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Pathogenesis and Mechanisms of Inflammation and Pain

An Overview

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Abstract

Pain is perceived through activation of the endings of nociceptive afferent nerves by pain-producing substances released from tissue. These nerves in turn activate nociceptive nerve cells in the dorsal horn of the spinal cord through the release of excitatory amino acids and neuropeptides. The activation of the nociceptive afferents can be amplified after repetitive stimulation via the production of nitric oxide, which facilitates the release of excitatory amino acid transmitters.

Pain is one of the cardinal signs of inflammation, the response of tissue to frank or immune damage or infection. The inflammatory response is characterised by vasodilation, oedema and a marked local accumulation of white blood cells. Many intercellular messengers, or cytokines, are responsible for the various stages of inflammation, but tumour necrosis factor seems to be a significant initiator of the response.

The severe pain that accompanies inflammatory disease such as rheumatoid arthritis is caused by the action of pain-producing substances such as kinins on nociceptor neurons sensitised by locally produced prostaglandins, and perhaps sympathomimetics released from sympathetic nerves. The first-line treatment of inflammatory pain is the use of nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit the cyclo-oxygenase enzyme (COX) which produces the hyperalgesic prostaglandins from their substrate arachidonic acid. Since prostaglandins produced in inflammation are formed by an induced COX (COX-2), distinct from that which produces the cytoprotective prostaglandins, NSAIDs that selectively inhibit COX-2 may provide effective therapy without gastrotoxicity Further clinical experience is required to establish the most effective therapy for inflammatory pain.

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Authors and Affiliations

  1. The William Harvey Research Institute, St Bartholomew’s and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, Charterhouse Square, London, EC1M 6BQ, England

    Regina M. Botting

  2. London, England

    Jack H. Botting

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  1. Regina M. Botting
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  2. Jack H. Botting
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Botting, R.M., Botting, J.H. Pathogenesis and Mechanisms of Inflammation and Pain. Clin. Drug Investig. 19 (Suppl 2), 1–7 (2000). https://doi.org/10.2165/00044011-200019002-00001

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