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CNS immune interface

Reporter: Komal Ingle, BSc, MSc

Neuroimmunology is a field that investigates the bi-directional communication between the nervous system (CNS and PNS) and the immune system. While these two physiological systems were traditionally thought to act independently and that the brain was a privileged site protected by the blood–brain barrier (BBB), researchers now appreciate the highly organized cross talk between the immune and nervous systems in health and disease. The CNS communicates with the immune system via hormonal and neural pathways. The hormonal pathway is predominantly via the HPA axis, which is the primary stress center in rodents, primates, and humans. The neural pathway is mediated via the sympathetic and parasympathetic (the vagus nerve) response. In turn, the immune system signals the CNS via cytokines released by activated immune cells in the periphery but also through activated microglia and astrocytes in the spinal cord and brain. The peripheral inflammation can lead to central proinflammatory milieu and ultimately to sickness behaviour defined as a set of behavioural changes that develop in individuals during the course of systemic inflammation (i.e., fever, lethargy, hyperalgesia). The peripheral inflammation can lead to central proinflammatory milieu and ultimately to sickness behaviour defined as a set of behavioural changes that develop in individuals during the course of systemic inflammation (i.e., fever, lethargy, hyperalgesia), Signals, originating from cellular and molecular elements of the immune system itself, constitute a level of autoregulation. There is also evidence of another more integrative level of regulation mediated by neuroendocrine signals

Pathological pain and the neuroimmune interface    

The idea that pain and immunity might be associated beyond an acute response first arose from clinical observations in the 1970s that patients with chronic pain exhibited other symptoms, in addition to hyperalgesia, that parallel the classical systemic sickness response — including lethargy, depression and anxiety. The concomitance of sickness behaviors with chronic pain is therefore suggestive of underlying immune activity. Efforts to identify the origin and nature of the immune mediators involved soon followed, leading to the discovery that elevated peripheral levels of interleukin-1β (IL-1β) both induced hyperalgesia per se and mediated sickness-induced hyperalgesia1,2 . Although peripheral sensitization of pain fibers at local tissue sites of inflammation has a key role in heightening pain from those regions, these peripheral observations were soon extended with the discovery of a central nervous system (CNS) mechanism of action for IL-1β and other cytokines

Physiological pain processing  

Pain (either nociceptive pain or inflammatory pain) is protective and adaptive, warning the individual to escape the pain-inducing stimulus and to protect the injured tissue site during healing. The basic scientific understanding of sensory processing and modulation has been dramatically improved by the development of pain assays that recreate some elements of clinical pain syndromes (BOX 1). Painful stimuli (for example, mechanical, thermal and chemical) are initially transduced into neuronal electrical activity and conducted from the peripheral stimulus site to the CNS along a series of well-characterized peripheral nociceptive sensory neurons (first-order primary afferent neurons). The nociceptive signal is then transmitted at central synapses through the release of a variety of neurotransmitters that have the potential to excite second-order nociceptive projection neurons in the spinal dorsal horn or hindbrain (FIG. 1). This process of nociception can occur through several mechanisms involving glutamate and neuropeptides (for example, substance P or calcitonin gene-related peptide (CGRP)). Glutamate activates postsynaptic glutamate AMPA (α-amino-3 -hydroxy-5-methyl-4-isoxazole proprionic acid) and kainate receptors on second-order nociceptive projection neurons. Interestingly, these receptor systems are not all engaged equally in response to different types of pain. Modification of the nociceptive signal can occur at the level of the spinal cord through activation of local GABAergic (that produce γ-aminobutyric acid) and glycinergic inhibitory interneurons.

Reference

• The immune response evokes changes in brain noradrenergic neurons H Besedovsky, A del Rey, E Sorkin, M Da Prada, R Burri, C Honegger PMID: 6867729 DOI: 10.1126/science.6867729
• Pathological pain and the neuroimmune interface  Peter M Grace ¹, Mark R Hutchinson ¹, Steven F Maier ², Linda R Watkins ² Affiliations expand PMID: 24577438 PMCID: PMC5525062  DOI: 10.1038/nri3621
• Molecular and Functional Neuroscience in Immunity Valentin A Pavlov ¹, Sangeeta S Chavan ¹, Kevin J Tracey ¹ Affiliations expand PMID: 29677475 PMCID: PMC6057146 DOI: 10.1146/annurev-immunol-042617-053158

Other related articles published in this Open Access Scientific Journal include the following:

VOLUME 3: The Immune System and Therapeutics

(Series D: BioMedicine & Immunology) Kindle Edition. On Amazon.com since September 4, 2017

Author, Curator and Editor: Larry H Bernstein, MD, FCAP

https://www.amazon.com/dp/B075CXHY1B

Chapter 10: Neuro-Immunology

Introduction

This chapter is mainly concerned with Alzheimer’s Disease, but also a stress response pathway, neurotransmitters and signaling.

10.1 Alzheimer’s Disease: Novel Therapeutical Approaches — Articles of Note @PharmaceuticalIntelligence.com

Curators: Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

Alzheimer’s Disease: Novel Therapeutical Approaches — Articles of Note @PharmaceuticalIntelligence.com

10.2 BWH Researchers: Genetic Variations can Influence Immune Cell Function: Risk Factors for Alzheimer’s Disease, DM, and MS later in life

Reporter: Aviva Lev-Ari, PhD, RN

BWH Researchers: Genetic Variations can Influence Immune Cell Function: Risk Factors for Alzheimer’s Disease,DM, and MS later in life

10.3 Drugs that activate this novel stress response pathway, which they call the mitochondrial-to-cytosolic stress response, protected both nematodes and cultured human cells with Huntington´s disease from protein-folding damage.

Reporter: Aviva Lev-Ari, PhD, RN

Drugs that activate this novel stress response pathway, which they call the mitochondrial-to-cytosolic stress response, protected both nematodes and cultured human cells with Huntington´s disease from protein-folding damage.

10.4 Role of Neurotransmitters and other such Neurosignaling Molecules

Curator: Larry H Bernstein, MD, FCAP

Role of Neurotransmitters and other such Neurosignaling Molecules