KININS AND THEIR RECEPTORS IN HYPERALGESIA

Kinins (bradykinin, kallidin) are produced at sites of injury and infl ammation and serve a critical role in signaling tissue distress as wel l as organising tissue responsiveness to injury. The acute activation and prolonged sensitization of fine afferents, to produce pain and hyp eralgesia, are important in the protective responses that occur to min imize further tissue injury. These effects occur via activation of B-2 receptors present on sensory neurons, resulting in a change of membra ne excitability and altered cellular neurochemistry. B-2 receptor acti vation of a variety of tissues including postganglionic sympathetic fi bres stimulates the production of several proinflammatory mediators, i ncluding prostanoids and cytokines, which interact with kinins and con tribute to inflammation and hyperalgesia. Increased expression of B-1 receptors plays a prominent role in inflammatory hyperalgesia, but fur ther characterization of the cellular mechanism is required. A role fo r kinins and kinin receptors in central pathophysiologies (trauma, isc hemia, infection) needs examination. The evidence for modulation of no ciception and central pain generation is compelling, as central bradyk inin administration causes hyperalgesia, whereas B-2 antagonists are a ntinociceptive. The basis for these effects should be urgently investi gated. Such data will add further support to the utilization of bradyk inin receptor antagonists for the treatment of peripheral and central pain.