RESUMO
ABSTRACT: The co-occurrence of bruxism, temporomandibular disorders (TMDs), and headache is common in patients. However, there is conflicting evidence regarding whether this association is simply a result of their high prevalence or whether there are indeed causal relationships. This review provides an overview of the current state of research while taking into account the controversies surrounding research methods, particularly in definitions and diagnostic standards. Bruxism-defined as repetitive jaw muscle activity during sleep or wakefulness-is not a painful disorder but may-particularly in co-occurrence with TMD-worsen pre-existing headache. It seems important to differentiate between sleep and awake bruxism because of different impact on pathophysiological processes in different primary headache disorders such as migraine and tension-type headache. Temporomandibular disorder is a heterogenous entity with both myofascial and arthrogenous types of pain in addition to nonpainful disorders. Research suggests a correlation between TMD pain and migraine, as well as between awake bruxism and tension-type headache. However, psychosocial factors may act as confounders in these relationships. Determining causality is challenging because of the limited number of experimental and clinical studies conducted on this topic. The main finding is an apparent lack of consensus on the definition and assessment criteria for bruxism. Treatment wise, it is important to differentiate all 3 conditions because treatment of one condition may have an effect on the other 2 without proving causality. For future research, it is crucial to establish greater consistency and applicability in diagnostic procedures and definitions. In addition, more experimental and clinical studies investigating the question of causality are needed.
RESUMO
The transcription factor Interferon Regulatory Factor 4 (IRF4) is central in control of T cell activation and differentiation. Deficiency of IRF4 results in severe immune deficiency and affects maturation and function of most if not all T cell subsets. Here we use mouse infection models for Citrobacter rodentium and Strongyloides ratti to analyze the function of IRF4 in T helper (Th) 17 and Th2 cell responses, respectively. IRF4 deficient mice were impaired in the control of both pathogens, failed to mount Th17 and Th2 cell responses and showed impaired recruitment of T helper cells to the intestine, the infection site of both pathogens. Compromised intestinal migration was associated with reduced expression of the intestinal homing receptors α4ß7 integrin, CCR9 and GPR15. Identification of IRF4 binding sites in the gene loci of these receptors suggests a direct control of their expression by IRF4. Competitive T cell transfer assays further demonstrated that loss of one functional Irf4 allele already affected intestinal accumulation and Th2 and Th17 cell generation, indicating that lower IRF4 levels are of disadvantage for Th2 and Th17 cell differentiation as well as their migration to the intestine. Conversion of peripheral CD4+ T cells from an Irf4 wildtype to an Irf4 heterozygous or from an Irf4 heterozygous to a homozygous mutant genotype after C. rodentium or S. ratti infection did not reduce their capacity to produce Th17 or Th2 cytokines and only partially affected their persistence in the intestine, revealing that IRF4 is not essential for maintenance of the Th2 and Th17 phenotype and for survival of these T helper cells in the intestine. In conclusion, we demonstrate that the expression levels of IRF4 determine Th2 and Th17 cell differentiation and their intestinal accumulation but that IRF4 expression is not crucial for Th2 and Th17 cell survival.
