RNA sequencing of the thalamus and rostral ventral medulla in rats with chronic orofacial pain.

Diagnosing and treating chronic orofacial pain is challenging due to its complex structure and limited understanding of its causes and mechanisms. In this study, we used RNA sequencing to identify differentially expressed genes (DEGs) in the rostral ventral medulla (RVM) and thalamus of rats with persistent orofacial pain, aiming to explore its development. DEGs were functionally analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Results showed a significant association between immune response and pain in this model. Key DEG mRNA expression trends were further validated using real-time quantitative polymerase chain reaction (RT-PCR), confirming their crucial roles in chronic orofacial pain. After injecting complete Freund's adjuvant (CFA) into the bilateral temporomandibular joint cavity for 14 days, we observed 293 upregulated genes and 14 downregulated genes in the RVM, and 1086 upregulated genes and 37 downregulated genes in the thalamus. Furthermore, we identified 27 common DEGs with altered expression (upregulation) in both the thalamus and RVM, including Cd74, C3, Cxcl13, C1qb, Itgal, Fcgr2b, C5ar1, and Tlr2, which are pain-associated genes. Protein-protein interaction (PPI) analysis using Cytoscape revealed the involvement of Toll-like receptors, complement system, differentiation clusters, and antigen presentation-related proteins in the interaction between the thalamus and RVM. The results of this study show that the immune system seems to have a more significant influence on chronic orofacial pain. There may be direct or indirect influence between the thalamus and RVM, which may participate in the regulation of chronic orofacial pain.

The roles of 5-HT in orofacial pain.

OBJECTIVES: Acute and chronic orofacial pain are very common and remain a vexing health problem that has a negative effect on the quality of life. Serotonin (5-HydroxyTryptamine, 5-HT) is a kind of monoamine neurotransmitter that is involved in many physiological and pathological processes. However, its role in orofacial pain remains inconclusive. Therefore, this review aims to summarize the recent advances in understanding the effect exerted by 5-HT on the modulation of orofacial pain. SUBJECTS AND METHODS: An extensive search was conducted on PubMed and Web of Science for pertinent studies focusing on the effects of 5-HT on the modulation of orofacial pain. RESULTS: In this review, we concisely review how 5-HT mediates orofacial pain, how 5-HT is regulated and how we can translate these findings into clinical applications for the prevention and/or treatment of orofacial pain. CONCLUSIONS: 5-HT plays a key role in the modulation of orofacial pain, implying that 5-HT modulators may serve as effective treatment for orofacial pain. However, further research on the precise mechanisms underlying the modulation of orofacial pain is still warranted.

Saliva and tongue microbiota in burning mouth syndrome: An exploratory study of potential roles.

OBJECTIVES: Burning mouth syndrome (BMS) is a chronic orofacial pain disorder with unclear etiology, in which the tongue is most commonly affected. This study aims to provide implication of the possible relationship between oral microbiota and the pathogenesis of BMS. MATERIALS AND METHODS: Saliva and tongue swabs of 15 primary BMS patients and 10 healthy controls were collected and assessed by 16S rRNA gene amplicon sequencing. The microbiota compositions were compared and bioinformatic analysis was conducted. RESULTS: Differences in microbiota compositions between BMS patients and healthy controls were revealed in both saliva and tongue samples. In saliva, Streptococcus, Rothia, and Neisseria were the predominant genus at the taxonomic level in BMS patients. In tongue samples, Prevotella, Streptococcus, and Neisseria were the dominant genus at the taxonomic level in BMS patients. LEfSe analysis and linear discriminant analysis score showed that Actinobacteria were the predominant phylum in saliva, and Selenomonas were enriched in the dorsum of the tongue of BMS patients. CONCLUSIONS: This study for the first-time reported saliva and tongue microbiota profiles were distinguished from that of healthy controls, indicating a necessity for further research on the possible relationship between oral microbes and the pathogenesis of BMS.

Use of antidepressants in the treatment of chronic orofacial pain caused by temporomandibular disorders: A randomized controlled clinical trial.

BACKGROUND AND OBJECTIVE: Temporomandibular disorders (TMDs) are a common pathology, associated with pain in the facial territory and with associated psychological disorders, such as anxiety and depression. The aim of this study was to evaluate the efficacy of antidepressants in the treatment of pain associated with TMD. MATERIALS AND METHODS: Sixty four patients suffering from chronic orofacial pain, randomly distributed in 3 groups: control group treated with night splint, group treated with 10mg/day of citalopram and group treated with 25mg/day of amitriptyline. Pain intensity was assessed, randomly, by a single blinded evaluator, according to the VAS at baseline and after one, three, six and nine weeks. RESULTS: All groups showed a reduction of pain throughout the period of time evaluated, however, the group treated with amitriptyline showed the best pain reduction results 3.3±1.5, 1.5±1.4 and 0.9±1.3 at 3, 6 and 9 weeks, respectively. CONCLUSIONS: Low doses of amitriptyline appear to be a good therapeutic option in patients with TMDs suffering from chronic orofacial pain.

Temporomandibular Disorders, Bruxism and Headaches.

Temporomandibular disorders (TMDs) and headache disorders are highly prevalent in the population. TMDs can present headache symptoms as a secondary headache and, in addition, be comorbid with primary headache disorders. This overlap has significant clinical implications for which it is essential for the physician to be aware, and they should screen for the potential presence of TMDs in a headache patient. Bruxism is a parafunctional behavior also prevalent in the population which has a role in TMDs and may influence headache symptomatology, but it is still necessary to clarify this relationship.

Other Secondary Headaches: Odontogenic Pain and Other Painful Orofacial Conditions.

This article discusses extremely common odontogenic pain conditions, which may occasionally present to the neurology clinic mimicking headache, and other uncommon orofacial pain conditions, which may do the same. Typical presentations, investigative strategies, and management are discussed, as well as highlighting key diagnostic criteria and the importance of involving oral or dental specialists where diagnostic uncertainty exists.

Visual psychosocial profiling of Chinese temporomandibular disorder pain patients and correlations with somatosensory function.

BACKGROUND: Psychosocial function of Chinese temporomandibular disorders (TMD) pain patients and the correlation with somatosensory function has not been sufficiently studied. OBJECTIVE: The study aims at assessing the psychosocial function of Chinese TMD pain patients by visualisation method and evaluating the correlations with somatosensory function quantitatively. METHODS: The Symptom Checklist 90 (SCL-90) questionnaire and standardised quantitative sensory testing (QST) were administered to 70 Chinese TMD pain patients and age- and gender-matched healthy controls (HCs). Of these, 40 TMD arthralgia patients received QST before and after medication. Psychosocial and somatosensory parameters were transformed into standardised scores. Differences within groups were assessed through t tests. Correlations between psychosocial and somatosensory profiles were explored through correlation analyses with Bonferroni correction for multiple comparisons. RESULTS: 100% of the Chinese TMD pain patients exhibited psychosocial distress in contrast to HCs. Anger and hostility showed negative correlation with the thermal nonnociceptive parameter (thermal sensory limen, p =.002) and nociceptive parameters (cold pain threshold and pain pressure threshold, p<.001). Correlation analysis indicated that cold detection threshold was negatively correlated with somatization and mechanical pain sensitivity had a negative correlation with anger and hostility through medical treatment (p <.001). CONCLUSIONS: Visual psychosocial profiles provided an easy overview of psychosocial function in Chinese TMD pain patients. Anger and hostility was associated with increased thermal nonnociceptive and nociceptive sensitivity to stimuli. Psychosocial distress might be negatively associated with TMD treatment response which indicated a possible need for psychological intervention during treatment.

The Comparative Efficacy of Palmitoylethanolamide (PEA) With the Combination of Pregabalin and Nortriptyline on Post-extraction Trigeminal Neuropathy by Using Magnetic Resonance (MR) Neurography: A Randomized Clinical Trial.

Aim The aim of this randomized clinical trial is to compare the efficacy of palmitoylethanolamide (PEA) with the combination of pregabalin and nortriptyline in treating post-extraction trigeminal neuropathy using magnetic resonance neurography (MRN). Methods The present prospective, randomized controlled trial was conducted on 60 patients (20 in each group). In group I (positive control group), a combination of 75 mg of pregabalin and 10 mg of nortriptyline was administered once daily for the duration of 12 weeks. In group II, 600 mg of palmitoylethanolamide was given twice a day. In group III, a combination therapy of the abovementioned drugs was given. The efficacy of the drug was assessed by measuring pain intensity in terms of the numeric rating scale (NRS) (primary outcome) and changes (signal intensity and nerve thickness) in magnetic resonance neurography (secondary outcome) at various intervals of time. The data was collected and subjected to statistical analysis using the Statistical Package for Social Sciences (SPSS) version 25 (IBM SPSS Statistics, Armonk, NY) at the significance level of P<0.05. Results A significant decrease in post-drug mean NRS scores was observed in all three groups. In terms of reduction in the mean NRS, the combination group showed the highest reduction. Palmitoylethanolamide significantly reduces pain scores with negligible side effects. Conclusion Palmitoylethanolamide helps in the reduction of mild to moderate pain of painful post-traumatic trigeminal neuropathy (PTTN) with minimal side effects, suggesting that it may be used where the use of the conventional drug is either contraindicated or not feasible.

Craniocervical Pain, Sleep Quality, Depressive Symptoms, and Physical Activity in Healthcare Workers During COVID-19 Pandemic.

BACKGROUND: An increase in the workload and use of personal protective equipment by healthcare workers was observed during the COVID-19 pandemic. Due to the connections between craniocervical structures, symptoms such as neck pain and temporomandibular symptoms could be influenced by the use of PPE. AIMS: To assess the prevalence of craniocervical pain, sleep quality, physical activity, and depressive symptoms and relationship among craniocervical symptoms in healthcare workers before and during the COVID-19 pandemic in Brazil. DESIGN: Cross-sectional study. PARTICIPANTS: Healthcare workers. SETTINGS: An online questionnaire included a self-report of craniocervical pain intensity [orofacial pain, neck pain, and headache (Numerical Rating Scale)], sleep quality (Pittsburgh Sleep Quality Index), depressive symptoms (Patient Health Questionnaire two items) and physical activity (self-report). METHODS: The sample analysis was performed by descriptive statistics, the paired t-test was used to compare symptoms intensity before and during the pandemic. The relationship between dependent and independent samples was assessed through McNemar test, Pearson's chi-squared test, and Student's independent t-test. A value of p < .05 was adopted as statistical significance. RESULTS: Overall, 147 participants replied the questionnaires. Headache, neck pain, and orofacial pain complaints increased during the pandemic in healthcare workers (p < 0.001). Craniocervical pain was correlated with poor sleep quality, probable depression, and physical activity during the pandemic (p < 0.05). CONCLUSION: Healthcare workers self-reported more craniocervical pain during the COVID-19 pandemic compared to before the pandemic. In addition, poor sleep quality, depressive symptoms, and physical inactivity were associated with craniocervical symptoms during this period.

The Association Between Orofacial Pain and Depression: A Systematic Review.

Background: The occurrence of orofacial pain is often accompanied by comorbid conditions such as depression. Even though previous studies suggested a bidirectional correlation between orofacial pain and psychological factors, some studies still provided contradictory results. Objective: This systematic review aimed at providing scientific evidence regarding the association between orofacial pain and depression in published literature. Methods: The current study is a systematic literature review (PROSPERO registration no. CRD42023438596) that was conducted by reviewing cross-sectional studies that investigated the association between orofacial pain and depression. Article selection was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance. Articles searching was performed by using three databases, namely PubMed, ScienceDirect, and Scopus using the Boolean operator method. Article screening was carried out by applying the inclusion and exclusion criteria, as well as duplication checking, suitability checking, and compatibility checking. Reviewed articles went through the risk of bias evaluation form from the Joanna Briggs Institute (JBI). Extracted data were analyzed in a qualitative method. Results: Twelve studies that were conducted on 5557 participants were included in the final review. After all articles were analyzed, the correlation between orofacial pain and depression was revealed. Most articles revealed a positive correlation between orofacial pain and depression, and the rest showed how orofacial pain patients showed significantly higher depression scores compared to those individuals without orofacial pain. Conclusion: The results of this systematic review suggested a correlation between orofacial pain and depression with varying degrees. Incorporating potential depressive symptoms' treatment, when treating orofacial pain patients, should be part of the treatment plan.

Increase in stress contributes to impaired jaw function in juvenile idiopathic arthritis: a two-year prospective study.

BACKGROUND: Stress in patients with Juvenile Idiopathic Arthritis (JIA) has been found to be associated with orofacial pain, psychological distress, jaw dysfunction and loss of daily activities in a cross-sectional study. The aim of this study was to investigate the relations between stress and change of stress over time versus changes in orofacial pain, psychosocial factors and jaw function over a two-year period in patients with JIA. METHODS: This is a two-year prospective follow-up study involving 40 JIA patients. At baseline (2015) the median age was 12 years and at two-year follow up (2018) 14 years. The JIA patients were examined clinically and with questionnaires at baseline and follow-up with the diagnostic criteria for temporomandibular disorders (DC/TMD) and completed the same set of DC/TMD questionnaires regarding orofacial pain symptoms and psychosocial factors. RESULTS: Change in stress was associated with change in catastrophizing, psychological distress as well as limitation in general function and jaw function. CONCLUSIONS: This study emphasizes the importance of maintaining a low stress level in patients with JIA since an increase in stress level over a two-year period seems to impair jaw function as well as psychological distress and catastrophizing.

Association between oxidative stress and chronic orofacial pain and potential druggable targets: Evidence from a Mendelian randomization study.

BACKGROUND: Oxidative stress indicators affect chronic orofacial pain (COFP), but how to reduce these effects is uncertain. OBJECTIVES: 11 oxidative stress biomarkers were collected as exposures, while four forms of COFP were chosen as outcomes for Mendelian randomization (MR) study. METHODS: The effect estimates between oxidative stress and COFP were calculated using inverse variance-weighted MR (IVW-MR). Then, functional mapping and annotation (FUMA) was utilized in order to carry out SNP-based functional enrichment analyses. In addition, the IVW-MR method was applied to combine effect estimates when using genetic variants associated with oxidative stress biomarkers as an instrument for exploring potential druggable targets. RESULTS: The results indicated that oxidative stress biomarkers (causal OR of uric acid (UA), 0.998 for myofascial pain, 95% CI 0.996-1.000, p < .05; and OR of glutathione transferase (GST), 1.002 for dentoalveolar pain, 95% CI 1.000-1.003, p < .05) were significantly linked with the probability of COFP. Functional analysis also demonstrated that UA and myofascial pain genes were prominent in nitrogen and uracil metabolism, while GST and dentoalveolar pain genes were enriched in glutathione metabolism. Also, the study provided evidence that solute carrier family 2 member 9 (SLC2A9) and glutathione S-transferase alpha 2 (GSTA2) cause discomfort in the myofascial pain (OR = 1.003, 95% CI 1.000-1.006; p < .05) and dentoalveolar region (OR = 1.001, 95% CI 1.000-1.002; p < .05), respectively. CONCLUSIONS: In conclusion, this MR study indicates that genetically predicted myofascial pain was significantly associated with decreased UA and dentoalveolar pain was significantly associated with increased GST level. SLC2A9 inhibitor and GSTA2 inhibitor were novel chronic orofacial pain therapies and biomarkers, but clinical trials are called to examine if these oxidative biomarkers have the protective effect against orofacial pain, and further research are needed to explore the underlying mechanisms.

Anxiety, pain catastrophizing, and pain outcomes among older adults with chronic orofacial pain.

Although chronic orofacial pain (COFP) is common among older adults, the role of psychological factors in pain outcomes among this population has received limited attention. This study examined the role of anxiety and pain catastrophizing, two corelates of pain in other populations, in pain intensity and interference among 166 older adults with COFP (79% female, Mage = 68.84, SD = 5.56). Participants completed an online survey including measures of anxiety, pain catastrophizing, and pain intensity/interference. We applied mediation analyses to test indirect associations between anxiety and pain outcomes via pain catastrophizing. Results indicated that anxiety was positively associated with pain intensity and pain interference (bs = .70-1.12, ps < .05). There was also an indirect association between anxiety and pain interference through pain catastrophizing (b = .35, 95% CI [.0383, .7954]), indicating pain catastrophizing partially accounts for this relationship. Assessing and addressing anxiety and pain catastrophizing has the potential to improve treatment outcomes in this population.

Glossopharyngeal neuralgia due to vertebrobasilar dolichoectasia: a case report.

BACKGROUND: Glossopharyngeal neuralgia due to vertebrobasilar dolichoectasia is a rare form of neuropathic pain and presents with diagnostic and therapeutic challenges. CLINICAL PRESENTATION: A 67-year-old man presented with severe burning pain in the left oral cavity, with no explanatory findings during dental and ENT evaluations. TMJ examination revealed tenderness, and panoramic radiographs showed a non-contributory periapical radiolucency. MRI/MRA revealed abnormally tortuous vertebral arteries compressing the glossopharyngeal nerves and the brainstem. Topical lidocaine reduced pain, confirming glossopharyngeal neuralgia (GPN). Carbamazepine was initially ineffective, but at 200 mg pain reduced from 90 to 20 on the visual analog scale. The patient requested and underwent microvascular decompression (MVD) surgery, which eliminated his pain. CONCLUSION: When the vertebral artery compresses the glossopharyngeal nerve, the pain is more intense, attributed to its thicker vascular structure. Local anesthetic testing aids in identifying GPN. Dentists must be skilled in diagnostics and possess anatomical knowledge for accurate evaluation and referral of throat and ear pain.

Cross-Cultural Validation of the Thai Oral Health Impact Profile for Temporomandibular Disorders.

OBJECTIVES: The Oral Health Impact Profile for Temporomandibular Disorders (OHIP-TMDs) is a validated condition-specific outcome measure to help guide decision-making in the management of the condition. There is no Thai version of OHIP-TMDs, and therefore the original English version needs cross-cultural adaptation translation, and validation with a Thai population to reduce the anomalies due to language and cultural differences. This study aimed to develop the Thai-language version of OHIP-TMDs, perform a cross-cultural adaptation to Thailand, and assess its content validity, internal consistency, reliability, and construct validity. METHODS: The original English version of OHIP-TMDs was forward and backward translated into Thai language using the International Network for Orofacial Pain and Related Disorders methodology (INfORM) protocol for cross-cultural adaptation. The Content Validity Index (CVI) was performed by 5 orofacial pain (OFP) specialists to establish content validity. The OHIP-TMDs-T was then tested in 2 groups of Thai dental patients including 110 TMD patients and 110 control participants. The internal reliability and test-retest reliability (n = 30) were investigated in the TMD group using Cronbach alpha coefficient and intraclass correlation coefficient (2-way mixed effect model), respectively. The difference in OHIP-TMDs-T score between the TMD group and control group was investigated for known group validity. RESULTS: Cronbach alpha and intraclass correlation coefficients were 0.942 and 0.797, respectively. The CVI collected from the OFP specialists was 0.92. There was a statistical difference in the OHIP-TMDs-T overall score between the TMD group (95% CI, 40-46) and control group (95% CI, 2.0-3.4) (Z = 9.060, r = 1, P < .001). CONCLUSIONS: The OHIP-TMDs-T is a valid and reliable tool for evaluating the quality of life and the impact on oral health in Thai patients with TMD.

The blink reflex and its modulation - Part 2: Pathophysiology and clinical utility.

The blink reflex (BR) is integrated at the brainstem; however, it is modulated by inputs from various structures such as the striatum, globus pallidus, substantia nigra, and nucleus raphe magnus but also from afferent input from the peripheral nervous system. Therefore, it provides information about the pathophysiology of numerous peripheral and central nervous system disorders. The BR is a valuable tool for studying the integrity of the trigemino-facial system, the relevant brainstem nuclei, and circuits. At the same time, some neurophysiological techniques applying the BR may indicate abnormalities involving structures rostral to the brainstem that modulate or control the BR circuits. This is a state-of-the-art review of the clinical application of BR modulation; physiology is reviewed in part 1. In this review, we aim to present the role of the BR and techniques related to its modulation in understanding pathophysiological mechanisms of motor control and pain disorders, in which these techniques are diagnostically helpful. Furthermore, some BR techniques may have a predictive value or serve as a basis for follow-up evaluation. BR testing may benefit in the diagnosis of hemifacial spasm, dystonia, functional movement disorders, migraine, orofacial pain, and psychiatric disorders. Although the abnormalities in the integrity of the BR pathway itself may provide information about trigeminal or facial nerve disorders, alterations in BR excitability are found in several disease conditions. BR excitability studies are suitable for understanding the common pathophysiological mechanisms behind various clinical entities, elucidating alterations in top-down inhibitory systems, and allowing for follow-up and quantitation of many neurological syndromes.

Sociodemographic Profile: A Forgotten Factor in Temporomandibular Disorders? A Scoping Review.

The literature on Temporomandibular Disorders (TMD) incidence commonly reports sociodemographic factors such as gender and age. However, the role and prevalence of other sociodemographic factors in TMD are not well defined. Therefore, this scoping review aimed to report the prevalence of sociodemographic factors in TMD patients. A systematic search was conducted in the PubMed and Web of Science databases to identify clinical trials in adult populations, using the Research Diagnostic Criteria for TMD (RDC/TMD) or the Diagnostic Criteria for TMD (DC/TMD) and reporting sociodemographic data in TMD patients. Twenty-seven studies meeting the criteria were included in this review. The most commonly reported sociodemographic factors assessed in the included studies were age, race, education, job, income, and marital status. TMD prevalence was observed to be higher among younger and divorced individuals among the included studies. However, conflicting results were found for education level, and employment was not considered a risk factor for TMD. Although this review has methodological limitations, it suggests an association between TMD incidence and certain sociodemographic factors; nevertheless, further studies are needed to establish this relationship more conclusively.

Impact of working and learning from home during the COVID-19 pandemic on the head, the neck and orofacial health: A cross-sectional pilot study.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, about 81% of the world's population moved their workplace to a home office. OBJECTIVES: The main objective of this cross-sectional pilot study was to determine the impact of working and/or learning from home during the COVID-19 pandemic on the head, the neck and orofacial health in university students, faculty and staff. MATERIAL AND METHODS: Participants from 4 universities were recruited for an online survey. The survey included 33 questions related to demographics, health issues before and during the lockdown, work/study from home, and the awareness of the health effects of the lockdown. Descriptive statistics and single logistic regression analysis were employed. RESULTS: A total of 96 subjects aged 26 ±10.5 years participated in the study. Of these, 60% did not consider their home workstation to be adequate. The development of new symptoms or the worsening of the pre-existing symptoms was observed in 67%, 24%, 59%, and 37% of the participants with regard to neck pain, temporomandibular joint (TMJ)-related issues, headaches, and parafunctional oral habits, respectively. In addition, 87% of the respondents reported that their oral habits were aggravated by neck pain and a bad posture. As compared to the faculty and the staff, the students were more likely to experience headaches or the exacerbation of the pre-existing headaches during the pandemic. In the survey, 91% of the participants reported an increased awareness of the impact of the lockdown on their head and neck, and orofacial health. CONCLUSIONS: The present study helps understand the self-perceived effects of working and/or learning from home during the COVID-19 pandemic, and may facilitate implementing the appropriate models of treatment of the craniocervical-mandibular region during a pandemic.

Role of neuropeptides in orofacial pain: A literature review.

BACKGROUND: Neuropeptides play a critical role in regulating pain and inflammation. Despite accumulating evidence has further uncovered the novel functions and mechanisms of different neuropeptides in orofacial pain sensation and transmission, there is deficient systematic description of neuropeptides' pain modulation in the orofacial region, especially in the trigeminal system. OBJECTIVES: The present review aims to summarise several key neuropeptides and gain a better understanding of their major regulatory roles in orofacial inflammation and pain. METHODS: We review and summarise current studies related to calcitonin gene-related peptide (CGRP), substance P (SP), opioid peptide (OP), galanin (GAL) and other neuropeptides' functions and mechanisms as well as promising targets for orofacial pain control. RESULTS: A number of neuropeptides are clearly expressed in the trigeminal sensory system and have critical functions in the transduction and pathogenesis of orofacial pain. The functions, possible cellular and molecular mechanisms have been introduced and discussed. Neuropeptides and their agonists or antagonists which are widely studied to be potential treatment options of orofacial pain has been evaluated. CONCLUSIONS: Various neuropeptides play important but distinct (pro-nociceptive or analgesic) roles in orofacial pain with different mechanisms. In summary, CGRP, SP, NPY, NKA, HK-1, VIP mainly play proinflammatory and pro-nociceptive effects while OP, GAL, OXT, OrxA mainly have inhibitory effects on orofacial pain.

Effect of chronic intermittent hypoxia on ocular and intraoral mechanical allodynia mediated via the calcitonin gene-related peptide in a rat.

STUDY OBJECTIVES: Obstructive sleep apnea, a significant hypoxic condition, may exacerbate several orofacial pain conditions. The study aims to define the involvement of calcitonin gene-related peptide (CGRP) in peripheral and central sensitization and in evoking orofacial mechanical allodynia under chronic intermittent hypoxia (CIH). METHODS: Male rats were exposed to CIH. Orofacial mechanical allodynia was assessed using the eyeblink test and the two-bottle preference drinking test. The CGRP-immunoreactive neurons in the trigeminal ganglion (TG), CGRP-positive primary afferents projecting to laminae I-II of the trigeminal spinal subnucleus caudalis (Vc), and neural responses in the second-order neurons of the Vc were determined by immunohistochemistry. CGRP receptor antagonist was administrated in the TG. RESULTS: CIH-induced ocular and intraoral mechanical allodynia. CGRP-immunoreactive neurons and activated satellite glial cells (SGCs) were significantly increased in the TG and the number of cFos-immunoreactive cells in laminae I-II of the Vc were significantly higher in CIH rats compared to normoxic rats. Local administration of the CGRP receptor antagonist in the TG of CIH rats attenuated orofacial mechanical allodynia; the number of CGRP-immunoreactive neurons and activated SGCs in the TG, and the density of CGRP-positive primary afferent terminals and the number of cFos-immunoreactive cells in laminae I-II of the Vc were significantly lower compared to vehicle-administrated CIH rats. CONCLUSIONS: An increase in CGRP in the TG induced by CIH, as well as orofacial mechanical allodynia and central sensitization of second-order neurons in the Vc, supported the notion that CGRP plays a critical role in CIH-induced orofacial mechanical allodynia.