Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

Article Types

Countries / Regions

Search Results (74)

Search Parameters:
Keywords = chronic orofacial pain

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
16 pages, 1042 KB  
Review
Injectable Therapies for Orofacial Myofascial Pain: A Rapid Review of Randomized Controlled Trials
by Karolina Grzybowska-Kowalczyk, Izabella Chyży, Kamila Chęcińska, Wojciech Macek, Maja Kosińska, Maciej Chęciński, Amelia Hoppe, Julia Kasprzycka, Oliwia Jagiełło, Tomasz Horodniczy, Zuzanna Baniak and Maciej Sikora
J. Clin. Med. 2026, 15(13), 5143; https://doi.org/10.3390/jcm15135143 - 1 Jul 2026
Viewed by 183
Abstract
Background/Objectives: Orofacial myofascial pain (MFP) is one of the leading causes of chronic orofacial pain, often resulting in functional limitations and a compromised quality of life. Intramuscular injection therapies appear to be a promising alternative for patients resistant to conservative treatment. The objective [...] Read more.
Background/Objectives: Orofacial myofascial pain (MFP) is one of the leading causes of chronic orofacial pain, often resulting in functional limitations and a compromised quality of life. Intramuscular injection therapies appear to be a promising alternative for patients resistant to conservative treatment. The objective of this rapid review was to synthesize evidence from randomized controlled trials evaluating intramuscular injectable therapies for orofacial myofascial pain. Specifically, the review aimed to compare the clinical effects of different injectable agents on pain intensity, mandibular function, and patient-reported outcomes, and to identify methodological limitations and research gaps within the current evidence base. Methods: A comprehensive search across five databases (ACM, BASE, Cochrane, PubMed, and Scopus) was conducted on March 15, 2026. Randomized controlled trials (RCTs) published between 2022 and 2026 that investigated the use of active injectable agents into the masticatory muscles for clinically diagnosed myofascial pain syndrome were included. Data regarding post-interventional pain intensity, masticatory function, mandibular range of motion, and safety were extracted to compare therapeutic efficacy across interventions. Results: A total of five RCTs met the inclusion criteria. Eligible studies evaluated intramuscular injections of botulinum toxin A, platelet-rich plasma (PRP), magnesium sulfate, and lidocaine, with sample sizes ranging from 30 to 180 participants. Across all interventions, consistent reductions in pain intensity and enhancements in masticatory function were observed. Furthermore, no major adverse events were reported. Conclusions: Intramuscular injectable therapies represent an emerging approach for reducing orofacial myofascial pain, particularly as a treatment for patients with persistent symptoms. Full article
(This article belongs to the Special Issue Current Clinical Research in Oral Maxillofacial Surgery)
Show Figures

Graphical abstract

22 pages, 1857 KB  
Review
Burning Mouth Syndrome, the Oral Microbiome, and Lactic Acid Bacteria: A Comprehensive Review of Clinical Features, Microbial Dysbiosis, and Probiotic Therapeutic Potential
by Young Ju Jin, Jeong-Ah Yoon and Yoon-Jong Ryu
Microorganisms 2026, 14(7), 1420; https://doi.org/10.3390/microorganisms14071420 - 29 Jun 2026
Viewed by 428
Abstract
Background: Burning mouth syndrome (BMS) is a chronic orofacial pain disorder characterized by persistent intraoral burning recurring daily for at least 2 h over more than 3 months, without explanatory mucosal or laboratory findings. It affects 1.7–7.7% of the population, predominantly perimenopausal [...] Read more.
Background: Burning mouth syndrome (BMS) is a chronic orofacial pain disorder characterized by persistent intraoral burning recurring daily for at least 2 h over more than 3 months, without explanatory mucosal or laboratory findings. It affects 1.7–7.7% of the population, predominantly perimenopausal and postmenopausal women, and conventional pharmacotherapy offers only partial relief. Aim: This narrative review examines the associative and mechanistic evidence linking the oral microbiome to BMS and evaluates the rationale for lactic acid bacteria (LAB) as a candidate therapeutic strategy. Methods: PubMed/MEDLINE, Scopus, and Web of Science were searched for English-language literature on BMS, the oral microbiome, and probiotics, supplemented by mechanistic data from related conditions. Results: BMS patients may exhibit a compositionally distinct salivary microbiome, with reduced alpha diversity in psychiatric-comorbid subsets, though findings are heterogeneous. LAB, particularly Lacticaseibacillus paracasei, show antimicrobial and immunomodulatory properties relevant to oral homeostasis, but direct clinical evidence in BMS remains scarce and largely preclinical. Conclusions: Current evidence is predominantly cross-sectional and associative; the oral dysbiosis–BMS link and the therapeutic potential of LAB should be regarded as hypothesis-generating, warranting biomarker-anchored, strain-specific randomized trials. Full article
(This article belongs to the Section Medical Microbiology)
Show Figures

Figure 1

13 pages, 422 KB  
Article
Oral Health-Related Quality of Life and Maxillary Function in Wind Instrument Musicians: A Cross-Sectional Survey
by António Pereira Costa and José Frias-Bulhosa
BioMed 2026, 6(2), 14; https://doi.org/10.3390/biomed6020014 - 12 Jun 2026
Viewed by 297
Abstract
Background/Objectives: The performance of musical wind instruments imposes significant neuromuscular and biomechanical demands on the stomatognathic system. Depending on the mouthpiece type, wind instruments are divided into four classes, which may have distinct impacts on the instrumentalists’ quality of life. This study aimed [...] Read more.
Background/Objectives: The performance of musical wind instruments imposes significant neuromuscular and biomechanical demands on the stomatognathic system. Depending on the mouthpiece type, wind instruments are divided into four classes, which may have distinct impacts on the instrumentalists’ quality of life. This study aimed to evaluate musicians’ self-perception regarding the impact caused by wind instruments practice on oral health-related quality of life (OHRQoL), jaw functional limitations, and chronic pain. Methods: A cross-sectional observational study was conducted among 71 wind instrumentalists (52% female; mean age 24.16 years; mean practice history of 12.8 years) using the Oral Health Impact Profile-14 (OHIP-14), the Jaw Functional Limitation Scale (JFLS), and the Graded Chronic Pain Scale (GCPS). Data were analyzed using the Statistical Package for the Social Sciences (SPSS), with statistical significance set at p < 0.05. Results: Musicians in Class 1 (clarinet/saxophone) and Class 4 (transverse flute) reported the worst OHRQoL and chronic pain scores. Orofacial pain in the jaw, temple, or ear was reported by 66% of the participants. Joint sounds (36%) and closed jaw locking (26%) showed a significant association with female gender; however, this relationship is highly confounded by the strong female clustering in Class 4 (85%) and Class 1 (63%). Behavioral and practice habits significantly influenced outcomes: higher daily study duration (mean 170.31 min), the absence of relaxation exercises, and a willingness to endure physical discomfort for technical progress (73.2%) were significantly associated with lower quality of life and greater functional limitations (mastication and mobility). Performance anxiety, warm-up exercises, and practice intensity peaks showed no significant relationships with OHRQoL. Conclusions: Wind instrument practice severely impacts jaw function and musicians’ well-being. These findings underscore the need for interdisciplinary preventive interventions, including targeted ergonomic training, structured rest protocols, and jaw relaxation exercises, alongside oral public health initiatives that recognize wind musicians as an occupationally vulnerable group. Full article
Show Figures

Figure 1

15 pages, 558 KB  
Article
Association Between Clinical Signs and CBCT-Confirmed TMJ Involvement in Juvenile Idiopathic Arthritis: The Diagnostic Value of Facial Asymmetry and Mandibular Mobility
by Tamara Pawlaczyk-Kamieńska and Tomasz Kulczyk
Biomedicines 2026, 14(5), 1164; https://doi.org/10.3390/biomedicines14051164 - 21 May 2026
Viewed by 548
Abstract
Juvenile idiopathic arthritis (JIA) is the most common systemic chronic inflammatory connective tissue disease in children, characterized by joint inflammation lasting at least six months. Temporomandibular joint (TMJ) involvement can occur in conjunction with other joints and may often be asymptomatic in its [...] Read more.
Juvenile idiopathic arthritis (JIA) is the most common systemic chronic inflammatory connective tissue disease in children, characterized by joint inflammation lasting at least six months. Temporomandibular joint (TMJ) involvement can occur in conjunction with other joints and may often be asymptomatic in its early stages. Objective: This study aims to evaluate the relationship between clinical symptoms of the stomatognathic system and radiologically confirmed cone beam computed tomography (CBCT)-detected structural TMJ changes in children with JIA. The research hypothesis posits that specific clinical symptoms are more prevalent in patients with CBCT-confirmed structural TMJ changes. Methods: A cohort of children diagnosed with JIA was examined. Clinical symptoms, including facial asymmetry, limited mandibular movement, and joint and masticatory muscle pain upon palpation, were assessed. CBCT imaging was performed to assess osseous TMJ structural changes. Results: The frequency of orofacial clinical symptoms was assessed and compared between patients with and without radiological evidence of TMJ involvement. Children with CBCT-confirmed TMJ changes demonstrated significantly higher rates of facial asymmetry, reduced maximum mouth opening, mandibular deviation during opening, and limitations in lateral or protrusive movements compared with those without TMJ involvement. Pain-related symptoms (TMJ pain, muscle tenderness, and pain during movement) and joint sounds occurred at similar frequencies in both groups. Conclusions: Facial asymmetry, mandibular deviation during opening and reduced mandibular mobility are the clinical signs most strongly associated with structural TMJ involvement in JIA and should prompt targeted imaging. Pain-related symptoms show limited diagnostic value, highlighting the need for focused clinical assessment and future studies integrating CBCT and MRI to refine early screening protocols. Full article
Show Figures

Figure 1

14 pages, 278 KB  
Review
Burning Mouth Syndrome: Review of Current and Emerging Therapeutic Strategies
by Pierangelo Burdo, Roberta Pasqualone, Amar Ferati, Mattia Sozzi, Cristina Meuli and Giuseppe Varvara
Oral 2026, 6(2), 46; https://doi.org/10.3390/oral6020046 - 17 Apr 2026
Viewed by 2555
Abstract
Background/Objectives: Burning mouth syndrome (BMS) is a chronic idiopathic orofacial pain disorder characterized by persistent intraoral burning in the absence of detectable mucosal alterations. Diagnosis is challenging due to the lack of specific biomarkers and the need to exclude numerous systemic and local [...] Read more.
Background/Objectives: Burning mouth syndrome (BMS) is a chronic idiopathic orofacial pain disorder characterized by persistent intraoral burning in the absence of detectable mucosal alterations. Diagnosis is challenging due to the lack of specific biomarkers and the need to exclude numerous systemic and local conditions that can mimic oral burning. This literature review aims to summarize current and emerging therapeutic strategies for BMS. Methods: A structured and filtered search of PubMed, Scopus, and Web of Science identified studies evaluating pharmacological, phytotherapeutic, and non-pharmacological interventions. Results: Various antidepressants, anticonvulsants, benzodiazepines, H2 receptor antagonists, and low-dose naltrexone have demonstrated varying degrees of symptom reduction, while alpha lipoic acid (ALA) and phytomedicines such as capsaicin, Hypericum perforatum, Catuama, lycopene, crocin, and melatonin show mixed clinical benefits. Non-pharmacological approaches, including photobiomodulation (PBM), oral cryotherapy, neuromodulation techniques, and cognitive behavioral therapy, also provide meaningful symptom improvement in many patients. Conclusions: Across all modalities, therapeutic responses remain heterogeneous and generally incomplete, underscoring the absence of a universally effective treatment. Current evidence supports an individualized and multidisciplinary approach that integrates pharmacological, psychological, and adjunctive therapies to address the multifactorial nature of BMS. Full article
13 pages, 611 KB  
Article
Long-Term Outcomes of Epidural Motor Cortex Stimulation for Refractory Chronic Neuropathic Orofacial Pain
by Marina Raguž, Marko Tarle, Petar Marčinković, Sven Krušić, Domagoj Dlaka, Tonko Marinović and Darko Chudy
Life 2026, 16(4), 651; https://doi.org/10.3390/life16040651 - 12 Apr 2026
Viewed by 747
Abstract
Background: Epidural motor cortex stimulation (MCS) is an established neuromodulatory option for refractory neuropathic pain; however, structured data on long-term outcomes, stimulation dependency, and real-world device management remain limited, particularly in chronic neuropathic orofacial pain. Methods: This retrospective single-center cohort study included patients [...] Read more.
Background: Epidural motor cortex stimulation (MCS) is an established neuromodulatory option for refractory neuropathic pain; however, structured data on long-term outcomes, stimulation dependency, and real-world device management remain limited, particularly in chronic neuropathic orofacial pain. Methods: This retrospective single-center cohort study included patients with refractory neuropathic orofacial pain treated with epidural MCS at a tertiary neurosurgical center. Clinical data were extracted from medical records and longitudinal follow-up documentation. Pain intensity was assessed using a unified 0–10 numerical rating scale (NRS/VAS) at baseline, best achieved response, and last follow-up. Responder status was defined at the last follow-up (≥50% pain reduction from baseline). Secondary outcomes included stimulation dependency during OFF periods, reprogramming burden, device-related events, and safety. Results: Ten patients (6 women, 4 men; mean age 61.5 ± 8.6 years) were followed for a mean of 7.6 ± 6.3 years (range 2–22 years), with 70% exceeding five years of follow-up. Baseline pain intensity (8.8 ± 0.4) decreased to 4.6 ± 0.8 at the best achieved response and remained lower at last follow-up (5.6 ± 0.9). At the last follow-up, eight patients (80%) were classified as partial responders (30–49% pain reduction), while two (20%) were classified as non-responders. Clinically relevant worsening during stimulator OFF periods occurred in 70% of patients. Reprogramming was required in all patients, and 60% underwent battery replacement. No clinically significant stimulation-related adverse effects were observed. Conclusions: Epidural MCS was associated with sustained pain reduction over extended follow-up. These findings support the interpretation of MCS as a chronic neuromodulatory therapy requiring ongoing stimulation, individualized programming, and long-term device management, contributing clinically relevant long-term evidence to the evolving role of neuromodulation in refractory chronic neuropathic pain. Full article
Show Figures

Figure 1

55 pages, 2022 KB  
Review
Post-COVID-19 Jaw Osteonecrosis: A Narrative Review
by George Cătălin Alexandru, Loredana-Neli Gligor, Doina Chioran, Ciprian I. Roi, Mircea Riviș, Marius Octavian Pricop, Andrei Urîtu, Aliteia-Maria Pacnejer, Horațiu Cristian Manea and Tudor Rareş Olariu
Medicina 2026, 62(4), 641; https://doi.org/10.3390/medicina62040641 - 27 Mar 2026
Cited by 2 | Viewed by 1655
Abstract
Background and Objectives: Osteonecrosis of the jaw (ONJ) occurring after infection with SARS-CoV-2 has emerged as an increasingly reported complication in the post-COVID-19 era. Post-COVID-19 osteonecrosis of the jaw (PC-ONJ) has been described in association with both COVID-19-associated mucormycosis (CAM) and non-fungal [...] Read more.
Background and Objectives: Osteonecrosis of the jaw (ONJ) occurring after infection with SARS-CoV-2 has emerged as an increasingly reported complication in the post-COVID-19 era. Post-COVID-19 osteonecrosis of the jaw (PC-ONJ) has been described in association with both COVID-19-associated mucormycosis (CAM) and non-fungal phenotypes. This narrative review aims to synthesize and critically analyze the available evidence regarding terminology and classification, epidemiology and risk factors, pathophysiological mechanisms, clinical and imaging characteristics, diagnostic challenges, and management strategies relevant to oral and maxillofacial surgery practice. Materials and Methods: An extensive literature search was conducted in the PubMed/MEDLINE, Scopus, Web of Science, ScienceDirect, and Google Scholar databases. The search targeted peer-reviewed publications published between 2020 and 2025, reflecting the post-pandemic emergence of this clinical spectrum. Original studies, systematic and narrative reviews, multicenter case series, consensus guidelines, and well-documented case reports were considered. Results: Available data, largely derived from case reports and small series, demonstrate a predominance of maxillary involvement and frequent association with diabetes mellitus and systemic corticosteroid therapy. Proposed mechanisms include COVID-19-associated endothelial dysfunction, microvascular thrombosis, immune dysregulation, metabolic imbalance, and treatment-related effects. Clinically, patients may present with persistent orofacial pain, tooth mobility, exposed or probeable bone, and frequent sinonasal extension, with symptoms sometimes preceding bone exposure. Diagnostic challenges arise from the overlap with medication-related osteonecrosis of the jaw (MRONJ), osteoradionecrosis (ORN), and chronic osteomyelitis. Imaging is essential for assessing disease extent but remains insufficient for etiologic differentiation, making histopathological examination and targeted microbiological investigations necessary, particularly to exclude invasive fungal infection. Conclusions: Management must be etiology-driven. CAM requires urgent antifungal therapy combined with surgical debridement, whereas non-fungal forms are generally managed with conservative surgery and appropriate antimicrobial stewardship. Standardized diagnostic criteria and prospective multicenter studies are needed to reduce nosological ambiguity and optimize clinical decision-making in this emerging post-viral condition. Full article
(This article belongs to the Special Issue Research on Oral and Maxillofacial Surgery)
Show Figures

Figure 1

19 pages, 723 KB  
Systematic Review
Biopsychosocial Predictors of Pain Persistence and Pain Chronification in Temporomandibular Disorders: A Systematic Review
by Piotr Seweryn, Marta Waliszewska-Prosol, Marcin Derwich, Anna Paradowska-Stolarz, Magdalena Gebska and Mieszko Wieckiewicz
J. Clin. Med. 2026, 15(7), 2498; https://doi.org/10.3390/jcm15072498 - 25 Mar 2026
Cited by 1 | Viewed by 1136
Abstract
Background/Objectives: Temporomandibular disorders (TMD) are common causes of orofacial pain, but their clinical course varies, with some patients developing persistent symptoms. Evidence supports a biopsychosocial model of pain chronification, yet prognostic factors for pain persistence in TMD remain insufficiently synthesized. This systematic review [...] Read more.
Background/Objectives: Temporomandibular disorders (TMD) are common causes of orofacial pain, but their clinical course varies, with some patients developing persistent symptoms. Evidence supports a biopsychosocial model of pain chronification, yet prognostic factors for pain persistence in TMD remain insufficiently synthesized. This systematic review aimed to identify biological, psychological, and social predictors associated with pain persistence and chronicity in painful TMD. Methods: This review was conducted in accordance with PRISMA 2020 guidelines and registered in PROSPERO (CRD420261286566). MEDLINE, Embase, and Web of Science were searched for studies published between January 2010 and December 2025. Eligible studies included adult patients with painful TMD and assessed baseline biopsychosocial predictors of pain persistence or chronicity at follow-up ≥ 3 months. Risk of bias was assessed using QUIPS and PROBAST. Due to heterogeneity across studies, findings were synthesized narratively. Results: Six prospective cohort studies were included, with follow-up durations ranging from 6 to 24 months. Psychological factors, particularly pain catastrophizing and depression, were associated with increased risk of pain persistence. Higher baseline pain intensity and widespread pain also showed prognostic value. Sleep-related and behavioral factors demonstrated inconsistent associations, and social predictors were rarely examined. The certainty of evidence ranged from moderate for catastrophizing and pain intensity to very low for sleep-related and occlusal factors. Conclusions: Pain persistence in TMD is influenced by multiple biopsychosocial factors. Psychological variables, especially catastrophizing and depression, appear to be the most consistent predictors, although this finding should be interpreted with caution, given the small number of included studies. These findings highlight the importance of comprehensive biopsychosocial assessment in patients with painful TMD and the need for further longitudinal research. Full article
Show Figures

Graphical abstract

24 pages, 2718 KB  
Article
Doxazosin Alleviates Chronic Orofacial Pain
by Karin N. Westlund, Bingye Xue and Sabrina L. McIlwrath
Int. J. Mol. Sci. 2026, 27(5), 2142; https://doi.org/10.3390/ijms27052142 - 25 Feb 2026
Cited by 1 | Viewed by 650
Abstract
Central to the linkage of pain circuitry with the limbic system is its initial NAα2-mediated antinociceptive effect in acute pain models, followed by contradictory pronociceptive activation by the locus coeruleus seen in chronic pain models. Rats with a stable, long-term (>10 weeks) inflammatory [...] Read more.
Central to the linkage of pain circuitry with the limbic system is its initial NAα2-mediated antinociceptive effect in acute pain models, followed by contradictory pronociceptive activation by the locus coeruleus seen in chronic pain models. Rats with a stable, long-term (>10 weeks) inflammatory compression of the trigeminal infraorbital nerve (FRICT-ION) preclinical model were given daily doxazosin, a slow-release NAα1 receptor antagonist, in weeks 8–10. Facial hypersensitivity was reversed back to baseline in male and female rats, but anxiety was only reduced in male animals. Doxazosin-decreased astrocytic activation was indicated by a decrease in both intracranial cathepsin B imaging in vivo and GFAP immunostaining in the somatosensory cortex and hippocampus. Doxazosin reduction in NAα1 receptor activation diminished glial-neuronal interactions, resulting in downstream reduction in pain-related behaviors. Other significant differences by sex included improved elevated zero maze anxiety measures only in males, and improved novel recognition scores only in females. Elevated thymus chemokine CXCL7 levels were reduced by doxazosin but only in male rats. These sexually dimorphic contradictions further complicate the understanding of the noradrenergic system’s involvement in nociception. The findings indicate that by reducing NAα1 receptor drive with doxazosin, the role of the locus coeruleus can be shifted back to NAα2-receptor-mediated pain inhibition. Full article
Show Figures

Figure 1

9 pages, 198 KB  
Case Report
Burning Mouth Syndrome as a Central Pain Disorder: A Case Study Demonstrating Response to Occipital Nerve Block Treatment
by Shachar Zion Shemesh, Paz Kelmer and Lior Ungar
Dent. J. 2026, 14(2), 81; https://doi.org/10.3390/dj14020081 - 2 Feb 2026
Viewed by 960
Abstract
Background: Burning Mouth Syndrome (BMS) is a chronic orofacial pain condition characterized by a burning sensation in the oral cavity without identifiable lesions. It predominantly affects women (especially postmenopausal) but can occur in men. BMS is considered a multifactorial neuropathic pain disorder involving [...] Read more.
Background: Burning Mouth Syndrome (BMS) is a chronic orofacial pain condition characterized by a burning sensation in the oral cavity without identifiable lesions. It predominantly affects women (especially postmenopausal) but can occur in men. BMS is considered a multifactorial neuropathic pain disorder involving both peripheral small-fiber neuropathy and central dysregulation, often accompanied by taste alterations (dysgusia) and xerostomia despite normal oral exams. Treatment is challenging, with modest responses to agents like clonazepam, tricyclic antidepressants, or gabapentinoids. Observations: We present a 67-year-old male with recalcitrant primary BMS who showed complete remission temporally associated with occipital nerve blockade, likely affecting central trigeminocervical pathways. Initial therapy with amitriptyline (25 mg) and gabapentin (900 mg/day) yielded ~30% pain relief. Given suspected central sensitization, greater and lesser occipital nerve (GON) blocks were administered in series. After the first, second, and third ON blocks, pain was reduced by ~50%, 80%, and 100%, respectively. Remission persisted at one-year follow-up under continued medications. A mild recurrence (~20% of baseline pain) responded fully to a fourth GON block, maintaining another year of pain-free status. Lessons: This case underscores the complex central mechanisms in BMS and illustrates that modulating central pain circuits via occipital nerve blockade, through trigeminocervical convergence mechanisms, without direct trigeminal intervention. We discuss the diagnostic challenges of BMS, the rationale of occipital neuromodulation, and how this novel therapeutic strategy compares with current literature, supporting the hypothesis of central sensitization in BMS. Full article
20 pages, 1354 KB  
Review
Central and Peripheral Sensitization in Temporomandibular Disorders: Proposed Mechanisms of Botulinum Toxin Therapy
by Basit Ali Chaudhry, Christopher L. Robinson, Edoardo Caronna, Freda Dodd-Glover, Amrittej Singh Virk, Mario Fernando Prieto Peres, Hope L. O’Brien, Marcela Romero-Reyes and Sait Ashina
Toxins 2026, 18(1), 28; https://doi.org/10.3390/toxins18010028 - 6 Jan 2026
Cited by 3 | Viewed by 2659
Abstract
Temporomandibular disorders (TMDs) are common musculoskeletal chronic orofacial pain conditions involving peripheral and central sensitization within trigeminal nociceptive pathways, manifesting as mechanical allodynia and functional impairment. Botulinum toxin type A (BoNT-A) has been explored as a treatment targeting both muscle hyperactivity and nociceptive [...] Read more.
Temporomandibular disorders (TMDs) are common musculoskeletal chronic orofacial pain conditions involving peripheral and central sensitization within trigeminal nociceptive pathways, manifesting as mechanical allodynia and functional impairment. Botulinum toxin type A (BoNT-A) has been explored as a treatment targeting both muscle hyperactivity and nociceptive modulation. Preclinical and clinical evidence demonstrate that BoNT-A reduces peripheral neurotransmitter release, neurogenic inflammation, and central neuronal excitability, leading to attenuation of mechanical allodynia in TMD models and patients. Clinical trials show modest and variable analgesic effects, with patients displaying sensory sensitization appearing to respond more favorably, though methodological heterogeneity limits definitive conclusions. Safety concerns related to muscle weakening, changes in bone density, and structural changes underscore the need for standardized protocols optimizing dosing and monitoring, in addition to prospective studies. These findings suggest that BoNT-A may serve as an adjunctive, mechanism-based therapy within multimodal TMD management. Future research should focus on standardized sensory phenotyping and trial design to clarify BoNT-A’s role in modulating central sensitization and improving patient outcomes. Full article
Show Figures

Figure 1

17 pages, 842 KB  
Review
Glial Activation, Neuroinflammation, and Loss of Neuroprotection in Chronic Pain: Cellular Mechanisms and Emerging Therapeutic Strategies
by Alyssa McKenzie, Rachel Dombrower, Nitchanan Theeraphapphong, Sophia McKenzie and Munther A. Hijazin
Biomedicines 2026, 14(1), 58; https://doi.org/10.3390/biomedicines14010058 - 26 Dec 2025
Cited by 13 | Viewed by 2381
Abstract
Chronic pain is increasingly regarded as a condition of glia–neuronal dysregulation driven by persistent neuroinflammatory signaling. Following injury to nerves or tissues, glial cells, including astrocytes or satellite glial cells, undergo changes in their phenotype, thereby amplifying painful stimuli mediated by cytokines, chemokines, [...] Read more.
Chronic pain is increasingly regarded as a condition of glia–neuronal dysregulation driven by persistent neuroinflammatory signaling. Following injury to nerves or tissues, glial cells, including astrocytes or satellite glial cells, undergo changes in their phenotype, thereby amplifying painful stimuli mediated by cytokines, chemokines, or ATP signaling. In response to injuries, activated microglia release several mediators such as BDNF, IL-1β, or TNF-α, thereby disrupting chloride homeostasis and inducing disinhibition in the dorsal horn, and sustaining maladaptive neuroimmune activity. Dysfunction of astrocytes, characterized by impaired glutamate clearance via excitatory amino acid transporter 2 and elevated C-X-C motif chemokine ligand 1 (CXCL1) and ATP release, drives neuronal sensitization, loss of neuroprotective metabolic support, and persistence of pain. In peripheral ganglia, connexin–43–mediated satellite glial cell coupling leads to hyperexcitability, resulting in neuropathic and orofacial pain and contributing to peripheral neuroinflammation. Presently, there is no unified framework for glial cell types, and the molecular mechanisms underlying microglial, astrocyte, and satellite glial cell contributions to the transition to chronic pain from acute pain are not completely elucidated. This review synthesizes current evidence on cellular and molecular mechanisms linking glial reactivity to pain chronification through sustained neuroinflammatory remodeling and impaired neuroprotection. It evaluates therapeutic strategies, including purinergic receptor P2X4 and toll-like receptor 4 antagonists, to metabolic reprogramming, exosome therapy, and neuromodulation, aimed at restoring homeostatic glial function and re-establishing neuroprotective glia–neuron interactions. A deeper understanding of the temporal and spatial dynamics of glial activation may enable personalized, non-opioid interventions that not only achieve durable analgesia but also prevent progressive neuroinflammatory damage and support long-term functional recovery. Full article
(This article belongs to the Special Issue Neuroinflammation and Neuroprotection)
Show Figures

Figure 1

15 pages, 768 KB  
Article
Cross-Cultural Differences and Clinical Presentations in Burning Mouth Syndrome: A Cross-Sectional Comparative Study of Italian and Romanian Outpatient Settings
by Claudiu Gabriel Ionescu, Gennaro Musella, Federica Canfora, Cristina D’Antonio, Lucia Memé, Stefania Leuci, Luca D’Aniello, Ioanina Parlatescu, Lorenzo Lo Muzio, Michele Davide Mignogna, Serban Tovaru and Daniela Adamo
J. Clin. Med. 2025, 14(16), 5805; https://doi.org/10.3390/jcm14165805 - 16 Aug 2025
Viewed by 1611
Abstract
Background/Objectives: Burning Mouth Syndrome (BMS) is a chronic orofacial pain disorder characterized by persistent intraoral burning sensations without visible mucosal lesions. Although its biopsychosocial complexity is increasingly recognized, cross-cultural comparison data remain limited. Methods: This cross-sectional study assessed 60 patients with [...] Read more.
Background/Objectives: Burning Mouth Syndrome (BMS) is a chronic orofacial pain disorder characterized by persistent intraoral burning sensations without visible mucosal lesions. Although its biopsychosocial complexity is increasingly recognized, cross-cultural comparison data remain limited. Methods: This cross-sectional study assessed 60 patients with BMS (30 Italian, 30 Romanian) who underwent standardized clinical, psychological, and sleep evaluations. Data collected included sociodemographics, clinical characteristics, diagnostic history, comorbidities, and symptomatology. The assessment tools used included the Numeric Rating Scale (NRS), Short Form of the McGill Pain Questionnaire (SF-MPQ), Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale (HAM-D), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS). Statistical comparisons were conducted using Mann–Whitney U and Fisher’s exact tests with Bonferroni correction. Results: No significant differences were observed in age, sex, or body mass index. Italian patients had fewer years of education (p = 0.001), higher pain intensity (NRS, p < 0.001), poorer sleep quality (PSQI, ESS, p = 0.001), and more frequent pre-existing sleep disorders (p < 0.001). Romanian patients showed higher levels of anxiety (HAM-A, p < 0.001), longer diagnostic delays (p = 0.002), and more dysesthetic or perceptual symptoms, including tingling and oral dysmorphism (p < 0.05). Stressful events before onset were more common among Romanians (p < 0.001), while Italians more often received a correct diagnosis at first consultation (p = 0.005). Conclusions: This first cross-national comparison of BMS in Western and Eastern Europe shows that cultural, healthcare, and clinician education differences can shape symptom profiles, comorbidities, and diagnostic delays, underscoring the need for personalized, country-specific management strategies. Full article
(This article belongs to the Special Issue New Perspective of Oral and Maxillo-Facial Surgery)
Show Figures

Figure 1

14 pages, 286 KB  
Hypothesis
Botulinum Toxin-A, Generating a Hypothesis for Orofacial Pain Therapy
by Yair Sharav, Rafael Benoliel and Yaron Haviv
Toxins 2025, 17(8), 389; https://doi.org/10.3390/toxins17080389 - 4 Aug 2025
Cited by 2 | Viewed by 3575
Abstract
Orofacial pain encompasses a spectrum of disorders ranging from musculoskeletal disorders, such as myofascial pain, and temporomandibular disorders to neuropathic situations, such as trigeminal neuralgia and painful post-traumatic trigeminal neuropathy, and neurovascular pain such as orofacial migraine and cluster orofacial pain. Each require [...] Read more.
Orofacial pain encompasses a spectrum of disorders ranging from musculoskeletal disorders, such as myofascial pain, and temporomandibular disorders to neuropathic situations, such as trigeminal neuralgia and painful post-traumatic trigeminal neuropathy, and neurovascular pain such as orofacial migraine and cluster orofacial pain. Each require tailored prophylactic pharmacotherapy, such as carbamazepine, gabapentin, pregabalin, amitriptyline, metoprolol, and topiramate. Yet a substantial subset of patients remains refractory. Botulinum toxin type A (BoNT-A) has demonstrated growing efficacy in the treatment of multiple forms of orofacial pain, which covers the whole range of these disorders. We describe the analgesic properties of BoNT-A for each of the three following orofacial pain disorders: neuropathic, myofascial, and neurovascular. Then, we conclude with a section on the neuromodulatory mechanisms of BoNT-A. This lays the basis for the generation of a hypothesis for the segmental therapeutic action of BoNT-A on the whole range of orofacial pain disorders. In addition, the advantage of BoNT-A for providing a safe sustained effect after a single application for chronic pain prophylaxis is discussed, as opposed to the daily use of current conventional prophylactic medications. Finally, we summarize the clinical applications of BoNT-A for chronic orofacial pain therapy. Full article
17 pages, 890 KB  
Article
Multimodal Management and Prognostic Factors in Post-Traumatic Trigeminal Neuropathic Pain Following Dental Procedures: A Retrospective Study
by Hyun-Jeong Park, Jong-Mo Ahn, Young-Jun Yang and Ji-Won Ryu
Appl. Sci. 2025, 15(15), 8480; https://doi.org/10.3390/app15158480 - 30 Jul 2025
Viewed by 5006
Abstract
Background: Post-traumatic trigeminal neuropathic pain (PTTNP) is a chronic condition often caused by dental procedures such as implant placement or tooth extraction. It involves persistent pain and sensory disturbances, negatively affecting the quality of life of patients. Methods: This retrospective observational study was [...] Read more.
Background: Post-traumatic trigeminal neuropathic pain (PTTNP) is a chronic condition often caused by dental procedures such as implant placement or tooth extraction. It involves persistent pain and sensory disturbances, negatively affecting the quality of life of patients. Methods: This retrospective observational study was conducted at Chosun University Dental Hospital and included 120 patients diagnosed with PTTNP involving the orofacial region. Patient data were collected between January 2014 and December 2023. Among them, 79 patients (65.8%) developed PTTNP following dental implant placement, with a total of 121 implants analyzed. The inferior alveolar nerve was most frequently involved. Clinical factors, including the time to treatment, removal of the causative factor, the Sunderland injury grade, and the type of treatment, were evaluated. Pain intensity and sensory changes were assessed using the visual analog scale (VAS). Results: Treatment initiated within the early post-injury period, commonly regarded as within three months, and implant removal tended to improve outcomes. Pharmacological therapy was the most commonly employed modality, particularly gabapentinoids (e.g., gabapentin, pregabalin) and tricyclic antidepressants such as amitriptyline. However, combined therapy, which included pharmacologic, physical, and surgical approaches, was associated with the greatest sensory improvement. Conclusions: Prompt, multidisciplinary intervention may enhance recovery in patients with PTTNP. Implant-related injuries require careful management, and multimodal strategies appear more effective than monotherapies. Full article
(This article belongs to the Special Issue Oral Diseases: Diagnosis and Therapy)
Show Figures

Figure 1

Back to TopTop