Mediators share common ground: Pain and Neurogenic Inflammation [Series: Progress in Inflammation Research (edited by Michael J. Parnham)], edited by Susan D. Brain and Phillip K. Moore

Abstract

Birkhauser Verlag, 1999. 258 DM (hardback) (300 pages)ISBN 3 7643 5875 0Our own experience tells us that inflammation and pain are related, and several experimental studies have shown us that each phenomenon is capable of eliciting the other. Pro-inflammatory substances that are released from various cells at the site of injury act on peripheral sensory neurones to produce pain and hyperalgesia, a state of increased responsiveness to painful stimuli. Activation of certain primary afferent neurones causes the release of pro-inflammatory peptides such as substance P and calcitonin gene-related peptide (CGRP); these peptides subsequently produce changes in microvasular tone and permeability, which results in plasma extravasation and oedema in a phenomenon known as neurogenic inflammation. In addition, release of neuropeptides from peripheral sensory nerve endings might modulate immune cells – a mechanism that might be relevant to chronic inflammatory diseases.Although many reviews and books already describe the mechanisms of pain and inflammation, most of these publications focus on either mechanisms of pain transmission or the inflammatory process, but not both together. This book aims to provide an integrated treatment in which pain and inflammation are critically evaluated and compared.Of fundamental importance for understanding pain and neurogenic inflammation are the characteristics of different classes of primary afferent neurones. The neurones that appear to be particularly important in pain transmission and neurogenic inflammation are the slowly conducting, small-diameter, unmyelinated, peptide-containing C-fibres. Capsaicin, the pungent ingredient present in hot peppers, produces pain and neurogenic inflammation by activating C-fibres. Because of this characteristic, capsaicin has been a valuable tool for increasing our knowledge about sensory neurone biology. Capsaicin has also been used in clinical pain studies of cutaneous hyperalgesia. Most studies of the involvement of sensory neurones in pain and neurogenic inflammation have focused on cutaneous somatosensory afferents. However, sensory fibres innervating different tissues might show fundamental differences, so care must be taken in extrapolating findings from cutaneous sensory fibres to peripheral neurones of joints and airways.Tissue injury and inflammation result in the peripheral release of a multitude of inflammatory factors that include kinins, nitric oxide, nerve growth factor and neuropeptides such as substance P and CGRP. The already complex interaction between these factors in the periphery is further complicated by the fact that most or possibly all of these substances are also present in the spinal cord. In addition to the effects of these inflammatory factors in the periphery, they contribute to neuronal sensitization and the behavioural phenomenon of hyperalgesia at the level of the spinal cord.An extensive literature describes the role of the pro-inflammatory and hyperalgesic peptides substance P and CGRP in various physiological functions and disease states, including gastrointestinal function, migraine, wound healing, asthma and rhinitis. Substance P and CGRP mediate their effects by interacting with specific membrane receptors, the tachykinin (NK1–3) and CGRP1–2 receptors. Although the tachykinin receptors have been cloned, the suggestion of multiple CGRP receptors is based on pharmacological evidence. Substance P is the preferred agonist for the NK1 receptor. In the belief that activation of NK1 receptors by substance P is involved in pain transmission, non-peptide receptor antagonists for the NK1 receptor have been developed for potential use as analgesics. However, experimental results have been inconsistent and more recent clinical studies have been disappointing, which suggests that NK1 receptor blockade might not be a useful analgesic strategy.Each chapter contains an interesting and comprehensive review of its specific topic. However, although the self-declared purpose of the book is to integrate discussion of pain and inflammation, most of its chapters focus on one topic or the other. The structure of the book is somewhat confusing and its 16 chapters are not organized into sections. The book is excellent for a newcomer to the area of pain and neurogenic inflammation who would like to read review papers on the two subjects. However, for the more experienced pain or inflammation scientist the book offers little new information.