Chronic pain is a complex and heterogeneous condition that often arises from the interaction of genetic, environmental and physiological factors. Despite advances in treatment, current therapies are often ineffective, reflecting our incomplete understanding of the molecular mechanisms that make some individuals more vulnerable to persistent pain. One critical but insufficiently explored dimension is the role of genetic variability in ion channels and other molecular pathways that regulate nociception and pain sensitisation. Ion channels, particularly those expressed in sensory neurons, act as molecular sensors of noxious stimuli, playing a central role in neuronal excitability, signal transduction and the development of pain hypersensitivity.
This project will leverage the extensive genetic and phenotypic resources of the UK Biobank to identify genetic variants that influence susceptibility to chronic pain. Specifically, we will: i) characterise pain phenotypes using questionnaire data, clinical records and quality of life measures; ii) perform large-scale genetic analyses to detect associations between chronic pain and variants in ion channel genes, as well as in other loci implicated in pain perception and neuronal signalling; iii) integrate these genetic findings with medical history to uncover molecular and physiological determinants of pain chronification. We expect to identify genetic polymorphisms that modulate individual predisposition to pain and establish their functional relevance in nociceptive pathways.
