Articles: nav1-8-voltage-gated-sodium-channel-metabolism.
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Opiates are powerful drugs to treat severe pain, and act via mu opioid receptors distributed throughout the nervous system. Their clinical use is hampered by centrally-mediated adverse effects, including nausea or respiratory depression. Here we used a genetic approach to investigate the potential of peripheral mu opioid receptors as targets for pain treatment. ⋯ We therefore genetically demonstrate for the first time that mu opioid receptors partly mediate opiate analgesia at the level of Nav1.8-positive sensory neurons. In our study, this mechanism operates under conditions of inflammatory pain, but not nociception. Previous pharmacology suggests that peripheral opiates may be clinically useful, and our data further demonstrate that Nav1.8 neuron-associated mu opioid receptors are feasible targets to alleviate some forms of persistent pain.
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A vast diversity of salient cues is sensed by numerous classes of primary sensory neurons, defined by specific neuropeptides, ion channels, or cytoskeletal proteins. Recent evidence has demonstrated a correlation between the expression of some of these molecular markers and transmission of signals related to distinct sensory modalities (eg, heat, cold, pressure). Voltage-gated sodium channel Na(v)1.8 has been reported to be preferentially expressed in small-diameter unmyelinated sensory afferents specialized for the detection of noxious stimuli (nociceptors), and Na(v)1.8-Cre mice have been widely used to investigate gene function in nociceptors. ⋯ We demonstrate that 75% of dorsal root ganglion (DRG) neurons express Na(v)1.8-Cre, including >90% of neurons expressing markers of nociceptors and, unexpectedly, a large population (∼40%) of neurons with myelinated A fibers. Furthermore, analysis of DRG neurons' central and peripheral projections revealed that Na(v)1.8-Cre is not restricted to nociceptors but is also expressed by at least 2 types of low-threshold mechanoreceptors essential for touch sensation, including those with C and Aβ fibers. Our results indicate that Na(v)1.8 underlies electrical activity of sensory neurons subserving multiple functional modalities, and call for cautious interpretation of the phenotypes of Na(v)1.8-Cre-driven conditional knockout mice.
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Comparative Study
NaV 1.8, but not NaV 1.9, is upregulated in the inflamed dental pulp tissue of human primary teeth.
To investigate alterations in Na(V) 1.8 and Na(V) 1.9 expression within inflamed dental pulp tissue of human primary teeth. ⋯ Na(V) 1.8 alone may be the therapeutic target for treatment of painful pulpitis in primary teeth.
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To investigate the relationship between dental pain and Nav1.8 expression level by detecting the expression of voltage-gated sodium channel Nav1.8 in normal human dental pulps and painful pulp tissues. ⋯ The expression level of Nav1.8 increased significantly in painful dental pulp tissue, suggesting that Nav1.8 may play an important role in the development and transmission of dental pain.