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
F dell'Accio
Queen Mary University of London
f.dellaccio@qmul.ac.uk
Meet the Team
Queen Mary, University of London
Queen Mary University London
Queen Mary, University of London
Queen Mary, University of London
Queen Mary, University of London
Utrecht University
University Medical Center Utrecht
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.
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.
Publications
- Caxaria S, Kouvatsos N, Eldridge SE, Alvarez-Fallas M, Thorup AS, Cici D, Barawi A, Arshed A, Strachan D, Carletti G, Huang X, Bharde S, Deniz M, Wilson J, Thomas BL, Pitzalis C, Cantatore FP, Sayilekshmy M, Sikandar S, Luyten FP, Pap T, Sherwood JC, Day AJ, Dell'Accio F. Disease modification and symptom relief in osteoarthritis using a mutated GCP-2/CXCL6 chemokine. EMBO Mol Med. 2023 Jan 11;15(1):e16218. doi: 10.15252/emmm.202216218. Epub 2022 Dec 12. PMID: 36507558; PMCID: PMC9832835
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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.