Pain is a fundamental biological signal essential for survival, yet it also represents one of the most pervasive medical challenges worldwide. Clinically, pain manifests in diverse forms, including inflammatory pain, cancer-related pain, migraine, and neuropathic pain arising from injury or dysfunction of the nervous system. Among these, neuropathic and chronic pain conditions are particularly resistant to conventional analgesics such as nonsteroidal anti-inflammatory drugs and opioids. Moreover, the abuse of opioid analgesics has contributed to severe public health consequences, underscoring the urgent need for alternative, non-addictive therapeutic strategies.
In our preliminary studies, we employed AAV-mediated gene knockout approaches to functionally interrogate a series of candidate genes in mouse models. We found that deletion of specific genes led to a significant reduction in behavioral responses to noxious stimuli like pinch and poke, indicating a potential role for these genes in modulating pain sensitivity. These findings raise the possibility that variation in the expression or function of the same genes may also contribute to altered pain perception in humans.
To test this hypothesis and explore its translational potential at the population level, access to large-scale human genotype and phenotype data is essential. The UK Biobank provides a unique resource that integrates genetic variation with detailed pain-related phenotypes, enabling downstream analyses such as genome-wide association studies (GWAS) to explore the pleiotropic effects of these genes.
By leveraging these data, we aim to examine whether loss-of-function variants or altered expression of the identified candidate genes are associated with pain-related traits in humans. Such analyses may help establish translational relevance between animal models and human pain biology, and ultimately inform the identification of novel molecular targets for analgesic drug development.
