Targeting nociplastic pain in arthritis

Concept

Pain is the main disabling symptom in arthritis. Inflammation and tissue damage cause nociceptive pain, which normally improves with injury healing and disease control. Many patients develop nociplastic pain, which persists in the absence of inflammation and tissue damage. It was discovered that, in mice, ablating Nav1.8-expressing nociceptors preserves nociceptive pain but prevents the establishment of nociplastic pain. By comparing the transcriptome of patients with prevalently nociceptive versus prevalently nociplastic pain from highly characterized prospective cohorts and cross-referencing with transcriptomics data in animal models of rheumatoid arthritis, osteoarthritis and nociplastic pain, the group will identify transcripts associated with the development of nociplastic pain. After an in-silico analysis to predict and prioritize key molecular players amenable for targeting, the group will use gain- and loss-of-function experiments in animal models to determine which of these genes/pathways are essential for the transition from nociceptive to nociplastic pain.

Facts and Figures

Project Lead
F dell'Accio
Queen Mary University of London
f.dellaccio@qmul.ac.uk
FOREUM research grant: € 599.908
2021–2024

Meet the Team

F dell'Accio
Queen Mary University of London
S Sikandar
Queen Mary, University of London
AS Thorup
Queen Mary University London
S Eldridge
Queen Mary, University of London
C Pitzalis
Queen Mary, University of London
M Lewis
Queen Mary, University of London
N Eijkelkamp
Utrecht University
A Pandit
University Medical Center Utrecht
A Moqrich
Institute of Marseille

Objectives

Objective 1. Identification of signatures of nociplastic vs nociceptive pain using transcriptomics data from patient cohorts and animal models.

Objective 2. Prioritization strategy for candidate gene targets.

Objective 3. Validation of drug targets in animal models of pain, osteoarthritis and inflammatory arthritis.

Patient Voice

A large proportion of patients with arthritis and all patients with fibromyalgia are disabled by nociplastic pain, resulting in absenteeism, huge costs and loss of work capacity worth billions. Treating nociplastic pain would restore the work capacity of these patients, their quality of life and independence.

Goals/Milestones

1-12 months: completion and analysis of transcriptomics data

18 months: prioritization of targets

24 months: completed in vitro validation of at least 5 targets.