Temporomandibular disorders cases with high-impact pain are more likely to experience short-term pain fluctuations.

Temporomandibular disorders (TMD) patients can present clinically significant jaw pain fluctuations which can be debilitating and lead to poor global health. The Graded Chronic Pain Scale evaluates pain-related disability and its dichotomous grading (high/low impact pain) can determine patient care pathways and in general high-impact pain patients have worse treatment outcomes. Individuals with low-impact TMD pain are thought to have better psychosocial functioning, more favorable disease course, and better ability to control pain, while individuals with high-impact pain can present with higher levels of physical and psychological symptoms. Thereby, there is reason to believe that individuals with low- and high-impact TMD pain could experience different pain trajectories over time. Our primary objective was to determine if short-term jaw pain fluctuations serve as a clinical marker for the impact status of TMD pain. To this end, we estimated the association between high/low impact pain status and jaw pain fluctuations over three visits (≤ 21-day-period) in 30 TMD cases. Secondarily, we measured the association between jaw pain intensity and pressure pain thresholds (PPT) over the face and hand, the latter measurements compared to matched pain-free controls (n = 17). Jaw pain fluctuations were more frequent among high-impact pain cases (n = 15) than low-impact pain cases (n = 15) (OR 5.5; 95% CI 1.2, 26.4; p value = 0.033). Jaw pain ratings were not associated with PPT ratings (p value > 0.220), suggesting different mechanisms for clinical versus experimental pain. Results from this proof-of-concept study suggest that targeted treatments to reduce short-term pain fluctuations in high-impact TMD pain is a potential strategy to achieve improved patient perception of clinical pain management outcomes.

Prolactin signaling modulates stress-induced behavioral responses in a preclinical mouse model of migraine.

OBJECTIVE: The aim of this study was to determine if prolactin signaling modulates stress-induced behavioral responses in a preclinical migraine model. BACKGROUND: Migraine is one of the most complex and prevalent disorders. The involvement of sex-selective hormones in migraine pathology is highly likely as migraine is more common in women and its frequency correlates with reproductive stages. Prolactin has been shown to be a worsening factor for migraine. Normally prolactin levels are low; however levels can surge during stress. Dopamine receptor agonists, which suppress pituitary prolactin release, are an effective migraine treatment in a subset of patients. Previously, we showed that administration of prolactin onto the dura mater induces female-specific behavioral responses, suggesting that prolactin may play a sex-specific role in migraine. METHODS: The effects of prolactin signaling were assessed using a preclinical migraine model we published recently in which behavioral sensitization is induced by repeated stress. Plasma prolactin levels were assessed in naïve and stressed CD-1 mice (n = 3-5/group) and transgenic mice with conditional deletion of the Prlr in Nav1.8-positive sensory neurons (Prlr conditional knock-out [CKO]; n = 3/group). To assess the contribution of prolactin release during stress, naïve or stressed male and female CD-1 mice were treated with the prolactin release inhibitor bromocriptine (2 mg/kg; n = 7-12/group) or vehicle for 5 days (8-12/group) and tested for facial hypersensitivity following stress. Additionally, the contribution of ovarian hormones in regulating the prolactin-induced responses was assessed in ovariectomized female CD-1 mice (n = 6-10/group). Furthermore, the contribution of Prlr activation on Nav1.8-positive sensory neurons was assessed. Naïve or stressed male and female Prlr CKO mice and their control littermates were tested for facial hypersensitivity (n = 8-9/group). Immunohistochemistry was used to confirm loss of Prlr in Nav1.8-positive neurons in Prlr CKO mice. The total sample size is n = 245; the full analysis sample size is n = 221. RESULTS: Stress significantly increased prolactin levels in vehicle-treated female mice (39.70 ± 2.77; p < 0.0001). Bromocriptine significantly reduced serum prolactin levels in stressed female mice compared to vehicle-treated mice (-44.85 ± 3.1; p < 0.0001). Additionally, no difference was detected between female stressed mice that received bromocriptine compared to naïve mice treated with bromocriptine (-0.70 ± 2.9; p = 0.995). Stress also significantly increased serum prolactin levels in male mice, although to a much smaller extent than in females (0.61 ± 0.08; p < 0.001). Bromocriptine significantly reduced serum prolactin levels in stressed males compared to those treated with vehicle (-0.49 ± 0.08; p = 0.002). Furthermore, bromocriptine attenuated stress-induced behavioral responses in female mice compared to those treated with vehicle (maximum effect observed on day 4 post stress [0.21 ± 0.08; p = 0.03]). Bromocriptine did not attenuate stress-induced behavior in males at any timepoint compared to those treated with vehicle. Moreover, loss of ovarian hormones did not affect the ability of bromocriptine to attenuate stress responses compared to vehicle-treated ovariectomy mice that were stressed (maximum effect observed on day 4 post stress [0.29 ± 0.078; p = 0.013]). Similar to CD-1 mice, stress increased serum prolactin levels in both Prlr CKO female mice (27.74 ± 9.96; p = 0.047) and control littermates (28.68 ± 9.9; p = 0.041) compared to their naïve counterparts. There was no significant increase in serum prolactin levels detected in male Prlr CKO mice or control littermates. Finally, conditional deletion of Prlr from Nav1.8-positive sensory neurons led to a female-specific attenuation of stress-induced behavioral responses (maximum effect observed on day 7 post stress [0.32 ± 0.08; p = 0.007]) compared to control littermates. CONCLUSION: These data demonstrate that prolactin plays a female-specific role in stress-induced behavioral responses in this preclinical migraine model through activation of Prlr on sensory neurons. They also support a role for prolactin in migraine mechanisms in females and suggest that modulation of prolactin signaling may be an effective therapeutic strategy in some cases.

Characteristics and natural disease history of persistent idiopathic facial pain, trigeminal neuralgia, and neuropathic facial pain.

OBJECTIVE: This study aimed to characterize key features, and to assess the clinical development of common nondental facial pain syndromes such as persistent idiopathic facial pain (PIFP), trigeminal neuralgia (TN), and neuropathic facial pain (NEUROP). METHODS: This is a longitudinal study in which prospective questionnaire data of patients presenting to a specialized outpatient clinic were collected from 2009 to 2019. A telephone interview was conducted with the same patients in 2020 to assess the natural disease history. RESULTS: n = 411 data sets of patients with chronic facial pain were compiled. Among these were n = 150 patients with PIFP, n = 111 patients with TN, and n = 86 patients with NEUROP. Guideline therapy had not been initiated in 38.7% (58/150; PIFP), 19.8% (22/111; TN), and 33.7% (29/86; NEUROP) patients. Of the patients with PIFP, 99.3% (149/150) had primarily consulted a dentist due to their pain syndrome. The additional telephone interview was completed by 236 out of the 411 patients (57.4%). Dental interventions in healthy teeth had been performed with the intention to treat the pain in many patients (78/94 [83.0%] PIFP; 34/62 [54.8%] TN; 19/43 [44.2%] NEUROP), including dental extractions. 11.3% (7/43) of the patients with TN had never profited from any therapy. In contrast, 29.8% (28/94) of the patients with PIFP had never profited from any therapy. Furthermore, the primary pharmaceutical therapy options suggested by national guidelines were, depending on the substance class, only considered to be effective by 13.8% (13/94; antidepressants) and 14.9% (14/94; anticonvulsants) of the patients with PIFP. CONCLUSIONS: Facial pain syndromes pose a considerable disease burden. Although treatment of TN seems to be effective in most patients, patients with PIFP and NEUROP report poor effectiveness even when following guideline therapy suggestions. In addition, unwarranted dental interventions are common in facial pain syndromes.

Internalizing problems are associated with oral health-related quality of life in early childhood: Outcomes from an Asian multi-ethnic prospective birth cohort.

Oral health status ideally warrants for a holistic biopsychosocial approach to health and wellness. Little is known about the impact of behavioral problems on oral health-related quality of life (OHRQoL) in children due to the paucity of studies in early childhood, particularly in Asian multi-ethnic populations. This study evaluated the relationship between early child's socioemotional factors and OHRQoL, as well as its association with orofacial pain (OFP) and early childhood caries (ECC) in the Asian GUSTO birth cohort. Mother-child dyads were postnatally assessed at 3 time points. The Child Behavior Checklist (CBCL) was used to assess the child's socioemotional and behavioral problems at age 4-4.5 years together with other validated questionnaires to evaluate maternal anxiety and depression. ECC detection was performed at age 5, and OHRQoL (primary) and OFP (secondary) outcomes were assessed at age 6 from a total of 555 mother-child dyads. After a univariate regression analysis was performed to identify potential predictors and confounders, a multivariate regression model was run with predisposing factors (CBCL internalization and externalization problems, OFP, ECC) and adjusted for confounders (maternal psychosocial states, maternal education) to determine associations with OHRQoL. Results showed an association between CBCL internalization scores and poorer OHRQoL (RR = 1.03, p = 0.033, 95% CI 1.01 to 1.05), although the limited risk ratio may not have a practical applicability in psychosocially healthy children, alike the majority of those evaluated in this cohort. The average OHRQoL overall score among children with OFP was 2.39 times more than those without OFP (OR = 2.39, p < 0.001, 95% CI 2.00 to 2.86). Thus, in early childhood, OFP, and to lesser extent internalizing behaviors, may negatively impact OHRQoL. This study therefore highlights the complex relationship between OHRQoL and its predisposing socioemotional and somatic pain factors, and demands further investigations in clinically relevant populations.

Pain sensitivity increases with sleep disturbance under predictable chronic mild stress in mice.

Even though it has been well documented that stress can lead to the development of sleep disorders and the intensification of pain, their relationships have not been fully understood. The present study was aimed at investigating the effects of predictable chronic mild stress (PCMS) on sleep-wake states and pain threshold, using the PCMS rearing conditions of mesh wire (MW) and water (W) for 21 days. Exposure to PCMS decreased the amount of non-rapid eye movement (NREM) sleep during the dark phase. Moreover, the chronicity of PCMS decreased slow-wave activity (SWA) during NREM sleep in the MW and W groups in both the light and dark phases. Mechanical and aversively hot thermal hyperalgesia were more intensified in the PCMS groups than the control. Higher plasma corticosterone levels were seen in mice subjected to PCMS, whereas TNF-α expression was found higher in the hypothalamus in the W and the trigeminal ganglion in the MW group. The W group had higher expression levels of IL-6 in the thalamus as well. The PCMS paradigm decreased SWA and may have intensified mechanical and thermal hyperalgesia. The current study also suggests that rearing under PCMS may cause impaired sleep quality and heightened pain sensation to painful mechanical and aversively hot thermal stimuli.

Cannabidiol has therapeutic potential for myofascial pain in female and male parkinsonian rats.

The musculoskeletal orofacial pain is a complex symptom of Parkinson's disease (PD) resulting in stomatognathic system dysfunctions aggravated by the disease rigidity and postural instability. We tested the effect of cannabidiol (CBD), a non-psychotomimetic constituent of Cannabis sativa, in PD-related myofascial pain. Wistar adult female and male rats orofacial allodynic and hyperalgesic responses were tested by Von Frey and formalin tests, before and 21 days past 6-OHDA lesion. Algesic response was tested after masseter muscle injection of CBD (10, 50, 100 µg in 10 µL) or vehicle. Males compared to females in all estrous cycles' phases presented reduced orofacial allodynia and hyperalgesia. According to the estrous cycle's phases, females presented distinct orofacial nociceptive responses, being the estrus phase well-chosen for nociceptive analysis after 6-OHDA lesion (phase with fewer hormone alterations and adequate length). Dopaminergic neuron lesion decreased mechanical and inflammatory nociceptive thresholds in females and males in a higher proportion in females. CBD local treatment reduced the increased orofacial allodynia and hyperalgesia, in males and females. The female rats were more sensitive to CBD effect considering allodynia, responding to the lowest dose. Although females and males respond to the effect of three doses of CBD in the formalin test, males showed a superior reduction in the hyperalgesic response. These results indicate that hemiparkinsonian female in the estrus phase and male answer differently to the different doses of CBD therapy and nociceptive tests. CBD therapy is effective for parkinsonism-induced orofacial nociception.

Chronic Orofacial Pain: Models, Mechanisms, and Genetic and Related Environmental Influences.

Chronic orofacial pain conditions can be particularly difficult to diagnose and treat because of their complexity and limited understanding of the mechanisms underlying their aetiology and pathogenesis. Furthermore, there is considerable variability between individuals in their susceptibility to risk factors predisposing them to the development and maintenance of chronic pain as well as in their expression of chronic pain features such as allodynia, hyperalgesia and extraterritorial sensory spread. The variability suggests that genetic as well as environmental factors may contribute to the development and maintenance of chronic orofacial pain. This article reviews these features of chronic orofacial pain, and outlines findings from studies in animal models of the behavioural characteristics and underlying mechanisms related to the development and maintenance of chronic orofacial pain and trigeminal neuropathic pain in particular. The review also considers the role of environmental and especially genetic factors in these models, focussing on findings of differences between animal strains in the features and underlying mechanisms of chronic pain. These findings are not only relevant to understanding underlying mechanisms and the variability between patients in the development, expression and maintenance of chronic orofacial pain, but also underscore the importance for considering the strain of the animal to model and explore chronic orofacial pain processes.

Glia and Orofacial Pain: Progress and Future Directions.

Orofacial pain is a universal predicament, afflicting millions of individuals worldwide. Research on the molecular mechanisms of orofacial pain has predominately focused on the role of neurons underlying nociception. However, aside from neural mechanisms, non-neuronal cells, such as Schwann cells and satellite ganglion cells in the peripheral nervous system, and microglia and astrocytes in the central nervous system, are important players in both peripheral and central processing of pain in the orofacial region. This review highlights recent molecular and cellular findings of the glia involvement and glia-neuron interactions in four common orofacial pain conditions such as headache, dental pulp injury, temporomandibular joint dysfunction/inflammation, and head and neck cancer. We will discuss the remaining questions and future directions on glial involvement in these four orofacial pain conditions.

Differential Activation of Colonic Afferents and Dorsal Horn Neurons Underlie Stress-Induced and Comorbid Visceral Hypersensitivity in Female Rats.

Chronic Overlapping Pain Conditions, including irritable bowel syndrome (IBS) and temporomandibular disorder (TMD), represent a group of idiopathic pain conditions that likely have peripheral and central mechanisms contributing to their pathology, but are poorly understood. These conditions are exacerbated by stress and have a female predominance. The presence of one condition predicts the presence or development of additional conditions, making this a significant pain management problem. The current study was designed to determine if the duration and magnitude of peripheral sensitization and spinal central sensitization differs between restraint stress-induced visceral hypersensitivity (SIH) and chronic comorbid pain hypersensitivity (CPH; stress during pre-existing orofacial pain). SIH in female rats, as determined by the visceromotor response, persisted at least four but resolved by seven weeks. In contrast, CPH persisted at least seven weeks. Surprisingly, colonic afferents in both SIH and CPH rats were sensitized at seven weeks. CPH rats also had referred pain through seven weeks, but locally anesthetizing the colon only attenuated the referred pain through four weeks, suggesting a transition to colonic afferent independent central sensitization. Different phenotypes of dorsal horn neurons were sensitized in the CPH rats seven weeks post stress compared to four weeks or SIH rats. The current study suggests differential processing of colonic afferent input to the lumbosacral spinal cord contributes to visceral hypersensitivity during comorbid chronic pain conditions. PERSPECTIVE: Chronic Overlapping Pain Conditions represent a unique challenge in pain management. The diverse nature of peripheral organs hinders a clear understanding of underlying mechanisms accounting for the comorbidity. This study highlights a mismatch between the condition-dependent behavior and peripheral and spinal mechanisms that contribute to visceral pain hypersensitivity.

First Bite Syndrome: What Neurologists Need to Know.

PURPOSE OF REVIEW: Though first bite syndrome is well known in surgical settings, it is not commonly included in the differential for sharp paroxysmal facial pain in the neurology literature. This paper will highlight the clinical features and relevant anatomy of first bite syndrome, with the goal of helping clinicians differentiate this from other similar facial pain disorders. RECENT FINDINGS: First bite syndrome is severe sharp or cramping pain in the parotid region occurring with the first bite of each meal and improving with subsequent bites. Pathophysiology has been attributed to imbalanced sympathetic/parasympathetic innervation of the parotid gland. This is seen most typically in the post-surgical setting following surgery in the parotid or parapharyngeal region, but neoplastic etiologies have also been reported. It is common for patients to present with concurrent great auricular neuropathy and/or Horner's syndrome. Evidence regarding treatment is limited to case reports/series, however, botulinum toxin injections and neuropathic medicines have been helpful in select cases. It is critical for clinicians to be able to differentiate first bite syndrome from other paroxysmal facial pain. To help with this, we have proposed diagnostic criteria for clinical assessment. Patients often improve gradually over time, but symptomatic treatment with botulinum toxin or neuropathic medicine may be required.

Clinical and Pain-Related Characteristics of Idiopathic First Bite Syndrome Induced by Taste in Japanese Patients without Diabetes: A Retrospective Study of Five Cases.

Objective: First bite syndrome (FBS) is a condition in which the first bite of each meal causes parotid pain. Etiologies of FBS include prior surgery of the upper cervical region and, rarely, head and neck tumors. Idiopathic FBS rarely presents in patients without a history of surgery or evidence of an underlying tumor. Idiopathic FBS may be categorized into two subtypes: that in patients with diabetes and that in patients without diabetes. Idiopathic FBS in patients without diabetes may be overlooked or misdiagnosed because the condition has been described only in a few case reports. We aimed to identify the clinical and pain-related characteristics of idiopathic FBS in patients without diabetes. Methods: We retrospectively analyzed the clinical data of five patients without diabetes who were diagnosed with idiopathic FBS in our department between January 2010 and December 2016. Results: Four of the five patients were female, and the overall median age was 52 years (range: 13-61). All patients immediately experienced parotid pain upon tasting food without chewing. Addition of an acidic solution to the ipsilateral posterior third of the tongue evoked parotid pain. The median degree of pain intensity and interference with eating due to pain was 9 (range: 3-10) and 9 (range: 5-10) on a numerical rating scale of 0-10, respectively. Idiopathic FBS was bilateral in two patients. Two patients had tenderness on mild pressure over the affected parotid region. Two patients presented with ipsilateral idiopathic Horner's syndrome. Conclusions: Our findings indicate that the characteristics of idiopathic FBS in patients without diabetes are largely consistent with those previously reported in postoperative FBS, supporting the notion that idiopathic FBS is a subtype of FBS. Thus, it is necessary to consider idiopathic FBS during the evaluation of facial pain triggered at the beginning of a meal.

The Impact of Education and Physical Therapy on Oral Behaviour in Patients with Temporomandibular Disorder: A Preliminary Study.

Patient education is important in the treatment of temporomandibular disorder (TMD), but little is known about its effect on oral behaviors. We aimed to determine the dominant oral behaviours in patients with TMD and assess the impact of education on such behaviours. Between July 2018 and April 2019, 54 patients diagnosed with TMD according to DC/TMD were recruited. They received physical therapy and were provided education on TMD and offered a list of recommendations for improving their oral behaviours. The patient education process usually lasted for 10-20 min. Of these patients, 48 were reexamined at the outpatient clinic, 3-9 months posttreatment. We recorded the Oral Behaviour Checklist (OBC) score, maximum painless mouth opening (mm), visual analogue scale (VAS) score for pain, and Jaw Functional Limitation Scale (JFLS) score pre- and posttreatment. Wilcoxon signed rank test and paired sample t-test were used for statistical analysis. Results showed that the most dominant oral behaviours included "putting pressure on the jaw" (59.3%); "chewing food on one side" (46.3%); "pressing, touching, or holding teeth together at times other than eating" (33.3%); and "eating between meals" (33.3%). Posttreatment, the patients reported a decrease in "chewing gum" (P = 0.002), "leaning with the hand on the jaw" (P = 0.013), "chewing food on one side" (P ≤ 0.001), and "eating between meals" (P = 0.007), but this change was not significant in subgroups with a follow-up interval of 9 months. We also observed a significant improvement in the maximum painless mouth opening (P ≤ 0.001), JFLS score (P ≤ 0.001), and VAS score (P ≤ 0.001) for pain, posttreatment. In conclusion, patient education can facilitate management of oral behaviours and should be targeted towards specific oral behaviours.

Patogénesis del dolor en la mucositis oral. Revisión de la literatura / Pathogenesis of pain in oral mucositis. Review of the literature

INTRODUCCIÓN: La mucositis oral es una lesión dolorosa que tiene lugar en la mucosa de la cavidad oral, normalmente su etiología se encuentra asociada a tratamientos farmacológicos en pacientes oncológicos. Se presenta como úlceras bien delimitadas cuya sintomatología dolorosa supone en ocasiones la suspensión del tratamiento oncológico o la alimentación por vía parenteral, siendo por tanto un efecto adverso importante, marcando el devenir en este tipo de terapias contra el cáncer. OBJETIVO: El objetivo del presente artículo es poner en relieve cómo se produce el dolor en esta patología que acontece en la mucosa de la cavidad oral. DISCUSIÓN: La mucositis oral se va a presentar tras una cascada de eventos biológicos que implican diferentes procesos moleculares tras el tratamiento con quimioterapia o radioterapia. El dolor en la mucositis oral puede poseer un componente inflamatorio y también un componente neuropático. En su fisiopatología, el dolor va a estar mediado por diferentes familias de receptores y factores. CONCLUSIÓN: La mucositis oral presenta un gran componente doloroso asociado, en el que cobran especial protagonismo en su aparición, las familias de los receptores y factores TRP, ET-1, TNF y ROS, entre otros. El conocimiento de la patogénesis del dolor en esta patología permitirá desarrollar terapéuticas contra el dolor en estudios futuros

INTRODUCTION: Oral mucositis is a painful lesion that occurs in the mucosa of the oral cavity. Its aetiology is usually associated with drug treatments in cancer patients. It presents as well-defined ulcers whose painful symptoms sometimes lead to the suspension of cancer treatment or parenteral nutrition. They therefore represent a significant adverse effect that marks the future in this type of cancer therapy. OBJECTIVE: The objective of this article is to highlight how pain occurs in this pathology that takes place in the mucosa of the oral cavity. DISCUSSION: Oral mucositis will occur following a cascade of biological events involving different molecular processes following treatment with chemotherapy or radiotherapy. Pain in oral mucositis may have an inflammatory component as well as a neuropathic component. In its pathophysiology, pain will be mediated by different families of receptors and factors. CONCLUSION: Oral mucositis has a large associated painful component, in which the families of TRP, ET-1, TNF and ROS receptors and factors, among others, play a major role in its appearance. Knowledge of the pathogenesis of the pain in this pathology will allow pain therapies to be developed in future studies

A neuroimaging biomarker for sustained experimental and clinical pain.

Sustained pain is a major characteristic of clinical pain disorders, but it is difficult to assess in isolation from co-occurring cognitive and emotional features in patients. In this study, we developed a functional magnetic resonance imaging signature based on whole-brain functional connectivity that tracks experimentally induced tonic pain intensity and tested its sensitivity, specificity and generalizability to clinical pain across six studies (total n = 334). The signature displayed high sensitivity and specificity to tonic pain across three independent studies of orofacial tonic pain and aversive taste. It also predicted clinical pain severity and classified patients versus controls in two independent studies of clinical low back pain. Tonic and clinical pain showed similar network-level representations, particularly in somatomotor, frontoparietal and dorsal attention networks. These patterns were distinct from representations of experimental phasic pain. This study identified a brain biomarker for sustained pain with high potential for clinical translation.

Transient Receptor Potential (TRP) Ion Channels in Orofacial Pain.

Orofacial pain, including temporomandibular joint disorders pain, trigeminal neuralgia, dental pain, and debilitating headaches, affects millions of Americans each year with significant population health impact. Despite the existence of a large body of information on the subject, the molecular underpinnings of orofacial pain remain elusive. Two decades of research has identified that transient receptor potential (TRP) ion channels play a crucial role in pathological pain. A number of TRP ion channels are clearly expressed in the trigeminal sensory system and have critical functions in the transduction and pathogenesis of orofacial pain. Although there are many similarities, the orofacial sensory system shows some distinct peripheral and central pain processing and different sensitivities from the spinal sensory system. Relative to the extensive review on TRPs in spinally-mediated pain, the summary of TRPs in trigeminally-mediated pain has not been well-documented. This review focuses on the current experimental evidence involving TRP ion channels, particularly TRPV1, TRPA1, TRPV4, and TRPM8 in orofacial pain, and discusses their possible cellular and molecular mechanisms.

The receptive field for visceral pain referred orofacially by the vagus nerves.

BACKGROUND: The nociceptive receptive field of the vagus nerves in animals includes virtually the entire thoracic, abdominal and laryngopharyngeal regions. However, the role of the vagus nerves in the transmission of visceral pain in humans, with the exception of pain from coronary artery diseases, is believed to be insignificant. AIM: The purpose of this report is to map out the clinical visceral pain receptive field of the vagus nerves relative to its nociceptive counterpart in animals. MATERIALS AND METHODS: The PubMed database and PMC were searched for case reports of patients with orofacial pain believed by the author(s) of the article to be referred from underlying non-cardiac thoracic, laryngopharyngeal or abdominal diseases. Reports of diseases for which non-neural explanations for the orofacial spread of pain were suggested were excluded. RESULTS: A total of 52 case reports of jaw pain and/or otalgia referred from laryngopharyngeal and noncardiac thoracic sources were discovered. In addition, a multicenter prospective study found that 25.8% of more than 3,000 patients with thoracic aortic dissection experienced pain in the head and neck region. In stark contrast, no case reports of orofacially referred pain from abdominal diseases were found. DISCUSSION: The results indicate that the laryngopharyngeal and thoracic portions of the vagal receptive field are capable of referring pain orofacially while the abdominal portion is not. The roles of the somatotopic organization of the trigeminal sub nucleus caudalis and neuromodulation in this referral of pain were discussed. CONCLUSION: Referred orofacial pain can lead to delayed diagnosis and poorer outcome in visceral diseases.

First Bite Syndrome: Presentation of a Patient Status-Post Right Carotid Endarterectomy.

First bite syndrome (FBS) is a sharp unilateral pain in the vicinity of the angle of the mandible after taking the first bite of a meal that presents typically after surgery in the area of the ipsilateral parapharyngeal space. It is not confirmed what the pathophysiology is that causes this pain, but the proposed mechanism is the iatrogenic damage of sympathetic fibers that extend from the superior cervical ganglion (SCG) to innervate the parotid gland. The presentation of this syndrome has been acknowledged in patients who have undergone head and neck tumor resections, but it has not been documented in the same thorough manner among vascular surgery cases in the parapharyngeal space, possibly because of a higher risk of development in other head and neck surgeries, or to under-reporting of cases. To date, only 5 cases of FBS status post carotid endarterectomy have been documented in the literature. Definitive treatment of FBS has not been established. Some studies have shown improvement with amitriptyline, and carbamazepine as well as botulinum toxin injections. We will present the case of a 75 year old male who developed first bite syndrome after a right carotid endarterectomy with efforts of raising awareness of a potential acute complication of carotid endarterectomy.

Effects of 4-Week Diacutaneous Fibrolysis on Myalgia, Mouth Opening, and Level of Functional Severity in Women With Temporomandibular Disorders: A Randomized Controlled Trial.

OBJECTIVE: The purpose of this study was to assess the effects of 4-week protocol of diacutaneous fibrolysis (DF) compared with simulated DF (sham-DF) on myalgia and mouth opening. METHODS: In a sham randomized controlled trial, 34 women with temporomandibular disorders and myofascial pain were randomly divided as intervention group (IG) and sham-DF group (SG). The IG received 4 weeks of real DF, and the SG received sham. Pain was assessed through the visual analog scale and pressure pain thresholds (PPTs) on the temporomandibular joint (TMJ), and over the temporal and masseter muscles. The Mandibular Function Impairment Questionnaire was used to classify the participants regarding to the severity of the functional limitation related to TMD. RESULTS: Pain scores decreased for both groups, but the IG showed lower values at week 4, with between-group differences. Bilateral temporal PPT showed higher values at week 4, with between-group differences. The SG had lower PPTs but the IG had higher PPTs, both compared to baseline results. The time-by-group interaction and the frequency of participants above 40 mm of mouth opening showed a significant difference for the IG over time with higher results at the 4-week assessment compared to its own baseline. Both groups showed lower MFIQ scores from baseline to 4-week assessment. There was a lower frequency of a moderate level of severity for the IG. No differences were observed for TMJ or for the masseter muscles PPT. CONCLUSION: Improvements were observed for visual analog scale scores and PPTs on temporal muscles. There was a group-by-time interaction in the IG, suggesting a possible potential use of DF for mouth opening.

Reduced activity of GAD67 expressing cells in the reticular thalamus enhance thalamic excitatory activity and varicella zoster virus associated pain.

Within the reticular thalamic nucleus neurons express gamma aminobutyric acid (GABA) and these cells project to the ventral posteromedial thalamic nucleus. When GABA activity decreases the activity of excitatory cells in the ventral posteromedial nucleus would be expected to increase. In this study, we addressed the hypothesis that attenuating GABAergic cells in the reticular thalamic nucleus increases excitatory activity in the ventral posteromedial nucleus increasing varicella zoster virus (VZV) associated pain in the orofacial region. Adeno-associated virus (AAV) was infused in the reticular thalamic nucleus of Gad1-Cre rats. This virus transduced a G inhibitory designer receptor exclusively activated by designer drugs (DREADD) gene that was Cre dependent. A dose of estradiol that was previously shown to reduce VZV pain and increase GABAergic activity was administered to castrated and ovariectomized rats. Previous studies suggest that estradiol attenuates herpes zoster pain by increasing the activity of inhibitory neurons and decreasing the activity of excitatory cells within the lateral thalamic region. The ventral posteromedial nucleus was infused with AAV containing a GCaMP6f expression construct. A glass lens was implanted for miniscope imaging. Our results show that the activity of GABA cells within the reticular thalamic region decreased with clozapine N-oxide treatment concomitant with increased calcium activity of excitatory cells in the ventral posteromedial nucleus and an increased orofacial pain response. The results suggest that estradiol attenuates herpes zoster pain by increasing the activity of inhibitory neurons within the reticular thalamus that then inhibit excitatory activity in ventral posteromedial nucleus causing a reduction in orofacial pain.