Investigating pain and whether it underlies altered behaviour in osteoarthritis zebrafish mutants

Abstract

Osteoarthritis (OA) is a chronic, degenerative disease affecting the entire joint, where patients report chronic pain, reduced mobility and range of motion. Cases rise each year in line with the ageing population and OA represents the most frequent cause of disability. There is currently no cure and at present treatment and disease management are often focused on pain relief and joint replacement. Reported joint pain does not always correlate with pathological severity, highlighting a complex relationship between pain and joint phenotype. Recent work has shown that genetically encoded pre-symptomatic joint shape changes can predispose individuals to OA, but the relationship between pain and joint morphology remain relatively poorly understood. Here I use zebrafish as an animal model to study the relationship between joint morphology, behaviour and pain. I show that 5dpf homozygous col11a2ˢᵃ¹⁸³²⁴ and homozygous barx1ˢᵃ¹⁰³⁶⁰ larval zebrafish carrying mutations in genes associated with OA show altered joint phenotypes and abnormal changes to jaw joint movement and to swim behaviour. I found that there are differences in the average spinal curvature of 1 year homozygous col11a2ˢᵃ¹⁸³²⁴ mutants in comparison to age matched wild types, which correlate with premature degeneration of the vertebral column. This is also observed between 1 year and 3 year old wild type fish. Abnormal movement in larval or adult stages could not be rescued by lidocaine-based analgesia concluding that underlying joint morphology appears to be the causative factor and not sources of peripheral pain. Further work is required to investigate the role of central mechanisms of pain in these mutants. The results suggest that administration of analgesics to fish with severe radiographic OA is unlikely to have any effect to restore normal movement.

Date of Award	22 Mar 2022
Original language	English
Awarding Institution	University of Bristol
Supervisor	Chrissy L Hammond (Supervisor) & Beck J Richardson (Supervisor)