Peripherial Neuromodulation

Tyramine is a neuroactive compound that acts as neurotransmitter, neuromodulator, and neurohormone in insects. Three G protein-coupled receptors, TAR1-3, are responsible for mediating the intracellular pathway in the complex tyraminergic network. TAR1, the prominent player in this system, was initially classified as an octopamine receptor which can also be activated by tyramine, while it later appeared to be a true tyramine receptor. Even though TAR1 is currently considered as a well-defined tyramine receptor and several insect TAR1s have been characterized, a defined nomenclature is still inconsistent...

Arginine vasopressin (AVP) is a nonapeptide that serves as a neuromodulator in the brain and a hormone in the periphery that regulates water homeostasis and vasoconstriction. The subiculum is the major output region of the hippocampus and an integral component in the networks that processes sensory and motor cues to form a cognitive map encoding spatial, contextual, and emotional information. Whereas the subiculum expresses high densities of AVP-binding sites and AVP has been shown to increase the synaptic excitability of subicular pyramidal neurons, the underlying cellular and molecular mechanisms have not been determined...

Activation of V1a vasopressin receptors facilitates neuronal excitability in the medial nucleus of central amygdala (CeM) V1a receptor activation excites about 80% CeM neurons by opening a cationic conductance and about 20% CeM neurons by suppressing an inwardly rectifying K+ (Kir) channel The cationic conductance activated by V1a receptors is identified as TRPC5 channels PLCβ-mediated depletion of PIP2 is involved in V1a receptor-elicited excitation of CeM neurons Intracellular Ca2+ release and PKC are unnecessary for V1a receptor-mediated excitation of CeM neurons ABSTRACT: Arginine vasopressin (AVP) serves as a hormone in the periphery to modulate water homeostasis and a neuromodulator in the brain to regulate a diverse range of functions including anxiety, social behaviour, cognitive activities and nociception...

BACKGROUND: Pain is reported as the leading cause of disability in the common forms of inflammatory arthritis conditions. Acting as a key player in nociceptive processing, neuroinflammation, and neuron-glia communication, the chemokine CCL2/CCR2 axis holds great promise for controlling chronic painful arthritis. Here, we investigated how the CCL2/CCR2 system in the dorsal root ganglion (DRG) contributes to the peripheral inflammatory pain sensitization. METHODS: Repeated intrathecal (i...

In the peripheral neurons and circuits for hearing, balance, touch and pain, GABA plays diverse and important roles. In some cases, GABA is an essential player in the maintenance of sensory receptors and afferent neurons. In other instances, GABA modulates the sensory signal before it reaches CNS neurons. And in yet other instances, tonic GABA-mediated signals set the resting tone and excitability of afferent neurons. GABAA receptors are present on gustatory afferent neurons that carry taste signals from taste buds to central circuits in the brainstem...

Oxytocin (OXT) is a nonapeptide that serves as a neuromodulator in the brain and a hormone participating in parturition and lactation in the periphery. The subiculum is the major output region of the hippocampus and an integral component in the networks that process sensory and motor cues to form a cognitive map encoding spatial, contextual, and emotional information. Whilst the subiculum expresses the highest OXT-binding sites and is the first brain region to be activated by peripheral application of OXT, the precise actions of OXT in the subiculum have not been determined...

Objective. We aim at characterising the encoding of bladder pressure (intravesical pressure) by a population of sensory fibres. This research is motivated by the possibility to restore bladder function in elderly patients or after spinal cord injury using implanted devices, so called bioelectronic medicines. For these devices, nerve-based estimation of intravesical pressure can enable a personalized and on-demand stimulation paradigm, which has promise of being more effective and efficient. In this context, a better understanding of the encoding strategies employed by the body might in the future be exploited by informed decoding algorithms that enable a precise and robust bladder-pressure estimation...

The trigeminal nerve complex is a very important and somewhat unique component of the nervous system. It is responsible for the sensory signals that arise from the most part of the face, mouth, nose, meninges, and facial muscles, and also for the motor commands carried to the masticatory muscles. These signals travel through a very complex set of structures: dermal receptors, trigeminal branches, Gasserian ganglion, central nuclei, and thalamus, finally reaching the cerebral cortex. Other neural structures participate, directly or indirectly, in the transmission and modulation of the signals, especially the nociceptive ones; these include vagus nerve, sphenopalatine ganglion, occipital nerves, cervical spinal cord, periaqueductal gray matter, hypothalamus, and motor cortex...

BACKGROUND: Peripheral nerve stimulation (PNS) is a form of neuromodulation that is used to treat chronic and refractory neuropathic pain. Peripheral nerve stimulation was first described in the early 1960s when Shelden implanted a PNS device for trigeminal neuralgia. Despite PNS being known since the 1960s, technology designed specifically for PNS was lacking. Within the past few years, design-specific PNS devices have become widely available, with favorable efficacy and safety profiles...

In many species, vocal communication is essential for coordinating social behaviors including courtship, mating, parenting, rivalry, and alarm signaling. Effective communication requires accurate production, detection, and classification of signals, as well as selection of socially appropriate responses. Understanding how signals are generated and how acoustic signals are perceived is key to understanding the neurobiology of social behaviors. Here we review our long-standing research program focused on Xenopus , a frog genus which has provided valuable insights into the mechanisms and evolution of vertebrate social behaviors...

Cancer is a systemic disease. In order to fully understand it, we must take a holistic view on how cancer interacts with its host. The brain monitors and responds to natural and aberrant signals arriving from the periphery, particularly those of metabolic or immune origin. As has been well described, a hallmark of cancer is marked disruption of metabolic and inflammatory processes. Depending on the salience and timing of these inputs, the brain responds via neural and humoral routes to alter whole-body physiology...

Repellent odors are widely used to prevent insect-borne diseases, making it imperative to identify the conserved molecular underpinnings of their olfactory systems. Currently, little is known about the molecules supporting odor signaling beyond the odor receptors themselves. Most known molecules function in one of two classes of olfactory sensilla, single-walled or double-walled, which have differing morphology and odor response profiles. Here, we took two approaches to discover novel genes that contribute to insect olfaction in the periphery...

Innate behavioral biases and preferences can vary significantly among individuals of the same genotype. Though individuality is a fundamental property of behavior, it is not currently understood how individual differences in brain structure and physiology produce idiosyncratic behaviors. Here we present evidence for idiosyncrasy in olfactory behavior and neural responses in Drosophila We show that individual female Drosophila from a highly inbred laboratory strain exhibit idiosyncratic odor preferences that persist for days...

Neurotensin (NT) (pGlu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu) exerts a dual function as a neurotransmitter/neuromodulator in the central nervous system and as a hormone/cellular mediator in periphery. This dual function of NT establishes a connection between brain and peripheral tissues that renders this peptide a central player in energy homeostasis. Many biological actions of NT are mediated through its interaction with three types of NT receptors (NTS receptors). Despite its role in energy homeostasis, NT has a short half-life that hampers further determination of the biological actions of this peptide and its receptors in brain and periphery...

Acute and preventive treatment of primary headache disorders is not completely resolved with regards to efficacy, safety, and tolerability. Hence peripheral and central neuromodulation can provide therapeutic alternatives in drug-resistant cases. Peripheral targets of neuromodulation include invasive and non-invasive neurostimulation and electrical and chemical nerve and ganglion blockades. Areas covered: A PubMed search of papers published from January 2012 to October 2018 was conducted. The goal of this review was to analyze the efficacy and safety of invasive (implantable) peripheral neurostimulation methods (the occipital nerve, the cervical branch of vagal nerve, the sphenopalatine ganglion) and non-invasive (transcutaneous) peripheral neurostimulation methods (the occipital nerve, the supraorbital nerve, and the cervical and auricular branches of the vagal nerve), based on the results of published clinical trials and case series...

Widely used in industrialized countries, cannabis is a neuromodulator substance. The cannabinoid system is present at critical stages of retinal processing. We have recently shown a delay in bipolar and ganglion cell responses in regular cannabis users, as observed using flash (fERG) and pattern (PERG) electroretinogram. Although the results obtained during these tests provide information about global retinal responses, they do not give any indication about the spatial localization of the anomalies that were detected...

The dopaminergic system plays important roles in neuromodulation, such as motor control, motivation, reward, cognitive function, maternal, and reproductive behaviors. Dopamine is a neurotransmitter, synthesized in both central nervous system and the periphery, that exerts its actions upon binding to G protein-coupled receptors. Dopamine receptors are widely expressed in the body and function in both the peripheral and the central nervous systems. Dopaminergic signaling pathways are crucial to the maintenance of physiological processes and an unbalanced activity may lead to dysfunctions that are related to neurodegenerative diseases...

Substance P (SP) and neurotensin (NT) are neuropeptides isolated in the periphery and in the central nervous system. They are involved in various regulatory processes in the gastrointestinal tract, in the circulatory and respiratory systems, kidney and endocrine system. In addition to the peripheral effects, SP and NT act as neurotransmitters and neuromodulators in the central nervous system, regulating various behavioural actions, such as general and motor activity, pain, food and water intake, anxiety, reward/reinforcement and memory consolidation...

Neurotensin (NTS) has long been recognized as a neurotransmitter or neuromodulator in the central nervous system and as an endocrine agent in the periphery via actions mediated through neurotensin receptors (NTSRs). Many studies support a role for NTS in the endocrine, autocrine and paracrine growth stimulation of cancer, with oncogenic actions described for NTS in different types of cancers and cancer cell lines at each step of cancer progression, ranging from tumour growth and survival to metastatic spread...

Mammalian neurons that produce oxytocin and vasopressin apparently evolved from an ancient cell type with both sensory and neurosecretory properties that probably linked reproductive functions to energy status and feeding behavior. Oxytocin in modern mammals is an autocrine/paracrine regulator of cell function, a systemic hormone, a neuromodulator released from axon terminals within the brain, and a 'neurohormone' that acts at receptors distant from its site of release. In the periphery oxytocin is involved in electrolyte homeostasis, gastric motility, glucose homeostasis, adipogenesis, and osteogenesis, and within the brain it is involved in food reward, food choice, and satiety...