Neural Mechanisms of Itch

2020 ◽  
Vol 43 (1) ◽  
pp. 187-205 ◽  
Author(s):  
Mark Lay ◽  
Xinzhong Dong
Keyword(s):  
Spinal Cord ◽  
Immune Response ◽  
Neural Mechanisms ◽  
Mechanical Stimuli ◽  
External Threats ◽  
Brain Circuits ◽  
Cross Modulation ◽  
Itch Sensation ◽  
Neuron Terminals ◽  
The Brain

Itch is a unique sensation that helps organisms scratch away external threats; scratching itself induces an immune response that can contribute to more itchiness. Itch is induced chemically in the peripheral nervous system via a wide array of receptors. Given the superficial localization of itch neuron terminals, cells that dwell close to the skin contribute significantly to itch. Certain mechanical stimuli mediated by recently discovered circuits also contribute to the itch sensation. Ultimately, in the spinal cord, and likely in the brain, circuits that mediate touch, pain, and itch engage in cross modulation. Much of itch perception is still a mystery, but we present in this review the known ligands and receptors associated with itch. We also describe experiments and findings from investigations into the spinal and supraspinal circuitry responsible for the sensation of itch.

scholarly journals Pain Inhibits GRPR Neurons via GABAergic Signaling in the Spinal Cord

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Rita Bardoni ◽  
Kai-Feng Shen ◽  
Hui Li ◽  
Joseph Jeffry ◽  
Devin M. Barry ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neural Mechanisms ◽  
Projection Neurons ◽  
Spinal Neurons ◽  
Peptide Receptor ◽  
Gastrin Releasing Peptide ◽  
Spinal Mechanism ◽  
Itch Sensation ◽  
Neurokinin 1

Abstract It has been known that algogens and cooling could inhibit itch sensation; however, the underlying molecular and neural mechanisms remain poorly understood. Here, we show that the spinal neurons expressing gastrin releasing peptide receptor (GRPR) primarily comprise excitatory interneurons that receive direct and indirect inputs from C and Aδ fibers and form contacts with projection neurons expressing the neurokinin 1 receptor (NK1R). Importantly, we show that noxious or cooling agents inhibit the activity of GRPR neurons via GABAergic signaling. By contrast, capsaicin, which evokes a mix of itch and pain sensations, enhances both excitatory and inhibitory spontaneous synaptic transmission onto GRPR neurons. These data strengthen the role of GRPR neurons as a key circuit for itch transmission and illustrate a spinal mechanism whereby pain inhibits itch by suppressing the function of GRPR neurons.

scholarly journals Differential expression of multiple kallikreins in a viral model of multiple sclerosis points to unique roles in the innate and adaptive immune response

2014 ◽  
Vol 395 (9) ◽  
pp. 1063-1073 ◽  
Author(s):  
Michael Panos ◽  
George P. Christophi ◽  
Moses Rodriguez ◽  
Isobel A. Scarisbrick
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Immune Response ◽  
Demyelinating Disease ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Axon Degeneration ◽  
Functional Link ◽  
The Brain

Abstract Recent studies provide a functional link between kallikrein 6 (Klk6) and the development and progression of disease in patients with multiple sclerosis (MS) and in its murine models. To evaluate the involvement of additional kallikrein family members, we compared Klk6 expression with four other kallikreins (Klk1, Klk7, Klk8, and Klk10) in the brain and spinal cord of mice infected with Theiler’s murine encephalomyelitis virus, an experimental model of progressive MS. The robust upregulation of Klk6 and Klk8 in the brain during the acute phase of viral encephalitis and in the spinal cord during disease development and progression points to their participation in inflammation, demyelination, and progressive axon degeneration. More limited changes in Klk1, Klk7, and Klk10 were also observed. In addition, Klk1, Klk6, and Klk10 were dynamically regulated in T cells in vitro as a recall response to viral antigen and in activated monocytes, pointing to their activities in the development of adaptive and innate immune function. Together, these results point to overlapping and unique roles for multiple kallikreins in the development and progression of virus-mediated central nervous system inflammatory demyelinating disease, including activities in the development of the adaptive and innate immune response, in demyelination, and in progressive axon degeneration.

scholarly journals How Reward and Aversion Shape Motivation and Decision Making: A Computational Account

2019 ◽  
Vol 26 (1) ◽  
pp. 87-99 ◽  
Author(s):  
Jeroen P. H. Verharen ◽  
Roger A. H. Adan ◽  
Louk J. M. J. Vanderschuren
Keyword(s):  
Decision Making ◽  
Substance Use ◽  
Neural Mechanisms ◽  
Behavioral Adaptation ◽  
Costs And Benefits ◽  
Substance Addiction ◽  
The Core ◽  
Brain Circuits ◽  
Motivated Behaviors ◽  
The Brain

Processing rewarding and aversive signals lies at the core of many adaptive behaviors, including value-based decision making. The brain circuits processing these signals are widespread and include the prefrontal cortex, amygdala and striatum, and their dopaminergic innervation. In this review, we integrate historic findings on the behavioral and neural mechanisms of value-based decision making with recent, groundbreaking work in this area. On the basis of this integrated view, we discuss a neuroeconomic framework of value-based decision making, use this to explain the motivation to pursue rewards and how motivation relates to the costs and benefits associated with different courses of action. As such, we consider substance addiction and overeating as states of altered value-based decision making, in which the expectation of reward chronically outweighs the costs associated with substance use and food consumption, respectively. Together, this review aims to provide a concise and accessible overview of important literature on the neural mechanisms of behavioral adaptation to reward and aversion and how these mediate motivated behaviors.

Inhibition of Hsp90 in the spinal cord enhances the antinociceptive effects of morphine by activating an ERK-RSK pathway

2020 ◽  
Vol 13 (630) ◽  
pp. eaaz1854
Author(s):  
David I. Duron ◽  
Wei Lei ◽  
Natalie K. Barker ◽  
Carrie Stine ◽  
Sanket Mishra ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Side Effects ◽  
Opioid Therapy ◽  
Mechanical Stimuli ◽  
Hsp90 Inhibition ◽  
Chaperone Protein ◽  
Dorsal Horns ◽  
Antinociceptive Effects ◽  
Μ Opioid Receptor ◽  
The Brain

Morphine and other opioids are commonly used to treat pain despite their numerous adverse side effects. Modulating μ-opioid receptor (MOR) signaling is one way to potentially improve opioid therapy. In mice, the chaperone protein Hsp90 mediates MOR signaling within the brain. Here, we found that inhibiting Hsp90 specifically in the spinal cord enhanced the antinociceptive effects of morphine in mice. Intrathecal, but not systemic, administration of the Hsp90 inhibitors 17-AAG or KU-32 amplified the effects of morphine in suppressing sensitivity to both thermal and mechanical stimuli in mice. Hsp90 inhibition enabled opioid-induced phosphorylation of the kinase ERK and increased abundance of the kinase RSK in the dorsal horns of the spinal cord, which are heavily populated with primary afferent sensory neurons. The additive effects of Hsp90 inhibition were abolished upon intrathecal inhibition of ERK, RSK, or protein synthesis. This mechanism downstream of MOR, localized to the spinal cord and repressed by Hsp90, may potentially be used to enhance the efficacy and presumably decrease the side effects of opioid therapy.

Central Nerve System Impairment, AMA Guides, Sixth Edition: An Overview

2018 ◽  
Vol 23 (1) ◽  
pp. 10-13
Author(s):  
James B. Talmage ◽  
Jay Blaisdell
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Neurological Impairment ◽  
Sixth Edition ◽  
Central Nerve System ◽  
The Central Nervous System ◽  
The One ◽  
Nerve System ◽  
The Brain

Abstract Injuries that affect the central nervous system (CNS) can be catastrophic because they involve the brain or spinal cord, and determining the underlying clinical cause of impairment is essential in using the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), in part because the AMA Guides addresses neurological impairment in several chapters. Unlike the musculoskeletal chapters, Chapter 13, The Central and Peripheral Nervous System, does not use grades, grade modifiers, and a net adjustment formula; rather the chapter uses an approach that is similar to that in prior editions of the AMA Guides. The following steps can be used to perform a CNS rating: 1) evaluate all four major categories of cerebral impairment, and choose the one that is most severe; 2) rate the single most severe cerebral impairment of the four major categories; 3) rate all other impairments that are due to neurogenic problems; and 4) combine the rating of the single most severe category of cerebral impairment with the ratings of all other impairments. Because some neurological dysfunctions are rated elsewhere in the AMA Guides, Sixth Edition, the evaluator may consult Table 13-1 to verify the appropriate chapter to use.

scholarly journals Efficacy of Intravenous Liposomal Amphotericin B (AmBisome) against Coccidioidal Meningitis in Rabbits

2002 ◽  
Vol 46 (8) ◽  
pp. 2420-2426 ◽  
Author(s):  
Karl V. Clemons ◽  
Raymond A. Sobel ◽  
Paul L. Williams ◽  
Demosthenes Pappagianis ◽  
David A. Stevens
Keyword(s):  
Spinal Cord ◽  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
White Blood Cells ◽  
Clinical Signs ◽  
Liposomal Amphotericin B ◽  
Coccidioides Immitis ◽  
Lower Protein ◽  
Motor Abnormalities ◽  
The Brain

ABSTRACT The efficacy of intravenously administered liposomal amphotericin B (AmBisome [AmBi]) for the treatment of experimental coccidioidal meningitis was compared with those of oral fluconazole (FLC) and intravenously administered conventional amphotericin B (AMB). Male New Zealand White rabbits were infected by intracisternal inoculation of arthroconidia of Coccidioides immitis. Starting 5 days postinfection, animals received one of the following: 5% dextrose water diluent; AMB given at 1 mg/kg of body weight; AmBi given at 7.5, 15, or 22.5 mg/kg intravenously three times per week for 3 weeks; or oral FLC given at 80 mg/kg for 19 days. One week after the cessation of therapy, all survivors were euthanatized, the numbers of CFU remaining in the spinal cord and brain were determined, and histological analyses were performed. All AmBi-, FLC-, or AMB-treated animals survived and had prolonged lengths of survival compared with those for the controls (P < 0.0001). Treated groups had significantly lower numbers of white blood cells and significantly lower protein concentrations in the cerebrospinal fluid compared with those for the controls (P < 0.01 to 0.0005) and had fewer clinical signs of infection (e.g., weight loss, elevated temperature, and neurological abnormalities including motor abnormalities). The mean histological scores for AmBi-treated rabbits were lower than those for FLC-treated and control rabbits (P < 0.016 and 0.0005, respectively); the scores for AMB-treated animals were lower than those for the controls (P < 0.0005) but were similar to those for FLC-treated rabbits. All regimens reduced the numbers of CFU in the brain and spinal cord compared with those for the controls (P ≤0.0005). AmBi-treated animals had 3- to 11-fold lower numbers of CFU than FLC-treated rabbits and 6- to 35-fold lower numbers of CFU than AmB-treated rabbits. Three of eight animals given 15 mg of AmBi per kg had no detectable infection in either tissue, whereas other doses of AmBi or FLC cleared either the brain or the spinal cord of infection in fewer rabbits. In addition, clearance of the infection from both tissues was achieved in none of the rabbits, and neither tissue was cleared of infection in AMB-treated animals. Overall, these data indicate that intravenously administered AmBi is superior to oral FLC or intravenous AMB and that FLC is better than AMB against experimental coccidioidal meningitis. These data indicate that AmBi may offer an improvement in the treatment of coccidioidal meningitis. Additional studies are warranted.

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