BACKGROUND: Inhibition of astrocytic energy metabolism alleviates neuropathic pain.
OBJECTIVE: To explore whether astrocyte-neuron lactate shuttle (ANLS) played any role in neuropathic orofacial pain.
METHODS: Rats with partial transection of the right infraorbital nerve (p-IONX) or sham operation were intrathecally injected with acetazolamide (a carbonic anhydrase inhibitor), bithionol (a soluble adenylyl cyclase inhibitor), α-cyano-4-hydroxycinnamic acid [α-CHCA, a monocarboxylate transporter (MCT) inhibitor] or vehicle once a day from postoperative day 1-14. The facial mechanical thresholds were tested on preoperative day 1 and 2 and postoperative days 1, 3, 5, 7, 10 and 14, expression of glucose transporters (GLUTs) and MCTs in the trigeminal subnucleus caudalis (Vc) were examined on the postoperative day 3 and neuronal activities in the Vc were examined in the p-IONX rats on postoperative days 3-5.
RESULTS: Compared with the sham group, the mechanical thresholds in the p-IONX group were significantly reduced at postoperative days 1-7, and the number of astrocytes expressing GLUT1 and MCT1/4, and neurons expressing MCT2 was significantly increased on postoperative day 3. In the p-IONX groups, neurons in the Vc were sensitised, and acetazolamide, bithionol and α-CHCA reversed the central sensitisation, significantly increased the mechanical thresholds at postoperative days 1-7 and decreased the number of astrocytes expressing GLUT1 and MCT1/4, and neurons expressing MCT2 at postoperative day 3 compared with those in the vehicle-treated rats.
CONCLUSIONS: Inhibition of ANLS alleviates p-IONX-related neuronal, behavioural and immunohistochemical changes, which suggests that ANLS plays an important role in trigeminal neuropathic pain.

BACKGROUND: COVID-19 infection shows variant symptoms apart from respiratory symptoms, including the orofacial pain. We aim to research the morbidity, characteristics and potential risk factors of orofacial pain associated with COVID-19 pandemic in China from December 2022 to early 2023.
METHODS: A cross-sectional survey was conducted in Fujian Province, China. The demographic and characteristic data of the subjects were collected and analysed.
RESULTS: A total of 1526 subjects responded to the survey. The morbidity of orofacial pain increased significantly before and after COVID-19 infection. (42.26% vs. 46.52%, P < .001) A total of 217 (14.22%) subjects with orofacial pain before COVID-19 infection reported the phenomenon of \"COVID-19 infection with orofacial pain\" (CIOP). Univariate and multivariate logistic regression showed that male (OR = 1.761, P < .001) and other symptoms of COVID-19 (OR = 1.494, P < .001) may be the risk factors for the aggravation of CIOP, while the time of first infection (OR = 0.580, P = .004) and preference for drinking tea or coffee (OR = 0.610, P = .003) may be the protective factors for the aggravation of CIOP. While, the subjects who did not concern about the spread of COVID-19 in oral treatment (OR = 0.639, P = .001), female (OR = 0.749, P = .03), education level (OR = 1.687, P < .001) and income level (OR = 1.796, P < .001), higher PSS-10 score (OR = 1.076, P < .001), and more drugs taken for infection (OR = 1.330, P < .001) were more willing to seek medical treatment.
CONCLUSIONS: The morbidity of orofacial pain appears to have increased significantly due to the COVID-19 epidemic; a number of factors can influence the CIOP including gender, infection period, and beverage preference\' psychological factors, gender, education and income level can also influence the intent to seek a dentist.

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.

OBJECTIVE: 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.
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.

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.
OBJECTIVE: 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.

This study aimed to translate and adapt the Brief Pain Inventory-Facial (BPI-F) into Chinese, proposing a validated Chinese version for clinical application.
To evaluate the applicability of Chinese BPI-F, this study included two groups: clinical sample (406 patients with OFP) and non-clinical sample (514 college students without OFP medical history). Content validity was improved through patient interviews. Cronbach\'s α was used to evaluate the reliability of BPI-F in both groups. The best-fit factor structure was tested on clinical sample via exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Convergent and discriminant validity of BPI-F was evaluated by Spearman\'s coefficient. Serial CFA was used to assess measurement invariance between the two groups.
Content validity and reliability of BPI-F were verified. EFA results support a two-factor structure, interference with general activities (1-7 items) and face-specific pain interference (8-14 items). CFA results demonstrated this two-factor structure is appropriate for different populations. Spearman results showed that BPI-F had good convergent and discriminant validity. Full measurement invariance is observed across the two groups.
The Chinese BPI-F, with two-factor structure (interference with general / orofacial functions), enables accurate assessment of functional interference caused by OFP. BPI-F has the same significance in different clinical populations, which expands its application.
This manuscript proposed the Chinese version of the BPI-F and examined its psychometric characteristics for the first time. This validated scale provides a favorable instrument for aiding individual diagnosis and treatment for OFP patients in China.

To evaluate the correlation between obstructive sleep apnea (OSA) and temporomandibular joint (TMJ) morphology, tooth wear condition, orofacial pain through a follow-up program.
Seventy one OSA patients were divided into three groups according to their (apnea hypopnea index) AHI: mild group (n = 23), moderate group (n = 24), and severe group (n = 24). All patients had OSA therapies around six months after confirm the diagnosis of OSA. The tooth wear score and orofacial pain condition of all patients were recorded via clinical examination. Cone beam computed tomography (CBCT) images were also taken when confirm the diagnosis of OSA (T0), 6 months after the diagnosis (T1), and 6 months after the OSA treatment (T2). Parameters indicating the condylar morphology and joint space were evaluated. The differences of clinical symptoms and TMJ conditions among T0, T1 and T2 time point were detected in the three groups respectively. The changes in T1-T0 and T2-T1 of all descriptions among three groups were also compared. The correlations between AHI and clinical symptoms were detected with Spearman correlation analysis.
In mild group, there was no difference in all clinical symptoms and TMJ morphology among the three time points. Both in moderate and severe group, the condylar volume, superficial area, wear score, visual analogue scales (VAS), and R value (indicating condyle position) displayed significant differences among the three time points (P < 0.05). From T0 to T1, mild group displayed fewer decreases in the condylar volume and superficial area and fewer increases in wear score than that in moderate and severe group (P < 0.05). From T1 to T2, there was a greatest reduction in severe group for R value, and significant difference in the description of VAS and R value were found among the three groups. AHI was negatively correlated condylar volume and condylar superficial area, and was positively correlated with tooth wear score and VAS (P < 0.05).
Moderate to severe OSA will aggravate orofacial pain and tooth wear, affect TMJ volume and superficial area, even change the location of condyles. Appropriate OSA therapies may be effective ways to alleviate these adverse effects in long-term.

Temporomandibular joint osteoarthritis (TMJOA) is a common inflammatory disease that can cause pain, cartilage degradation, and subchondral bone loss. However, the key regulatory factors and new targets for the treatment of TMJOA have yet to be determined. Long noncoding RNAs (lncRNAs) have shown remarkable potential in regulating tissue homeostasis and disease development. The long intergenic RNA-erythroid prosurvival (lincRNA-EPS) is reported to be an effective inhibitor of inflammation, but its role in TMJOA is unexplored. Here, we found that lincRNA-EPS is downregulated and negatively correlated with inflammatory factors in the condyles of TMJOA mice. LincRNA-EPS knockout aggravated inflammation and tissue destruction after TMJOA modeling. The in vitro studies confirmed that loss of lincRNA-EPS facilitated inflammatory factor expression in condylar chondrocytes, while recovered expression of lincRNA-EPS showed anti-inflammatory effects. Mechanistically, RNA sequencing revealed that the inflammatory response pathway nuclear factor-kappa B (NF-κB) was mostly affected by lincRNA-EPS deficiency. Moreover, lincRNA-EPS was proved to effectively bind to serine/arginine-rich splicing factor 3 (SRSF3) and inhibit its function in pyruvate kinase isoform M2 (PKM2) formation, thus restraining the PKM2/NF-κB pathway and the expression of inflammatory factors. In addition, local injection of the lincRNA-EPS overexpression lentivirus significantly alleviated inflammation, cartilage degradation, and subchondral bone loss in TMJOA mice. Overall, lincRNA-EPS regulated the inflammatory process of condylar chondrocytes by binding to SRSF3 and showed translational application potential in the treatment of TMJOA.

Orofacial pain (OFP) is a highly prevalent disorder in mainland China that predisposes to an associated physical and psychological disability. There is lack of a good properties mainland Chinese version of instrument to examine OFP. This study aims to cross-cultural adaptation and evaluate psychometrics properties of the Manchester Orofacial Pain Disability Scale (MOPDS) in mainland Chinese Mandarin context.
Translation and cross-cultural adaption of the mainland Chinese version MOPDS were conducted following accepted guidelines of self-report measures. Chinese college students (N = 1039) completed the mainland Chinese version of the MOPDS for item analysis, reliability and validity tests, and measurement invariance analysis, and after a one-month interval, around 10% of the sample (n = 110) were invited to retest. To conduct the CFA and measurement invariance analysis, Mplus 8.4 was used. IBM SPSS Statistics 26 software were used for all additional studies.
We found that the mainland Chinese version of MOPDS contains 25 items, divided into two categories: physical disability and psychological disability. The scale demonstrated excellent internal reliability, test-retest reliability, and validity. The measurement invariance results proved that the scale could be applied to people of different gender, age, and health consultation status.
The results demonstrated the mainland Chinese version of MOPDS has good psychometric properties and can be used to measure the level of physical and psychological disability of Chinese OFP peoples.

BACKGROUND: Joint effusion is often noticed in magnetic resonance image (MRI) and its diagnostic value for arthralgia of the temporomandibular joint (TMJ) remains obscure.
OBJECTIVE: To develop a method for quantitatively evaluating the joint effusion revealed in MRI and its diagnostic value for arthralgia of the TMJ.
METHODS: Two-hundreds and twenty-eight TMJs, 101 with arthralgia (Group P) and 105 without (Group NP) from 103 patients, and 22 TMJs (Group CON) from 11 asymptomatic volunteers were examined by using MRI. The effusion volume was measured after constructing a three-dimensional structure of the joint effusion revealed in MRI by using the ITK-SNAP software. The diagnostic capabilities of the effusion volume on arthralgia were evaluated with receiver operating characteristic (ROC) curve analysis.
RESULTS: Totally 146 joints showed MRI signs of joint effusion, including nine joints from Group CON. However, the medium volume was greater in Group P (66.65 mm3 ), but was much similar in Group CON (18.33 mm3 ) to Group NP (27.12 mm3 ). The effusion volume larger than 38.20 mm3 was validated to discriminate Group P from Group NP. The AUC value was 0.801 (95% CI 0.728 to 0.874), with a sensitivity of 75% and specificity of 78.9%. The median volume of the joint effusion was larger in those with than without bone marrow oedema, osteoarthritis, Type-III disc configurations, disc displacement and higher signal intensity of the retrodiscal tissue (all, p < .05).
CONCLUSIONS: The present method for evaluate joint effusion volume well discriminated painful TMJs from non-pain ones.