Contact information
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Publications
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OXION
Ion Channel Initiative
Research groups
Colleges
Research spotlights
The Economist - The discovery of a gene for chronic pain could heral new treatments
The Future with Hannah Fry - Pain (Bloomberg)
Scientific commentaries:
Directional sensitivity of C-low threshold mechanoreceptors
Pain management by chemogenetic control of sensory neurons
Protecting against summation of pain
Steven Middleton
Postdoctoral Research Scientist
- Research Fellow, Wolfson College
Biography
I received my BSc (Hons) in Neuroscience from Cardiff University, my research focused on the peripheral nervous system and sensory neuron development with Professor Alun Davies. I completed a research training year at the Max Delbrück Centre for Molecular Medicine, in Berlin. I worked under the supervision of Professor Gary Lewin studing mechanisms of touch sensation. My doctoral training was completed at the University of Oxford. My Wellcome Trust DPhil Studentship investigated the role of Ion Channels in Health & Disease (OXION) with a focus on chronic pain. During my DPhil I received training from the Neural Injury Group (Oxford), the Max Delbrück Centre for Molecular Medicine (Berlin) and the University of New England (Maine, US).
I am currently a post-doctoral research scientist in the Neural Injury Research Group led by Professor David Bennett, and Research Fellow at Wolfson College.
Research Summary
My research focuses on the neurobiology of pain and touch sensation. In particular, my work interrogates the functional role of different populations of sensory neurons. Sensory neurons are heterogeneous nerve cells that innervate sensory targets such as the skin and muscle, and extend central terminals which enter the dorsal horn of the spinal cord. I study this sensory circuit and aim to understand the mechanisms that govern normal (protective) pain, and how following injury or disease pain can become chronic.
My research has two avenues;
- Discovery research: I am interested in understanding how native ion channels, membrane transporters and partner proteins function in the sensory nervous system (such as Nav1.7, NCX3, SLC45A4), particularly in the context of touch, nociception and chronic pain. Understanding the role of these proteins may offer exciting opportiunities to develop novel therapeutics for chronic pain.
- Biological engineering and gene therapies: I use and develop non-native designer ion channels and target the them to sensory neurons, to silence chronic pain at the source. These engineered ion channels, function as an off-switch in pain transmission. I am developing these tools as innovative gene therapies that can silence overactive pain signals as a means to treat chronic pain.
To investigate these questions my research uses a wide range techniques including: Histology, molecular biology, gene-therapy design, viral construct design, chemogenetic silencing, human cellular models of chronic pain, patch-clamp electrophysiology and skin-nerve primary afferent recordings.
Key publications
SLC45A4 is a pain gene encoding a neuronal polyamine transporter
Journal article
Middleton SJ. et al, (2025), Nature, 646, 404 - 412
A humanized chemogenetic system inhibits murine pain-related behavior and hyperactivity in human sensory neurons
Journal article
Perez-Sanchez J. et al, (2023), Science Translational Medicine, 15
Nav1.7 is required for normal C-low threshold mechanoreceptor function in humans and mice
Journal article
Middleton SJ. et al, (2022), Brain, 145, 3637 - 3653
Sodium-calcium exchanger-3 regulates pain “wind-up”: From human psychophysics to spinal mechanisms
Journal article
Trendafilova T. et al, (2022), Neuron, 110, 2571 - 2587.e13
Studying human nociceptors: from fundamentals to clinic
Journal article
Middleton SJ. et al, (2021), Brain, 144, 1312 - 1335
Using an engineered glutamate-gated chloride channel to silence sensory neurons and treat neuropathic pain at the source
Journal article
Weir GA. et al, (2017), Brain, 140, 2570 - 2585
Recent publications
Understanding sensory abnormalities in fibromyalgia through autoantibodies
Journal article
Themistocleous AC. et al, (2025), Brain, 148, 3792 - 3794
SLC45A4 is a pain gene encoding a neuronal polyamine transporter
Journal article
Middleton SJ. et al, (2025), Nature, 646, 404 - 412
Specific overexpression of contactin-associated protein-like 2 and its effects on pain-related behaviour in mice
Journal article
Tseng M. et al, (2025), PAIN Reports, 10, e1309 - e1309
In vivo calcium imaging reveals directional sensitivity of C‐low threshold mechanoreceptors
Journal article
Semizoglou E. et al, (2025), The Journal of Physiology, 603, 895 - 908
Identification of SLC45A4 as a pain gene encoding a neuronal polyamine transporter
Preprint
Middleton SJ. et al, (2024)
Characterising the stimulus-response function of mouse C-Low threshold mechanoreceptors to mechanical stimuli in vivo
Preprint
Semizoglou E. et al, (2024)
GluCl.CreON enables selective inhibition of molecularly defined pain circuits
Journal article
Middleton SJ. et al, (2023), Pain, 164, 2780 - 2791
A humanized chemogenetic system inhibits murine pain-related behavior and hyperactivity in human sensory neurons
Journal article
Perez-Sanchez J. et al, (2023), Science Translational Medicine, 15
Long-term tactile hypersensitivity after nerve crush injury in mice is characterized by the persistence of intact sensory axons
Journal article
Kim HW. et al, (2023), Pain, 164, 2327 - 2342
Inhibition of sensory neuron driven acute, inflammatory, and neuropathic pain using a humanised chemogenetic system
Journal article
Perez-Sanchez J. et al, (2023)