Myofascial pain syndrome is an important health problem. It affects a majority of the general population, impairs mobility, causes pain, and reduces the overall sense of well-being. Underlying this syndrome is the existence of painful taut bands of muscle that contain discrete, hypersensitive foci called myofascial trigger points. In spite of the significant impact on public health, a clear mechanistic understanding of the disorder does not exist. This is likely due to the complex nature of the disorder which involves the integration of cellular signaling, excitation-contraction coupling, neuromuscular inputs, local circulation, and energy metabolism. The difficulties are further exacerbated by the lack of an animal model for myofascial pain to test mechanistic hypothesis. In this review, current theories for myofascial pain are presented and their relative strengths and weaknesses are discussed. Based on new findings linking mechanoactivation of reactive oxygen species signaling to destabilized calcium signaling, we put forth a novel mechanistic hypothesis for the initiation and maintenance of myofascial trigger points. It is hoped that this lays a new foundation for understanding myofascial pain syndrome and how current therapies work, and gives key insights that will lead to the improvement of therapies for its treatment.

The neurotransmitters at synapses in taste buds are not yet known with confidence. Here we report a new calcium-imaging technique for taste buds that allowed us to test for the presence of glutamate receptors (GluRs) in living isolated tissue preparations. Taste cells of rat foliate papillae were loaded with calcium green dextran (CaGD). Lingual slices containing CaGD-labeled taste cells were imaged with a scanning confocal microscope and superfused with glutamate (30 M to 1 mM), kainate (30 and 100 M), AMPA (30 and 100 M), or NMDA (100 M). Responses were observed in 26% of the cells that were tested with 300 M glutamate. Responses to glutamate were localized to the basal processes and cell bodies, which are synaptic regions of taste cells. Glutamate responses were dose-dependent and were induced by concentrations as low as 30 M. The non-NMDA receptor antagonists CNQX and GYKI 52466 reversibly blocked responses to glutamate. Kainate, but not AMPA, also elicited Ca 2ϩ responses. NMDA stimulated increases in [Ca 2ϩ ] i when the bath medium was modified to optimize for NMDA receptor activation. The subset of cells that responded to glutamate was either NMDA-unresponsive (54%) or NMDA-responsive (46%), suggesting that there are presumably two populations of glutamate-sensitive taste cells-one with NMDA receptors and the other without NMDA receptors. The function of GluRs in taste buds is not yet known, but the data suggest that glutamate is a neurotransmitter there. GluRs in taste cells might be presynaptic autoreceptors or postsynaptic receptors at afferent or efferent synapses.

The heart requires a large amount of energy to sustain both ionic homeostasis and contraction. Under normal conditions, adenosine triphosphate (ATP) production meets this demand. Hence, there is a complex regulatory system that adjusts energy production to meet this demand. However, the mechanisms for this control are a topic of active debate. Energy metabolism can be divided into three main stages: substrate delivery to the tricarboxylic acid (TCA) cycle, the TCA cycle, and oxidative phosphorylation. Each of these processes has multiple control points and exerts control over the other stages. This review discusses the basic stages of energy metabolism, mechanisms of control, and the mathematical and computational models that have been used to study these mechanisms.