The role of the nerve growth mediator semaphorin 3A in joint pain

Disease - Osteoarthritis, knee pain

Lead applicant - Professor Chantal Chenu

Organisation - The Royal Veterinary College

Type of grant - Research Award

Status of grant - Active

Amount of the original award - £215,016.1

Start date - 4 December 2017

Reference - 21526

Public Summary

What are the aims of this research?

Semaphorins are molecules in the joint that provide guidance for nerve growth. One type of semaphorin, called semaphorin-3A, is produced by the cells that make cartilage and is important in stopping the growth of nerves. It has been found to be reduced as we age and its presence is also significantly decreased in people with osteoarthritis. This project aims to see whether a reduction in semaphorin-3A in the joint leads to uncontrolled local nerve ingrowth and joint pain, and whether replacing the lost semaphorin-3A can reverse this and relieve pain symptoms.

Why is this research important?

Osteoarthritis is the most common form of joint disease and is a major cause of pain in and around affected joints. Current pain relief drugs, such as paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs), are often inadequate to relieve pain in people with osteoarthritis, and so there is a real need for more effective treatment options.

Nerves present in the joint can change in structure, location and number. For example, they can sprout into areas where nerves are only present in low numbers or are not normally found at all, such as the cartilage. It is thought that in musculoskeletal conditions these nerve changes can cause the pain often associated with them, however, the reason and method of this nerve sprouting is unknown.

The researchers will use mice with osteoarthritis to see whether levels of semaphorin-3A are linked to nerve sprouting, pain levels and severity of joint damage, and whether administration of this molecule can reduce pain levels.

How will the findings benefit patients?

Findings from this research can be used to help give a wider understanding into the pain mechanisms of osteoarthritis, particularly as this project will focus on how nerve growth relates to pain sensation. Importantly, it will see if, and how, semaphorin-3A can be used to relieve pain symptoms, creating a new target for pain relief. Development of new drug targets will have a major impact on the quality of life of those experiencing chronic pain due to osteoarthritis.