Investigating how the nerve proteins HCN2 and AT2 contribute to pain in arthritis

Disease - Rheumatoid arthritis, osteoarthritis, knee pain

Lead applicant - Professor Peter McNaughton

Organisation - King's College London

Type of grant - Research Award

Status of grant - Active

Amount of the original award - £232,985.14

Start date - 1 June 2017

Reference - 21522

Public Summary

What are the aims of this research?

Pain and swelling are common symptoms for people with arthritis, but current treatments don’t work well for all of those affected, and can come with side effects. The overall aim of this project is to identify new mechanisms underlying the pain of arthritis, in order to identify new targets for the development of future pain relief drugs. The researchers will specifically look at the role of two proteins, called HCN2 and AT2, in the inflammation and pain experienced in arthritis.

Why is this research important?

There are two different types of pain that people with arthritis may experience: inflammatory and neuropathic. The first, inflammatory pain, is caused by joint tissue damage which activates pain nerves. HCN2 is a protein found on nerves that is known to play a crucial role in this process. The second, neuropathic pain, is caused by direct damage to the nervous system, and a different nerve protein called AT2 is important in this pain process. Recent studies show that these proteins may work together in rheumatoid arthritis and osteoarthritis to cause both types of pain.

The researchers will use mice with arthritis to see whether HCN2 underlies arthritic pain by blocking its action, as well as seeing if, and how, AT2 works with HCN2 to cause pain. This research is important as the development of drugs that could be used to block these two targets may be useful for pain relief in arthritis.

How will the findings benefit patients?

Identification of the role these two proteins have in arthritis pain, and whether blocking their action leads to effective pain relief in arthritis, will allow for the development of new drugs. New drugs following on from this research that achieve effective pain relief without the major side effects of current treatments will provide a significant improvement in patient mobility and freedom from pain.