Preclinical orofacial pain assays and measures and chronic primary orofacial pain research: where we are and where we need to go.

Chronic primary orofacial pain (OFP) conditions such as painful temporomandibular disorders (pTMDs; i.e., myofascial pain and arthralgia), idiopathic trigeminal neuralgia (TN), and burning mouth syndrome (BMS) are seemingly idiopathic, but evidence support complex and multifactorial etiology and pathophysiology.

The Adaptive, Pain Sensitive, and Global Symptoms Clusters: Evidence from a Patient-Based Study.

Objectives: The largest epidemiologic study conducted about painful temporomandibular disorders (pTMDs) to date identified 3 clusters of individuals with similar symptoms-adaptive, pain sensitive, and global symptoms-which hold promise as a means of personalizing pain care. Our goal was to compare the clinical and psychological characteristics that are consistent with a pTMD clinical examination among patients who are seeking care and assigned to the different clusters.

Methods: This cross-sectional study used data from the medical records of patients attending Duke Innovative Pain Therapies between August 2017 and April 2021 who received a pTMD diagnosis (i.

Fibromyalgia patients with elevated levels of anti-satellite glia cell immunoglobulin G antibodies present with more severe symptoms.

Transferring fibromyalgia patient immunoglobulin G (IgG) to mice induces pain-like behaviour, and fibromyalgia IgG binds mouse and human satellite glia cells (SGCs). These findings suggest that autoantibodies could be part of fibromyalgia pathology. However, it is unknown how frequently fibromyalgia patients have anti-SGC antibodies and how anti-SGC antibodies associate with disease severity.

Unbiased immune profiling reveals a natural killer cell-peripheral nerve axis in fibromyalgia.

The pathophysiology of fibromyalgia syndrome (FMS) remains elusive, leading to a lack of objective diagnostic criteria and targeted treatment. We globally evaluated immune system changes in FMS by conducting multiparametric flow cytometry analyses of peripheral blood mononuclear cells and identified a natural killer (NK) cell decrease in patients with FMS. Circulating NK cells in FMS were exhausted yet activated, evidenced by lower surface expression of CD16, CD96, and CD226 and more CD107a and TIGIT.

Mast cell stabilizer ketotifen fumarate reverses inflammatory but not neuropathic-induced mechanical pain in mice.

Introduction: Mast cell (MC) activation could establish a positive feedback loop that perpetuates inflammation and maintains pain. Stabilizing MCs with ketotifen fumarate (KF) may disrupt this loop and relieve pain.

Objective: We aimed to test the effect of treatment with KF in pain assays in mice and in a case series of patients with chronic widespread pain.

The Quebec Low Back Pain Study: a protocol for an innovative 2-tier provincial cohort.

Introduction: The neurobiological mechanisms underlying recovery from or persistence of low back pain (LBP) remain misunderstood, limiting progress toward effective management. We have developed an innovative two-tier design to study the transition from acute to chronic LBP. The objective of the first tier is to create a provincial web-based infrastructure to recruit and monitor the trajectory of individuals with acute LBP.

Clinical predictors of persistent temporomandibular disorder in people with first-onset temporomandibular disorder: A prospective case-control study.

Background: When patients first develop a painful temporomandibular disorder (TMD) and seek care, 1 priority for clinicians is to assess prognosis. The authors aimed to develop a predictive model by using biopsychosocial measures from the Diagnostic Criteria for Temporomandibular Disorders (DC-TMD) to predict risk of developing TMD symptom persistence.

Methods: At baseline, trained examiners identified 260 participants with first-onset TMD classified by using DC-TMD-compliant protocols.

Low back pain.

Low back pain affects individuals of all ages and is a leading contributor to disease burden worldwide. Despite advancements in assessment and treatment methods, the management of low back pain remains a challenge for researchers and clinicians alike. One reason for the limited success in identifying effective treatments is the large variation in the manifestations, possible causes, precipitating and maintaining factors, course, prognosis and consequences in terms of activity interference and quality of life.

Genome-wide association reveals contribution of MRAS to painful temporomandibular disorder in males.

Painful temporomandibular disorders (TMDs) are the leading cause of chronic orofacial pain, but its underlying molecular mechanisms remain obscure. Although many environmental factors have been associated with higher risk of developing painful TMD, family and twin studies support a heritable genetic component as well. We performed a genome-wide association study assuming an additive genetic model of TMD in a discovery cohort of 999 cases and 2031 TMD-free controls from the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study.

Human pain genetics database: a resource dedicated to human pain genetics research.

The Human Pain Genetics Database (HPGDB) is a comprehensive variant-focused inventory of genetic contributors to human pain. After curation, the HPGDB currently includes 294 studies reporting associations between 434 distinct genetic variants and various pain phenotypes. Variants were then submitted to a comprehensive analysis.

Epiregulin and EGFR interactions are involved in pain processing.

The EGFR belongs to the well-studied ErbB family of receptor tyrosine kinases. EGFR is activated by numerous endogenous ligands that promote cellular growth, proliferation, and tissue regeneration. In the present study, we have demonstrated a role for EGFR and its natural ligand, epiregulin (EREG), in pain processing.

GWAS Identifies New Loci for Painful Temporomandibular Disorder: Hispanic Community Health Study/Study of Latinos.

Temporomandibular disorder (TMD) is a musculoskeletal condition characterized by pain and reduced function in the temporomandibular joint and/or associated masticatory musculature. Prevalence in the United States is 5% and twice as high among women as men. We conducted a discovery genome-wide association study (GWAS) of TMD in 10,153 participants (769 cases, 9,384 controls) of the US Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

Genetic predictors of human chronic pain conditions.

Chronic pain conditions are multifactorial disorders with a high frequency in the population. Their pathophysiology is often unclear, and treatment is inefficient. During the last 20years, genetic linkage analysis and association studies have made considerable strides toward identifying key molecular contributors to the onset and maintenance of chronic pain.

Prevalence of temporomandibular disorders in postmenopausal women and relationship with pain and HRT.

The prevalence of temporomandibular disorders (TMD) is higher in females, reaching their high peak during reproductive years, probably because of the action of some female hormones, which alter pain threshold. This study aimed to investigate the prevalence of TMD in postmenopausal women and its relationship with pain and hormone replacement therapy (HRT). In total, 284 patients were evaluated and classified using the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD).

Painful Temporomandibular Disorder: Decade of Discovery from OPPERA Studies.

In 2006, the OPPERA project (Orofacial Pain: Prospective Evaluation and Risk Assessment) set out to identify risk factors for development of painful temporomandibular disorder (TMD). A decade later, this review summarizes its key findings. At 4 US study sites, OPPERA recruited and examined 3,258 community-based TMD-free adults assessing genetic and phenotypic measures of biological, psychosocial, clinical, and health status characteristics.

Modification of COMT-dependent pain sensitivity by psychological stress and sex.

Catecholamine-O-methyltransferase (COMT) is a polymorphic gene whose variants affect enzymatic activity and pain sensitivity via adrenergic pathways. Although COMT represents one of the most studied genes in human pain genetics, findings regarding its association with pain phenotypes are not always replicated. Here, we investigated if interactions among functional COMT haplotypes, stress, and sex can modify the effect of COMT genetic variants on pain sensitivity.

COMT gene locus: new functional variants.

Catechol-O-methyltransferase (COMT) metabolizes catecholaminergic neurotransmitters. Numerous studies have linked COMT to pivotal brain functions such as mood, cognition, response to stress, and pain. Both nociception and risk of clinical pain have been associated with COMT genetic variants, and this association was shown to be mediated through adrenergic pathways.

Molecular genetic mechanisms of allelic specific regulation of murine Comt expression.

A functional allele of the mouse catechol-O-methyltransferase (Comt) gene is defined by the insertion of a B2 short interspersed repeat element in its 3'-untranslated region (UTR). This allele has been associated with a number of phenotypes, such as pain and anxiety. In comparison with mice carrying the ancestral allele (Comt+), Comt B2i mice show higher Comt mRNA and enzymatic activity levels.

Subgrouping of low back pain patients for targeting treatments: evidence from genetic, psychological, and activity-related behavioral approaches.

Introduction: Many patients with low back pain (LBP) are treated in a similar manner as if they were a homogenous group. However, scientific evidence is available that pain is a complex perceptual experience influenced by a wide range of genetic, psychological, and activity-related factors. The leading question for clinical practice should be what works for whom.

Effect of surface treatments on the bond strength of different resin teeth to complete denture base material.

Although different commercial brands of artificial teeth are available in the market, debonding from the denture base is still an issue when rehabilitating edentulous patients with conventional or implant-supported complete dentures. The purpose of this study was to investigate the effect of surface treatments on the bond strength of four artificial teeth brands to a denture base material polymerized by microwave energy. Forty anterior artificial teeth of each brand (Biolux, Trilux, Biotone IPN, and Vipi Dent Plus) were bonded to denture base material (VipiWave).

Influence of different flasking and polymerizing methods on the occlusal vertical dimension of complete dentures.

The flasking and polymerization technique for resins can introduce stresses during processing which may lead to denture base distortions, artificial teeth displacement and increases in the occlusal vertical dimension (OVD). This study investigated whether the association of microwave heat-activation (MH) and bimaxillary flasking (BF) minimizes the possible increases in OVD after prostheses processing. Forty pairs of complete dentures were waxed with the artificial teeth in closed occlusion and divided into four groups according to investing and heating methods: G1 (control) = monomaxillary/water bath; G2 = monomaxillary/microwave; G3 = bimaxillary/water bath and G4 = bimaxillary/microwave.