Bradykinin

Bradykinin is a potent inflammatory peptide messenger. It is synthesised by kallikrein from the precursor kallidin and is made up of only nine amino acids.

It is released from damaged tissue following injury or with inflammation. Mast cells also release bradykinin and in the vascular system it acts as a vasodilator, increases vessel permeability, and stimulates the formation of prostacyclin.

In the nociceptive system it is a very potent pain-producing substance. Following the release with injury or inflammation, it excites a high percentage or nociceptors and sensitises them to other noxious stimuli. The sensitisation occurs through activation of B1 and B2 receptors.

Bradykinin Receptors

The B1 and B2 receptors are coupled to G proteins. In doing so they are involved in second messenger signalling at the site of the nerve endings. B2 is expressed constitutively, and B1 with trauma and inflammation.

B2 Receptor

In the normal state with intact tissue, bradykinin binds to the B2 receptor, with B2 being expressed constitutively in both the central and peripheral nervous system.

When bradykinin activates B2, there is direct stimulation of nociceptors (C & Aδ fibres). Kinins cause sensitisation of sensory fibres to thermal, chemical, and mechanical stimuli. There is a synergy between bradykinin and other inflammatory mediators.

There is a cascade of intracellular reactions through the protein kinase C (PKC) pathway that results in an increase in sodium conductance causing membrane depolarisation and influx of calcium through voltage gated calcium channels.

B1 Receptor

With trauma or inflammation, B1 is synthesised by the nociceptor cell body and transported to the nerve ending membrane. B1 production is an important aspect of neural sensitisation.