Inside inflammation: newly discovered receptors are key players in painful conditions

A new mechanism for the excitation of sensory nerves, which play a role in inflammation, has been discovered by researchers at the University of Calgary, in collaboration with colleagues in the US, Italy and the UK (Nat Med 2000;6[2]:134-5). The discovery could lead to new treatments for inflammatory conditions.

The researchers discovered that proteases released from sensory cells involved in the inflammatory process activate a newly discovered class of receptors, proteinase activated receptors 2 (PAR2), that are located on sensory neurons. The findings suggest that substances that can block the PAR2 receptors may eventually become new anti-inflammatory drugs. "This direction has yet to be explored; we will now try to study the role of these receptors in the process of inflammation and pain in models of conditions like colitis," says Morley Hollenberg, professor of pharmacology and therapeutics at the University of Calgary. "The novel thing about our work is the involvement of the nervous system."

An editorial in the British Medical Journal (BMJ 2000;320:331) describes how the US researchers explored the role of tryptase in the inflammatory process. They looked at the interaction of tryptase with PAR2 receptors when mast cells in the vicinity of sensory nerve endings degranulate. "we wanted to establish whether the mast cells were talking to neurons via tryptase," commented Nigel Bunnett of the University of California. The experiments confirmed "that PAR2 receptors on sensory nerves are critical to the inflammatory process."

Ultimately, new anti-inflammatory drugs based on these findings could benefit patients with conditions such as arthritis, inflammatory bowel disease and migraine headaches, but Hollenberg says human trials are a long way off. At this stage, he said, "the work has raised the visibility of this receptor as a target for companies to develop drugs. Companies have been interested in developing drugs to target the PAR1 system, but as yet they have not targeted the PAR2 system."

For Hollenberg, who has worked on the project since 1991, a key aspect of the discovery has been "the coming together of people with unique expertise," none of whom could have completed the research alone.