Human Stem Cell-Derived TRPV1-Positive Sensory Neurons: A New Tool to Study Mechanisms of Sensitization.

Somatosensation, the detection and transduction of external and internal stimuli such as temperature or mechanical force, is vital to sustaining our bodily integrity. But still, some of the mechanisms of distinct stimuli detection and transduction are not entirely understood, especially when noxious perception turns into chronic pain. Over the past decade major progress has increased our understanding in areas such as mechanotransduction or sensory neuron classification.

Human vs. Mouse Nociceptors - Similarities and Differences.

The somatosensory system allows us to detect a diverse range of physical and chemical stimuli including noxious ones, which can initiate protective reflexes to prevent tissue damage. However, the sensation of pain can - under pathological circumstances - outlive its usefulness and perpetrate ongoing suffering. Rodent model systems have been tremendously useful to help understand basic mechanisms of pain perception.

Protein Kinase C Epsilon Activity in the Nucleus Accumbens and Central Nucleus of the Amygdala Mediates Binge Alcohol Consumption.

Background: Protein kinase C epsilon (PKCε) is emerging as a potential target for the development of pharmacotherapies to treat alcohol use disorders, yet little is known regarding how a history of a highly prevalent form of drinking, binge alcohol intake, influences enzyme priming or the functional relevance of kinase activity for excessive alcohol intake.

Methods: Immunoblotting was employed on tissue from subregions of the nucleus accumbens (NAc) and the amygdala to examine both idiopathic and binge drinking-induced changes in constitutive PKCε priming. The functional relevance of PKCε translocation for binge drinking and determination of potential upstream signaling pathways involved were investigated using neuropharmacologic approaches within the context of two distinct binge drinking procedures, drinking in the dark and scheduled high alcohol consumption.

PIEZO2 is required for mechanotransduction in human stem cell-derived touch receptors.

Human sensory neurons are inaccessible for functional examination, and thus little is known about the mechanisms mediating touch sensation in humans. Here we demonstrate that the mechanosensitivity of human embryonic stem (hES) cell-derived touch receptors depends on PIEZO2. To recapitulate sensory neuron development in vitro, we established a multistep differentiation protocol and generated sensory neurons via the intermediate production of neural crest cells derived from hES cells or human induced pluripotent stem (hiPS) cells.

mGluR1 within the nucleus accumbens regulates alcohol intake in mice under limited-access conditions.

Idiopathic or alcohol-induced increases in the expression and function of the Group1 metabotropic glutamate receptor subtype 1 (mGluR1) within the extended amygdala are theorized to contribute to an individual's propensity to consume excessive amounts of alcohol. In the past, the detailed study of the functional relevance of mGluR1 for alcoholism-related behaviors in animal models was hampered by the poor solubility and non-specific side effects of available inhibitors; however, the advent of the highly potent and soluble mGluR1 negative allosteric modulator JNJ-16259685 [(3,4-Dihydro-2H-pyrano[2,3-b]quinolin-7-yl)-(cis-4-methoxycyclohexyl)-methanone] has instigated a re-examination of the role for this mGluR subtype in mediating the behavioral effects of alcohol. In this regard, systemic pretreatment with JNJ-16259685 was proven effective at reducing alcohol reinforcement and motivation for the drug.