Control of alternative pre-mRNA splicing in the generation of inflammation and pain

Lead Research Organisation: University of Nottingham
Department Name: School of Life Sciences


The control of alternative pre-mRNA splicing in the generation of inflammation and pain.
Supervisors: Lucy Donaldson and David Walsh.
Pain is a fundamental sensation that serves to alert the body to potential or actual damage, and to invoke protective responses to prevent further damage. Damage to tissues stimulates a complex series of events, in multiple cell types, that are part of the repair process. In some circumstances cellular changes do not result in repair, but instead lead to continued damage and, pain. Inflammation contributes to pain and tissue damage in arthritis across mammalian species, so controlling inflammation can have benefit for both animal and human welfare.
Expression of different proteins by alternative RNA splicing is increasingly recognised as a key pathogenetic mechanism, although its contribution and control in inflammation and pain remains to be explored. We have evidence that in fibroblast-like synoviocytes, the cells that line the joint space, fundamental inflammatory responses such as immune cell adherence are controlled by alternative pre-mRNA splicing, particularly of the growth factor family vascular endothelial growth factor (VEGF).
This project will combine studies in animals and human tissue to interrogate the control of alternative pre-mRNA splicing in pain generation. The focus will be on the alternative splicing controls of VEGF but other targets might also be explored. You will test the hypothesis that changes in alternative splicing actively contribute to inflammation and pain by: 1. localising key components of the alternative splicing machinery in inflamed/damaged human synovial tissue to determine cell types in which this mechanism is active; 2. using isolated synoviocytes to model arthritic inflammation in vitro, to determine mechanisms through which alternative splicing is regulated under these conditions, and test novel drugs that could alter these processes, and 3. Using experimental animals to test effects of alternative splicing on arthritis pain mechanisms.
The project will be fully supported by the expertise and biorepositories within the Arthritis Research UK Pain Centre at the University of Nottingham (


10 25 50

publication icon
Durrant A (2018) A role for pericytes in chronic pain? in Current Opinion in Supportive & Palliative Care

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M008770/1 30/09/2015 31/03/2024
1804143 Studentship BB/M008770/1 30/09/2016 29/09/2020
Description We have demonstrated that a novel class of drugs have the ability to reverse chemotherapy induced sensitisation of sensory neurons in vitro. We have also demonstrated that these novel drugs are provide a degree of neuroprotection to neurons treated with chemotherapy.
Exploitation Route Further confirmation of novel drug potential via in vivo experiments and if successful, eventual application in various clinical trials to prove drug efficacy.
Sectors Healthcare

Pharmaceuticals and Medical Biotechnology

Description Visit to Former Undergraduate Course 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact Attended a careers day for my undergraduate degree to talk about how to get access to a PhD programme and what day to day life entails as a PhD student. Answered student questions and delivered a short presentation to ~40 undergrad students. Received feedback that a couple of students would seek to pursue a PhD in the future.
Year(s) Of Engagement Activity 2016,2019,2020