King’s College Hospital NHS Foundation Trust

UKRI Gateway to Research · FY 2026 · 2026-08

Neuropathic pain is linked to increased activity in pain relevant subgroups of sensory neurons1–3. One of the key reasons for the lack of effective treatments is the incomplete understanding of the neurobiological mechanisms underlying chronic neuropathic pain, particularly in the context of human-specific pain pathways 4–6. While animal models have provided valuable insights, they do not fully recapitulate human pain experiences due to significant species differences, especially in the structure and function of sensory neurons 4,7,8, which has led to significant translational burdens in the development of new pain therapies4,7,9. Here, we aim to leverage on our diverse, interdisciplinary team focusing on human sensory neurons form organ donors (project 1) and use our internationally acknowledged expertise in state-of-the-art electrophysiological techniques (Patch-Seq, project 2), and advanced genomics (single-cell long-read RNAseq, project 3), combined with neurophysiology measures on probands and patients (microneurography, project 4) to fill these critical knowledge gaps and identify novel therapeutic targets. The project will create a multimodal atlas of human data, which will impel research around the world to help millions of patients suffering from neuropathic pain. Access to human material and especially the combination with state of the art research technologies is rare 5,6. By utilizing human tissue obtained from organ donors, this project will overcome the severe limitations of rodent models, ensuring that findings are directly applicable to human pain syndromes. Functional phenotyping in human sensory neurons will be combined with gene expression analyses and electrophysiological data (Patch-Seq, single-cell long-read sequencing, microneurography). This multidisciplinary approach will enable a more holistic understanding of chronic pain, factoring in genetic and sex differences that are often overlooked in traditional models 10,11. The overarching objective of this project is to develop a deeper understanding of the neuroscience of chronic pain, focusing on the molecular and functional mechanisms of pain in human sensory neurons. Specific goals include: 1) Identify pain-relevant neuronal subtypes: apply Patch-seq and long-read sequencing to human sensory neurons and identify markers for pain-associated neuronal types. 2) Advance in vitro techniques for neuronal subtype detection: Use of microneurography-designed stimulation paradigms and gene expression data to develop tools for in vitro pain-neuron subtype detection.3) Develop novel interventions: Create and validate therapeutic strategies based on identified biomarkers and neuronal subtypes, using human microneurography for clinical validation. 4) Bridge basic and clinical research: Integrate preclinical data (Patch-seq, long-read sequencing) with clinical data (microneurography) to accelerate the translation of research into personalized pain management strategies.