Pflügers Archiv : European journal of physiology
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Small (<25 microm in diameter) neurons of the dorsal root ganglion (DRG) express multiple voltage-gated Na(+) channel subtypes, two of which being resistant to tetrodotoxin (TTX). Each subtype mediates Na(+) current with distinct kinetic property. However, it is not known how each type of Na(+) channel contributes to the generation of action potentials in small DRG neurons. ⋯ We also confirmed that TTX-R/persistent Na(+) current mediated by Na(V)1.9 actually regulates subthreshold excitability in small DRG neurons. In addition, we demon strated that TTX-R/persistent Na(+) current can carry an action potential when the amplitude of this current was abnormally increased. Thus, our results indicate that the action potentials in small DRG neurons are generated and regulated with a combination of multiple mechanisms that may give rise to unique functional properties of small DRG neurons.
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We identified major subunits of the nicotinic acetylcholine receptor (nAChR) involved in excitatory postsynaptic potential and intracellular Ca(2+) ([Ca(2+)]i) increase in the major pelvic ganglion (MPG) neurons of the male rat. ACh elicited fast inward currents in both sympathetic and parasympathetic MPG neurons. Mecamylamine, a selective antagonist for alpha3beta4 nAChR, potently inhibited the ACh-induced currents in sympathetic and parasympathetic neurons (IC(50); 0.53 and 0.22 microM, respectively). ⋯ ACh-induced [Ca(2+)]i increase was blocked by mecamylamine (10 microM), but was not affected by atropine (1 microM). RT-PCR analysis showed that, among subunits of nAChR, alpha3 and beta4 were predominantly expressed in MPG. We suggest that activation of alpha3 and beta4 nAChR subunits in MPG neurons induce fast inward currents and [Ca(2+)]i increase, possibly mediating a major role in pelvic autonomic synaptic transmission.
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Emerging evidence indicates that microglia play a critical role in the pathogenesis of neuropathic pain, a debilitating chronic pain condition that can occur after peripheral nerve damage caused by disease, infection, or physical injury. Microglia are immunocompetent cells of the central nervous system and express various ionotropic P2X and metabotropic P2Y purinoceptors. ⋯ Recent findings suggest that activation of P2X4 receptors evokes release of brain-derived neurotrophic factor from microglia and that this mediates microglia-neuron signaling leading to pain hypersensitivity. Thus, P2X4 receptors and the intracellular signaling mediators in microglia are promising therapeutic targets for the development of novel pharmacological agents in the management of neuropathic pain.
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Randomized Controlled Trial
Transient cold pain has no effect on cutaneous vasodilatation induced by capsaicin: a randomized-control-crossover study in healthy subjects.
Cooling the skin induces sympathetically driven vasoconstriction, along with some vasoparalytic dilatation at lowermost temperatures. Neurogenic inflammation, on the other hand, entails vasodilatation. In the present study, we examined the dynamic vasomotor balance of capsaicin-induced vasodilatation within the area of the induced neurogenic inflammation, with and without superimposed cooling. ⋯ Two-way repeated-measures ANOVA indicated no interaction between the experimental conditions (capsaicin with or without cold) and time (F=0.934, p=0.454). The cold pain stimulation was found to be insignificant in its influence on BF evoked by capsaicin (F=0.018, p=0.894). The results of our study indicate that (1) transient cooling causes significant vasodilatation, (2) intradermal injection of capsaicin is dominant in inducing vasodilatation, and (3) the cold-pain-evoked vasodilatation has no modulative effect on the capsaicin-evoked cutaneous vasodilatation.
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Electrical excitability, which plays an important role in excitation-contraction coupling in the pulmonary vasculature, is regulated by transmembrane ion flux in pulmonary artery smooth muscle cells (PASMC). This study aimed to characterize the electrophysiological properties and molecular identities of voltage-gated Na(+) channels in cultured human PASMC. We recorded tetrodotoxin (TTX) sensitive and rapidly inactivating Na(+) currents with properties similar to those described in cardiac myocytes. ⋯ Our results demonstrate that human PASMC express TTX-sensitive voltage-gated Na(+) channels. Their physiological functions remain unresolved, although our data suggest that Na(+) channel activity does not directly influence membrane potential, intracellular Ca(2+) release, or proliferation in normal human PASMC. Whether their expression and/or activity are heightened in the pathological state is discussed.