Pain and Neurogenic Inflammation

Pain and inflammation are inextricably linked phenomena. The observation that chemical mediators with combined pro-inflammatory, algesic and/or hyperalgesic activity occur at the site of inflammation is fundamental not only to our present understanding of the inflammatory process but also to our attempts to devise clini cally useful anti-inflammatory therapies. Over a hundred years ago it was recognised that primary sensory neurones play a crucially important "dual" role in inflammation. By affecting the transfer of infor mation from peripheral nociceptors to the spinal cord, a subpopulation of sensory nerves {"pain fibres"} initiate algesia and hyperalgesia, whose sensations are then modified and fine-tuned in the central nervous system. Equally important is the release from the peripheral terminals of sensory neurones of neuropeptides, the acute effects of which are observed as changes in microvascular tone and perme ability leading to neurogenic inflammation. Over the last decade it has become increasingly clear that this view of the func tion of sensory nerves is somewhat over-simplified. For example, the mechanisms underlying hyperalgesia may, in certain circumstances, be mimicked in other condi tions such as the hypersensivity associated with asthma. Furthermore, it has become increasingly evident that over a longer time period the release of neuropeptides from peripheral sensory nerve endings may also have modulating effects on inmune cells and that this may be relevant to chronic inflammatory disease and possibly also to inflammatory hyperalgesia.

A comparative discussion of A? and C fibres in different tissues.- The roles of spinal receptors in nociceptive responses.- Cutaneous hyperalgesia.- Capsaicin and pain mechanisms.- Nitric oxide and inflammatory pain.- Interactions between kinins and the inflammatory pain process.- Sensory neuropeptides, neurogenic inflammation and inflammatory cells.- Inflammatory pain and the joint.- Nerve growth factor and sensory nerve function.- The relationship between hyperalgesia and hyperresponsiveness in the lung.- Neuropeptides and the respiratory tract: Relevance to asthma and rhinitis.- Neuropeptides and the gut: Tachykinins and calcitonin gene-related peptide in intestinal inflammation and pain.- Regulation of meningeal blood flow by neuropeptides: Relevance to migraine.- Sensory peptides: Effects in ageing and wound healing.- Calcitonin gene-related peptides and their receptors.- Tachykinin receptors and the potential of tachykinin antagonists as clinically effective analgesics and anti-inflammatory agents.