Kinins and their receptors in hyperalgesia

Abstract

Kinins (bradykinin, kallidin) are produced at sites of injury and inflammation and serve a critical role in signaling tissue distress as well as organising tissue responsiveness to injury. The acute activation and prolonged sensitization of fine afferents, to produce pain and hyperalgesia, are important in the protective responses that occur to minimize further tissue injury. These effects occur via activation of B2 receptors present on sensory neurons, resulting in a change of membrane excitability and altered cellular neurochemistry. B2 receptor activation of a variety of tissues including postganglionic sympathetic fibres stimulates the production of several proinflammatory mediators, including prostanoids and cytokines, which interact with kinins and contribute to inflammation and hyperalgesia. Increased expression of B1 receptors plays a prominent role in inflammatory hyperalgesia, but further characterization of the cellular mechanism is required. A role for kinins and kinin receptors in central pathophysiologies (trauma, ischemia, infection) needs examination. The evidence for modulation of nociception and central pain generation is compelling, as central bradykinin administration causes hyperalgesia, whereas B2 antagonists are antinociceptive. The basis for these effects should be urgently investigated. Such data will add further support to the utilization of bradykinin receptor antagonists for the treatment of peripheral and central pain.

Fever-like temperature modification differentially affects in vitro signaling of bradykinin B1 and B2 receptors

“…Specifically, B 1 R downstream signal transduction is significantly enhanced under hyperthermic conditions (418C), supporting the notion that B 2 R activation governs the physiological kinin effects, whereas the B 1 R prolongs and amplifies these effects under pathological conditions (Dray, 1997).…”

Hypoalgesia and altered inflammatory responses in mice lacking kinin B1 receptors

“…Kinins exert a critical role in acute pain by acting directly on A␦-and C-fiber sensory neurons or indirectly by releasing inflammatory mediators that sensitize or activate these nociceptors (21). Here we tested whether mice lacking B1 receptors exhibited hypoalgesia in acute behavioral assays.…”

Kallikrein – Kinin System and Coagulation System in Inflammatory Bowel Diseases

“…In addition in chronic inflammation B1R seems to be important in neutrophil accumulation in inflamed tissue (McLean et al, 2000). Both B1R and B2R are involved in onset and maintenance of nociceptive alterations and inflammatory www.intechopen.com pain perceptions (Drey, 1997;Rupniak et al, 1997). Research on involvement of B2Rs in inflammatory states has progressed more quickly than that on B1Rs, and it was favored by the systematic development of selective peptidic B2R antagonists by the pharmaceutical companies, at this time.…”

“…In human study it has been demonstrated a positive staining for TK, kallistatin and the B1R (but not the B2R) in macrophages forming granuloma and for B1R in plasmocytes in the border of granulomas which emphasizes the close relationship between the immune responses important in IBD and the inflammatory mediators including the ITK -kinins. Kinins may also evoke pain by stimulating sensory nerves to mechanical stimuli and other chemical mediators and, in turn, causes hyperalgesia (Drey, 1997). The role of B1R and its agonists in inflammatory pain has been shown in animals (Rupniak et al, 1997).…”