Newsletter Autumn Winter 2023 Final (24) - Flipbook - Page 6
Mechanisms of inflammatory joint pain: The role of TRPM3 in knee
nociceptors and its interaction with fibroblast-like synoviocytes.
Dr. Javier Aguilera-Lizarraga, University of Cambridge.
Rheumatoid arthritis is a debilitating inflammatory condition affecting over
400,000 people in the UK. In rheumatoid arthritis, joint damage and swelling
occur that produce chronic pain, which in turn decrease an individual9s quality of life.
Rheumatoid arthritis is a complex condition, but it is becoming increasingly clear that
fibroblast-like synoviocytes, a type of cell that lines synovial joints, such as the knee, play an
important role in disease progression .Recent research in our laboratory showed that
molecules produced by these cells during inflammation can increase the sensitivity of sensory
neurons that transmit pain signals. This process results in stronger and/or longer-lasting
neuronal signals and can lead to the development of chronic pain. Therefore, the interaction
between fibroblast-like synoviocytes and sensory neurons might be a crucial factor in the
development of inflammatory joint pain.
We previously showed that TRPV1, an important receptor for the transmission of pain signals in
sensory neurons, plays a key role in inflammatory joint pain and that its function is modulated
by fibroblast-like synoviocytes. However, clinical trials have shown that drugs targeting this
receptor may cause undesired adverse effects. In this study, we aim to establish new
mechanisms in inflammatory joint pain. Thus, we will investigate the role of TRPM3, another
receptor involved in transmitting pain signals. To this end, we will use pharmacological tools to
assess if the TRPM3 receptor is involved in inflammatory joint pain using a model of knee joint
inflammation. Ultimately, this project will provide new insights into the mechanisms underlying
inflammatory joint pain.
REliability of HRDD as a biomarker in Painful diabetic
nEuropathy – a vaLidation study (REPEL)
Dr Anne Marshall, University Liverpool
Damage to the nerves caused by diabetes, diabetic neuropathy, is the
most common complication of diabetes, affecting up to half of all
patients . It primarily affects the feet and can cause severe pain and distressing sensations
which are difficult to treat. Gaps in our understanding of the mechanisms involved in the
development of pain in diabetic neuropathy have led to inadequate treatment.
Damage to the ends of the nerve fibres in diabetes is thought to lead to an increase of pain
signals to the spinal cord. Normally the nerve circuits in the spinal cord would attempt to
suppress these pain signals. However, in animal studies of diabetes, it has been shown that
changes within the spinal cord inappropriately amplify these pain signals rather than
suppressing them – a process called spinal disinhibition.
A biomarker of spinal disinhibition is H-reflex rate dependent depression (HRDD), which can be
tested non-invasively in humans. We have demonstrated that HRDD is impaired in people with
painful diabetic neuropathy and believe that HRDD could be used to identify patients who may
benefit from targeted therapies that reverse spinal disinhibition. However, before we can test this
in large numbers of patients in clinical trials, we need to know whether HRDD readings are reliable
when tested on multiple occasions (repeatability) and when tested by different individuals
(reproducibility). In this prospective study we will determine the reliability of HRDD in the target
clinical population by testing whether the measurements are repeatable and reproducible.
6