MICA: Exosomes and microRNAs regulate neuro-immune interactions in chronic pain

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Chronic pain after nerve damage or inflammatory arthritis is a debilitating condition in which the pain experience persists for long time. Pain is a persistent symptom following injury to nerve or in rheumatoid arthritis (RA) whereby pain remains even after suppression of joint disease with medicines. Chronic pain is difficult to treat, with current drugs being relatively ineffective and often having significant side effects. Therefore, a better understanding of the mechanisms responsible for persistence of pain can bring new ideas on how to prevent or attenuate chronic pain and facilitate the development of new medicines. We use mice in our studies as they also demonstrate pain-related behaviour in their hind paws that persists for several weeks in models of joint arthritis and peripheral neuropathy (PN). Pain is a sign of both RA and PN, where blood cells enter the joint and the injured nerve and produce factors that activate pain nerves: these nerves carry pain signals from the joint or injured nerve to the spinal cord on their way to the brain where pain is felt. We discovered that blood-derived cells are not only in the joint or the injured nerve, but they are also around pain cells outside the joint and injured nerve in a structure that is called dorsal root ganglia (DRG). At this DRG site, far away from the swollen joint and injured nerve, blood-derived cell influence pain nerves and favour pain sensation. In these blood-derived cells we have identified new targets that can be exploited to regulate pain activity and may constitute novel approaches to treating persistent pain. These new targets are small strands of genetic material, produced in the pain cells of the DRG and packaged in small microstructures. Pain cells handover these particles to blood-derived cells to regulate their activity by increasing production of chemicals that increase pain sensitivity. We have identified a new way to target this genetic material within blood-derived cells.In this project, we will use a variety of methods to assess the activity of blood-derived cells in animal models of pain, and determine the effects of this activity on the nerve cells that carry pain signals. We will then measure readouts of pain when specific activity in blood-derived cells has been either blocked. This study will allow us to determine the therapeutic potential of targets in blood-derived cells for the treatment of persistent pain: both chronic pain after nerve damage or inflammatory arthritis will be studied.The ultimate aim of our research is to provide new information that will help in the design of novel pain-relieving medicines, thus allowing chronic pain treatments to be more effective to ultimately improve the quality of life of patients.