Neuroscience
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Studies using the flanker task have reported that response conflict is detected by the medial frontal cortex (MFC). As a conflict alert system, the MFC shows enhanced functional communication with task-related regions. Previous studies have revealed individual differences in functional connectivity during cognitive task performance. ⋯ However, these findings were only found in the right hemisphere, which may be related to the asymmetrical role of the bilateral PPC in response conflict processing. Furthermore, hierarchical regression analyses revealed that 44% of individual variability in FCz-P4 conflict-induced theta phase synchronization could be explained by variations in axial diffusivity (AD) in the genu of the corpus callosum (gCC). These results demonstrated that structural integrity in the gCC predicts conflict-induced functional connectivity between the MFC and right PPC.
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According to the theories of neural plasticity and neural efficiency, professional skill training improves performance by strengthening the underlying neural mechanisms. Therefore, subjects trained professionally may exhibit changes in resting-state neurophysiological characteristics closely related to performance. ⋯ There was also a significant linear correlation between the characteristic path length of the resting-state theta band brain network and shooting performance (r = 0.56, P < 0.0005). This study identifies potential neural mechanisms underlying successful shooting and a new method for predicting and evaluating performance based on EEG characteristics.
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The calcium-binding protein, parvalbumin (PV), is highly expressed in thalamic reticular nucleus (TRN) GABAergic neurons, which receive input from the cerebral cortex and thalamus and send inhibitory output to the thalamic relay nucleus. Previous studies suggest that the TRN is involved in pain regulation as an important relay nucleus of the ascending pain pathway. However, little is known about its functional role in pain regulation and interconnectivity. ⋯ Furthermore, the anterodorsal and paratenial thalamic nucleus received innervation from PV-positive neurons in the TRNrd. They were specifically inhibited by GABA, which is released from local axonal endings of PV neurons. These findings indicate that activation of PV neurons in the TRNrd increases pain sensitivity in PV-Cre transgenic mice.
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Repeated use of opioids can lead to the development of analgesic tolerance and dependence. Additionally, chronic opioid exposure can cause a paradoxical emergence of heightened pain sensitivity to noxious stimuli, termed hyperalgesia, which may drive continued or escalated use of opioids to manage worsening pain symptoms. Opioid-induced hyperalgesia has traditionally been measured in rodents via reflex-based assays, including the von Frey method. ⋯ We next investigated individual relationships between pain avoidance-like behavior and alterations in protein phosphorylation in central motivation-related brain areas. We discovered that pain avoidance-like behavior was significantly correlated with alterations in phosphorylation status of protein kinases (ERK, CaMKII), transcription factors (CREB), presynaptic markers of neurotransmitter release (Synapsin), and the rate-limiting enzyme for dopamine synthesis (TH) across specific brain regions. Our findings suggest that alterations in phosphorylation events in specific brain centers may support cognitive/motivational responses to avoid pain.
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Although inflammation-induced peripheral sensitization oftentimes resolves as an injury heals, this sensitization can be pathologically maintained and contribute to chronic inflammatory pain. Numerous inflammatory mediators increase the production of reactive oxygen (ROS) and nitrogen species (RNS) during inflammation and in animal models of chronic neuropathic pain. Our previous studies demonstrate that ROS/RNS and subsequent DNA damage mediate changes in neuronal sensitivity induced by anticancer drugs and by ionizing radiation in sensory neurons, thus we investigated whether inflammation and inflammatory mediators also could cause DNA damage in sensory neurons and whether that DNA damage alters neuronal sensitivity. ⋯ Genetically enhancing the expression of the DNA repair enzyme, apurinic/apyrimidinic endonuclease (APE1) or treatment with a small-molecule modulator of APE1 DNA repair activity, both which enhance DNA repair, attenuated DNA damage and the changes in neuronal sensitivity elicited by LPS or MCP-1. In conclusion, our studies demonstrate that inflammation or exposure to inflammatory mediators elicits DNA damage in sensory neurons. By enhancing DNA repair, we demonstrate that this DNA damage mediates the alteration of neuronal function induced by inflammatory mediators in peptidergic sensory neurons.