Pain
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Individual vulnerability factors influencing the function of the hypothalamic-pituitary-adrenal axis may contribute to the risk of the development of persistent musculoskeletal pain after traumatic stress exposure. The objective of the study was to evaluate the association between polymorphisms in the gene encoding FK506 binding protein 51, FKBP5, a glucocorticoid receptor co-chaperone, and musculoskeletal pain severity 6 weeks after 2 common trauma exposures. The study included data from 2 prospective emergency department-based cohorts: a discovery cohort (n=949) of European Americans experiencing motor vehicle collision and a replication cohort of adult European American women experiencing sexual assault (n=53). ⋯ The association of rs3800373, rs9380526, rs9394314, rs2817032, and rs2817040 with neck pain and/or overall pain 6 weeks after trauma was replicated in the sexual assault cohort, showing the same direction of the effect in each case. The results of this study indicate that genetic variants in FKBP5 influence the severity of musculoskeletal pain symptoms experienced during the weeks after motor vehicle collision and sexual assault. These results suggest that glucocorticoid pathways influence the development of persistent posttraumatic pain, and that such pathways may be a target of pharmacologic interventions aimed at improving recovery after trauma.
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Neurovascular coupling during nociceptive processing in the primary somatosensory cortex of the rat.
Neuroimaging methods such as functional magnetic resonance imaging (fMRI) have been used extensively to investigate pain-related cerebral mechanisms. However, these methods rely on a tight coupling of neuronal activity to hemodynamic changes. Because pain may be associated with hemodynamic changes unrelated to local neuronal activity (eg, increased mean arterial pressure [MAP]), it is essential to determine whether the neurovascular coupling is maintained during nociceptive processing. ⋯ However, when the stimulus intensity was kept constant, SI neurovascular coupling was not significantly affected by nociceptive counter-stimulation (P=0.4), which similarly affected the amplitude of shock-evoked LFP and CBF changes. It remains to be determined whether such neurovascular uncoupling occurs in humans, and whether it also affects other regions usually activated by painful stimuli. These results should be taken into account for accurate interpretation of fMRI studies that involve nociceptive stimuli associated with MAP changes.
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Migraine with aura is associated with an increased incidence of stroke and cardiovascular disease, but the biological mechanisms are poorly understood. This study examined the incidence of metabolic syndrome and its relationship to migraine with and without aura and to nonmigraine headache. In the population-based the Nord-Trøndelag Health Study (HUNT), 19,895 individuals were followed for the development of metabolic syndrome, with a median follow-up time of 11.3 years. ⋯ A moderate risk increase was seen for migraine without aura (IRR 1.26, 95% CI 1.12-1.42) and nonmigraine headache (IRR 1.22, 95% CI 1.13-1.32), not modified by smoking. The results suggest that traditional risk factors may be one of the mechanisms through which migraine with aura is linked to an increased risk for cardiovascular disease. A heightened vigilance concerning cardiovascular risk factors in this patient group may be warranted.
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Temporomandibular joint disorder (TMJD) is known for its mastication-associated pain. TMJD is medically relevant because of its prevalence, severity, chronicity, the therapy-refractoriness of its pain, and its largely elusive pathogenesis. Against this background, we sought to investigate the pathogenetic contributions of the calcium-permeable TRPV4 ion channel, robustly expressed in the trigeminal ganglion sensory neurons, to TMJ inflammation and pain behavior. ⋯ Mice with genetically-impaired MEK/ERK phosphorylation in neurons showed resistance to reduction of bite force similar to that of Trpv4(-/-) mice. Thus, TRPV4 is necessary for masticatory sensitization in TMJ inflammation and probably functions upstream of MEK/ERK phosphorylation in trigeminal ganglion sensory neurons in vivo. TRPV4 therefore represents a novel pronociceptive target in TMJ inflammation and should be considered a target of interest in human TMJD.