminal spinal subnucleus caudalis neurons is involved in pain associated with dry tongue.

BACKGROUND: Dry mouth is known to cause severe pain in the intraoral structures, and many dry mouth patients have been suffering from intraoral pain. In development of an appropriate treatment, it is crucial to study the mechanisms underlying intraoral pain associated with dry mouth, yet the detailed mechanisms are not fully understood. To evaluate the mechanisms underlying pain related to dry mouth, the dry-tongue rat model was developed. Hence, the mechanical or heat nocifensive reflex, the phosphorylated extracellular signal-regulated kinase and phosphorylated GluR1-IR immunohistochemistries, and the single neuronal activity were examined in the trigeminal spinal subnucleus caudalis of dry-tongue rats. RESULTS: The head-withdrawal reflex threshold to mechanical, but not heat, stimulation of the tongue was significantly decreased on day 7 after tongue drying. The mechanical, but not heat, responses of trigeminal spinal subnucleus caudalis nociceptive neurons were significantly enhanced in dry-tongue rats compared to sham rats on day 7. The number of phosphorylated extracellular signal-regulated kinase-immunoreactive cells was also significantly increased in the trigeminal spinal subnucleus caudalis following noxious stimulation of the tongue in dry-tongue rats compared to sham rats on day 7. The decrement of the mechanical head-withdrawal reflex threshold (HWT) was reversed during intracisternal administration of the mitogen-activated protein kinase kinase 1 inhibitor, PD98059. The trigeminal spinal subnucleus caudalis neuronal activities and the number of phosphorylated extracellular signal-regulated kinase-immunoreactive cells following noxious mechanical stimulation of dried tongue were also significantly decreased following intracisternal administration of PD98059 compared to vehicle-administrated rats. Increased number of the phosphorylated GluR1-IR cells was observed in the trigeminal spinal subnucleus caudalis of dry-tongue rats, and the number of phosphorylated GluR1-IR cells was significantly reduced in PD98059-administrated rats compared to the vehicle-administrated tongue-dry rats. CONCLUSIONS: These findings suggest that the pERK-pGluR1 cascade is involved in central sensitization of trigeminal spinal subnucleus caudalis nociceptive neurons, thus resulting in tongue mechanical hyperalgesia associated with tongue drying.