The integration of somatosensory information is generally assumed to be a function of the central nervous system (CNS). Here we describe fully functional GABAergic communication within rodent peripheral sensory ganglia and show that it can modulate transmission of pain-related signals from the peripheral sensory nerves to the CNS. We found that sensory neurons express major proteins necessary for GABA synthesis and release and that sensory neurons released GABA in response to depolarization. In vivo focal infusion of GABA or GABA reuptake inhibitor to sensory ganglia dramatically reduced acute peripherally induced nociception and alleviated neuropathic and inflammatory pain. In addition, focal application of GABA receptor antagonists to sensory ganglia triggered or exacerbated peripherally induced nociception. We also demonstrated that chemogenetic or optogenetic depolarization of GABAergic dorsal root ganglion neurons in vivo reduced acute and chronic peripherally induced nociception. Mechanistically, GABA depolarized the majority of sensory neuron somata, yet produced a net inhibitory effect on the nociceptive transmission due to the filtering effect at nociceptive fiber T-junctions. Our findings indicate that peripheral somatosensory ganglia represent a hitherto underappreciated site of somatosensory signal integration and offer a potential target for therapeutic intervention.
In this work the ion-selective response of an electrolyte-gated carbon-nanotube field-effect transistor (CNT-FET) towards K(+), Ca(2+) and Cl(-) in the biologically relevant concentration range from 10(-1) M to 10(-6) M is demonstrated. The ion-selective response is achieved by modifying the gate-electrode of an electrolyte-gated CNT-FET with ion-selective membranes, which are selective towards the respective target analyte ions. The selectivity, assured by the ion-selective poly(vinyl chloride) based membrane, allows the successful application of the herein proposed K(+)-selective CNT-FET to detect changes in the K(+) activity in the μM range even in solutions containing different ionic backgrounds. The sensing mechanism relies on a superposition of both an ion-sensitive response of the CNT-network as well as a change of the effective gate potential present at the semiconducting channel due to a selective and ion activity-dependent response of the membrane towards different types of ions. Moreover, the combination of a CNT-FET as a transducing element gated with an ion-selective coated-wire electrode offers the possibility to miniaturize the already well-established conventional ion-selective electrode setup. This approach represents a valuable strategy for the realization of portable, multi-purpose and low-cost biosensing devices.
An experimental approach allowing visualization and quantification of the underestimated spontaneous process of partition of conducting polymer transducer material to the ion-selective membrane phase is proposed. The approach proposed is based on optical properties of the transducer material applied, using polythiophene as a model system. It is shown that this process occurs not only during the sensor preparation step but also during pretreatment of the sensor before use. As shown, this uncontrolled partition of the transducer to the receptor leads to conducting polymer contents in the membrane phase reaching 0.5% w/w; this process is accompanied by a partial spontaneous change of the oxidation state of polythiophene. The conducting polymer present in the membrane participates to some extent in the overall response of the sensor, which can be observed as a change in the polythiophene optical emission spectra. Fluorescence microscopic images obtained clearly show that the conducting polymer is distributed throughout the membrane thickness, being present also at the membrane/solution interface. The experimental results presented were obtained for K-selective sensors using poly(3-octylthiophene) as a model transducer; however, the proposed approach is also applicable for other systems.
The effect of platinum nanoparticles introduction into polyacrylate membranes was examined. Platinum nanoparticles were added to the membrane cocktail before photopolymerization of the poly(n-butyl acrylate) based ion-selective membranes. Thus obtained sensors were characterized with significantly lowered electrical resistance and increased stability of potential readings compared to classical poly(n-butyl acrylate) membranes. The analytical parameters of platinum nanoparticle containing membranes were well comparable with those of classical membranes.
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