Brain inflammation: the case of CGRP
The central nervous system was thought to be an immune-privileged organ: the view is changing and it is now referred to as immune-specialized. Moreover, brain inflammation is recognized to cause not only severe neuroinflammatory diseases such as multiple sclerosis, but also to be underlying in classic neurodegenerative diseases as Parkinson's and Alzheimer's disease. The main brain immune effector cells are microglia that are considered to be general homeostatic guardians of the central nervous system. (Source: Neuropeptides)
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: Stefano Morara Source Type: research
Evaluation of the CGRP Neutralizing Antibody LY2951742 for the Treatment of Migraine and Osteoarthritis Pain
Calcitonin gene-related peptide (CGRP) is a potent vasodilator, but also has well established roles in neurogenic inflammation and nociception. Multiple pieces of evidence support the role of CGRP in migraine including the elevated plasma CGRP levels during migraine attacks, the induction of migraine attacks by CGRP infusion and the clinical efficacy of CGRP receptor antagonists and CGRP antibodies. The role of CGRP in osteoarthritis (OA) pain has been suggested by studies showing increased expression of CGRP containing nerves in painful OA joints, increased CGRP levels in the plasma and synovial fluid of OA patients and t...
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: Kirk Johnson, Vladimir Skljarevski, Qi Zhang, Margaret Ferguson, Tina Oakes, James Martinez, David Monteith, Yan Jin, Claire Smith, Mark Chambers, Miles Siegel, Robert Benschop, Aaron Schacht Source Type: research
Exploring genetic and epigenetic variation of the cannabinoid receptor-1 gene; implications for personalised medicine
Personalised medicine represents one of the key goals of medicine. In addition to influencing disease susceptibility, it is highly likely that genetic and epigenetic variation also cause significant variation in drug efficacy and side effects within patient groups. Less than 10% of genetic variants associated with disease are in gene coding regions. Therefore, we examined the possible roles of variations in gene regulatory regions that may enable prediction of disease susceptibility and improve drug response stratification. (Source: Neuropeptides)
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: Elizabeth Hay, Philip Cowie, Roger Pertwee, Alasdair MacKenzie Source Type: research
Inhibition of Joint Neuroinflammation by the Endocannabinoid System
Background: Antidromic stimulation of knee joint primary afferents has previously been shown to increase synovial blood flow and promote vascular extravasation. These neurogenically-mediated pro-inflammatory effects are orchestrated by sensory neuropeptides. Endocannabinoids have been shown to ameliorate acute synovitis in rodent knees; however, their role in modulating neurogenic inflammation is unknown. (Source: Neuropeptides)
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: Jason McDougall, Milind Muley, Eugene Krustev Source Type: research
Mediator role of the Transient Receptor Potential Ankyrin 1 (TRPA1) receptor in chronic arthritis
The Transient Receptor Potential Ankyrin 1 (TRPA1) cation channel is expressed on capsaisin-sensitive sensory neurons, endothelial and inflammatory cells, and stimulated by a variety of inflammatory mediators. Since few contradictory data are available about its role in arthritis and related pain, we investigated its involvement in inflammation models of different mechanisms. (Source: Neuropeptides)
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: Ádám Horváth, Valéria Tékus, Melinda Boros, Gábor Pozsgai, Bálint Botz, Éva Borbély, János Szolcsányi, Erika Pintér, Zsuzsanna Helyes Source Type: research
C-Tactile Afferents: The mediators of oxytocin release during affiliative interaction?
Low intensity, non-noxious, stimulation of cutaneous somatosensory nerves has been shown to trigger oxytocin release and is associated with increased social motivation, plus reduced physiological and behavioural reactivity to stressors. However to date, little attention has been paid to the specific nature of the mechanosensory nerves which mediate these effects. In recent years, the neuroscientific study of human skin nerves (microneurography studies on single peripheral nerve fibers) has led to the identification and characterisation of a class of touch sensitive nerve fibres named C-Tactile afferents (CTs). (Source: Neuropeptides)
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: Susannah Walker, Francis McGlone Source Type: research
Assessing the role of the oxytocinergic system in social and general anxiety
The neuropeptide oxytocin (OXT) has been revealed as a profound anxiolytic and anti-stress factor of the brain, besides its many prosocial and reproductive effects. Therefore, there is substantial scientific and medical interest in its potential therapeutic use for the treatment of psychopathologies associated with anxiety, fear, and social dysfunctions, such as generalized anxiety disorder, posttraumatic stress disorder, and social anxiety disorder, as well as autism and schizophrenia, among others. (Source: Neuropeptides)
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: David Slattery Source Type: research
Challenges of neuropeptide based drug discovery and development
There are a wide range of neuropeptide systems that are of significant interest as drug targets for a similarly wide range of therapeutic rationales. These range from oncology, through diabetes, drug abuse and migraine to psychiatry. Most of the drug discovery efforts against the various targets have adopted a peptidomimetic approach. These efforts have proved difficult not only from the drug identification perspective, but with stability and delivery to target also being major issues have rarely yielded marketable products. (Source: Neuropeptides)
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: Hugh Marston, Keith Wafford Source Type: research
Morphine dependence is associated with changes in neuropeptide S receptor expression and function in the rat brain
University of Camerino, Camerino, (MC), Italy (Source: Neuropeptides)
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Source Type: research
Angiotensin II as a trophic factor mediating sensory axon sprouting and hypersensitivity in inflammatory pain
Inflammation is often accompanied by persistent hypersensitivity, and studies in humans and animals show abnormally increased sensory innervation density. We showed previously that dorsal root ganglion (DRG) neurons express angiotensin II (ANGII) AT2 receptors that mediate axon sprouting. Using overexpression we show that AT2 levels determine the extent of axon outgrowth, and we have dissected the local inflammatory renin-angiotensin system (RAS) to better understand its role in inflammatory hyperinnervation. (Source: Neuropeptides)
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: Peter Smith, Anuradha Chakrabarty, Ying Mu, Aritra Bhattacherjee, Zhaohui Liao Source Type: research
Neurokinin Receptor Coupling and Nociceptive Processing
Substance P (SP) has long been implicated in the neuronal processes that underlie pain processing and perception, originally based on its selective expression in peripheral nociceptors. Several types of G-protein coupled receptors (GPCR) can be activated by SP, but its role in pain signaling has largely been associated with its activation of the neurokinin-1 receptor (NK-1). The plasticity of expression and coupling of GPCRs is relatively well defined in some (e.g., beta adrenergic) receptor systems, but the role of NK-1 plasticity in dynamics of pain sensitization is not well understood. (Source: Neuropeptides)
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: Kenneth McCarson Source Type: research
Hemokinin-1 plays a potent pronociceptive role in acute and chronic models in mice
The Tac1 gene-encoded Substance P (SP) acting at the tachykinin NK1 receptor is involved in different pain states, but NK1 antagonists failed in clinical trials. The Tac4 gene-derived hemokinin-1 (HK-1) is present in pain-related brain regions and also activates the NK1 receptor with binding site and signaling pathways different from SP, but other mechanisms of action have been proposed. We investigated its involvement in pain conditions of distinct mechanisms in C57Bl/6 wildtype (WT), Tac4 and NK1 gene-deleted (Tac4-/-; NK1-/-) mice. (Source: Neuropeptides)
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: Eva Borbely, Zsofia Hajna, Balint Scheich, Agnes Hunyady, Katinka Bekefi, Timea Gubanyi, Alexandra Berger, Christopher J Paige, Jason McDougall, John Quinn, Janos Szolcsanyi, Erika Pinter, Zsuzsanna Helyes Source Type: research
Analysis of expression of SP and NOS in the porcine nodose ganglion (NG) sensory neurons supplying prepyloric stomach region after intragastric hydrochloric acid infusion
We analyzed expression of substance P (SP) and nitric oxide synthase (nNOS) in the porcine nodose ganglion sensory neurons innervating prepyloric stomach region in physiological state and following intragastric infusion of hydrochloric acid. (Source: Neuropeptides)
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: Liliana Rytel, Jaroslaw Calka Source Type: research
The Neuropeptide Concept: lessons from fifty years ago …
In 1969 David de Wied launched his neuropeptide concept. Lesions of the pituitary resulted in diminished conditioned avoidance behavior: lesions of the anterior pituitary affected acquisition while posterior lesions facilitated extinction. Injections of the neuropeptides ACTH and vasopressin restored these functions. De Wied concluded that these neuropeptides have, in addition to their endocrine effects, direct effects in the brain, specifically on learning and memory. He met quite a lot of criticism.- The mechanisms of action and how neuropeptides reach the relevant brain sites were completely unknown then. (Source: Neuropeptides)
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: Berry M. Spruijt Source Type: research
Using animals selectively bred for high and low trait anxiety to investigate the role of Neuropeptide S in anxiety disorders
Neuropeptide S (NPS) has generated substantial interest due to its anxiolytic and fear-attenuating effects in rodents, while a corresponding receptor polymorphism associated with increased NPS receptor (NPSR1) surface expression and efficacy has been implicated in an increased risk of panic disorder in humans. To gain insight into this paradox, we examined the NPS system in rats and mice bred for high anxiety-related behaviour (HAB) versus low anxiety-related behaviour, and, thereafter, determined the effect of central NPS administration on anxiety- and fear-related behaviour. (Source: Neuropeptides)
Source: Neuropeptides - October 1, 2017 Category: Neuroscience Authors: David Slattery Source Type: research
