Bradykinin and inflammatory pain

A Dray, M Perkins - Trends in neurosciences, 1993 - cell.com
A Dray, M Perkins
Trends in neurosciences, 1993cell.com
There is compelling evidence linking bradykinin (BK) with the pathophysiological processes
that accompany tissue damage and inflammation, especially the production of pare and
hyperalgesia. Several mechanisms have been proposed to account for hyperalgesia
including the direct activation of nociceptors as well as sensitization of nociceptors through
the production of prostanoids or the release of other mediators. In keeping with this,
antagonists of the BK B2 receptor are efficacious analgesic and anti-inflammatory agents in …
There is compelling evidence linking bradykinin (BK) with the pathophysiological processes that accompany tissue damage and inflammation, especially the production of pare and hyperalgesia. Several mechanisms have been proposed to account for hyperalgesia including the direct activation of nociceptors as well as sensitization of nociceptors through the production of prostanoids or the release of other mediators. In keeping with this, antagonists of the BK B2 receptor are efficacious analgesic and anti-inflammatory agents in acute inflammatory pain. More recently it has been suggested that when inflammation is prolonged, BK B1 receptors, which are not expressed in healthy tissues to a significant degree, also play an important role in the maintenance of hyperalgesia. This may be one of a number of adaptive mechanisms that occur peripherally and centrally following the prolonged activation of nociceptors during inflammation or injury.
The major kinins, including the nonapeptide bradykinin (BK) and kallidin (Lys-BK), are made de novo from high and low molecular weight kininogen precursors'2. This chain of events follows the activation of tissue and plasma kallikreins by pathophysiological stimuli such as tissue trauma, inflammation, anoxia and low pH. Kallidin and BK appear to act on tissues in a similar manner, although BK has been more extensively studied. Newly formed BK acts locally close to its site of production on a wide variety of tissues, both neural and non-neural, with effects ranging from smooth muscle contraction, glandular secretion and immune cell stimulation, to sensitization and activation of sensory and sympathetic neurones (Fig. 1). The effects on neural tissues are of particular significance as BK is increasingly implicated in the aetiology of a number of pain conditions including cardiac pain and pain following tissue anoxia, as well as the pain associated with inflammation and rheumatoid diseases 2-~.
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