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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Limb amputation may lead to chronic painful sensations referred to the absent limb, ie phantom limb pain (PLP), which is likely subtended by maladaptive plasticity. The present study investigated whether transcranial direct current stimulation (tDCS), a noninvasive technique of brain stimulation that can modulate neuroplasticity, can reduce PLP. In 2 double-blind, sham-controlled experiments in subjects with unilateral lower or upper limb amputation, we measured the effects of a single session of tDCS (2 mA, 15 min) of the primary motor cortex (M1) and of the posterior parietal cortex (PPC) on PLP, stump pain, nonpainful phantom limb sensations and telescoping. ⋯ PLP is associated primarily with cortical excitability shifts in the sensorimotor network; increasing excitability in this system by anodal tDCS has an antalgic effect on PLP. Conversely, nonpainful phantom sensations are associated to a hyperexcitation of PPC that can be normalized by cathodal tDCS. This evidence highlights the relationship between the level of excitability of different cortical areas, which underpins maladaptive plasticity following limb amputation and the phenomenology of phantom limb, and it opens up new opportunities for the use of tDCS in the treatment of PLP.
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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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Voltage-gated Na(+) channels (Nav) are the targets of a variety of scorpion toxins. Here, we investigated the effects of Amm VIII, a toxin isolated from the venom of the scorpion Androctonus mauretanicus mauretanicus, on pain-related behaviours in mice. The effects of Amm VIII were compared with the classic scorpion α-toxin AaH II from Androctonus australis. ⋯ AaH II and Amm VIII reduced first spike latency and lowered action potential threshold. Amm VIII was less efficient than AaH II in increasing the gain of the firing frequency-stimulation relationship. In conclusion, our data show that Amm VIII, although less potent than AaH II, acts as a gating-modifier peptide reminiscent of classic α-toxins, and suggest that its hyperalgesic effects can be ascribed to gain-of-function of TTX-S Na(+) channels in nociceptors.