Chapter category: Immunology
Cytokines and Peripheral Analgesia
Immune Mechanisms of Pain and Analgesia
Edited by: Halina Machelska and Christoph SteinISBN: 0-306-47692-4
» Get more information about this book at landesbioscience.com «
Chapter authors:
Michael Schafer
[+] view image
Acute transient pain serves as a physiological warning to guard the integrity of the organism. An immediate reflex, e.g., withdrawal of a body part from a heat source, prevents tissue damage. If tissue damage occurs, an inflammatory response develops that triggers mechanisms in both the nervous and the immune systems.1 This results in an ongoing painful state. The inflammatory response consists of a release of cell products such as protones, radicals and adenosine triphosphate, the generation of prostaglandins and bradykinin, and the secretion of cytokines such as interleukin (IL)-1,IL-6, tumor necrosis factor (TNF)-a from inflammatory cells. These inflammatory mediators evoke activation of specific ion channels through the excitation of peripheral nociceptive neurons.1 In addition, they reduce the threshold of peripheral nociceptive neurons through activation of intracellular kinases, resulting in peripheral sensitization.1 This interaction between the immune and nervous systems leads to an increased sensitivity to painful stimuli, i.e., hyperalgesia, and serves the protection of the injured body part to prevent further tissue damage. While this is advantageous in the early period of inflammation, it may have deleterious consequences in an advanced period of inflammation. Consistently, cytokine plasma and tissue concentrations commonly increase to a peak within the first 6 hours and return to baseline values at about 12 hours.2 Pain as a result of neuroimmune interactions is a topic of the chapters by Watkins, and Cunha and Ferreira in this volume.
Concurrently, however, counteractive endogenous mechanisms are being established to inhibit inflammatory pain at the site of tissue injury. These mechanisms are also based on interactions between the immune and nervous systems. Primary sensory neurons express mRNA specific for m-, d- and k-opioid receptors indicating their synthesis in dorsal root ganglia.3,4 After synthesis the receptor proteins are transported from the dorsal root ganglia along the axon to the peripheral nerve terminals.5,6 This axonal transport is directed towards the sensory nerve endings within painful inflamed tissue and is enhanced under inflammatory conditions.5,6 In parallel, the local inflammatory process triggers an enhanced expression of endogenous ligands of these receptors, the opioid peptides, within inflammatory cells.6 These contain mainly b-endorphin but also metenkephalin and dynorphin.7 The opioid peptidecontaining immune cells migrate in a sitedirected manner from the circulation to the painful inflamed tissue (see refs. 8, 9 and the chapters by Mousa, and Machelska in this volume). This migration is increased under inflammatory conditions. The extravasation of leukocytes to the sites of inflammation is comprised of distinct adhesive events. Blockade of these adhesive mechanisms results in a reduced migration of opioidcontaining immune cells (see ref. 9 and the chapter by Machelska in this volume). Importantly, these potentially antinociceptive (analgesic) opioid peptides can be secreted into the surrounding tissue by specific releasing factors. This results in an activation of opioid receptors on sensory nerve endings and can elicit an inhibition of the generation and transmission of painful stimuli. The best described releasing factors so far are corticotropinreleasing factor (CRF-) andIL-1. This book chapter outlines in more detail the role of opioid peptidereleasing factors in endogenous pain control.
Additional chapters from this book:
Anti-Inflammatory Effects of Opioids
Judith S. Walker
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder with its primary manifestations in the joints. The etiology of RA remains obscure, no cure is yet available and sustained ...
Invertebrate Opiate Immune and Neural Signaling
George B. Stefano, Patrick Cadet, Christos M. Rialas, Kirk Mantione, Federico Casares, Yannick Goumon and Wei Zhu
It is increasingly becoming evident that specific chemical signal molecules within a cell and between cells can be the same regardless of whether an organism is an invertebrate or vertebrat...
The ImmuneSuppressive Effects of Pain
Gayle G. Page
The immune-suppressive effects of painful experiences have been studied in both humans and animals for many years. Experimental pain has been induced by such means as electric shock and sur...
Experimental Evidence for Immunomodulatory Effects of Opioids
Paola Sacerdote, Elena Limiroli and Leda Gaspani
In recent years the experimental and clinical research has made it clear that the immune system does not stand alone, but it is profoundly affected by other organ systems, especially the ce...
Opioid Receptor Expression and Intracellular Signaling by Cells Involved in Host Defense and Immunity
Burt M. Sharp
More than two decades ago, Joseph Wybran reported his original insights on the expression of different opioid receptor types by T-cell s. This was based on the differential effects that morphi...
Functional Evidence of Pain Control by the Immune System
Halina Machelska
Pain can be effectively controlled by various endogenous mechanisms. Recent research has shown that these mechanisms are not restricted to the central nervous system. Intrinsic pain inhibition...
Morphological Correlates of Immune-Mediated Peripheral Opioid Analgesia
Shaaban A. Mousa
Secent research has shown that effective inhibition of pain by endogenous mechanisms can be generated within peripheral tissue, outside the central nervous system. Studies using sensitive and ...
Opioid Receptors on Peripheral Sensory Neurons
Christoph Stein
The interaction of immune cellderived opioid peptides with opioid receptors on peripheral terminals of primary afferent (sensory) neurons is one of the most extensively investigated immune mec...
Opioid Peptides in Immune Cells
Eric M. Smith
The roles of opiates and opioids (endogenous peptides with opiate activity) in the immune system have only recently begun to receive rigorous study. The purpose of this chapter is to cover a p...
Cytokines and Peripheral Analgesia
Michael Schafer
Acute transient pain serves as a physiological warning to guard the integrity of the organism. An immediate reflex, e.g., withdrawal of a body part from a heat source, prevents tissue damag...
Peripheral Hyperalgesic Cytokines
Fernando Q. Cunha and Sérgio H. Ferreira
Primary sensory neurons (PSN) become sensitized during inflammation (hyperalgesia) and as a consequence the nociceptors are able to transduce innocuous stimuli into what is perce...
Glial Proinflammatory Cytokines Mediate Exaggerated Pain States: Implications for Clinical Pain
Linda R. Watkins, Erin D. Milligan and Steven F. Maier
When you hurt yourself, you become consciously aware of the pain because a chain of neurons carries the pain message from the injury to the spinal cord, and then from the spinal cor...
