Chair: Mateusz Kucharczyk (Łukasiewicz – PORT, Wroclaw, Poland)

Symposium 3: Novel approaches for the PNS targeting and modulation

This symposium highlights cutting-edge methods for PNS-targeted pain and cancer control. Showcasing opto-/chemogenetics, novel imaging, and electrophysiological methods, it provides actionable insights into detailed PNS recording and modulation. Designed for researchers and clinicians seeking new perspectives on targeting the peripheral nervous system to develop innovative therapeutic strategies.


Dr Mateusz Kucharczyk, Polish Centre for Technology Development, Łukasiewicz-PORT, Wrocław, Poland

Somatosensation and Cancer Neuroscience

Dr. Kucharczyk will explore the neurogenic regulation of cancer and associated pain, focusing on the role of peptidergic and silent nociceptors in cancer-induced bone pain. Using selective genetic targeting, he will showcase how these neuronal populations respond to pathological changes in cancerous tissue. Finally, he will present novel approaches for studying presynaptic modulation with fibre-type-specific functional imaging, highlighting the modulation potential of nociceptive transmission through genetically-defined spinal and descending pathways.

References:
1. Kucharczyk MW, et al. The impact of bone cancer on the peripheral encoding of mechanical pressure stimuli. Pain, 2020.
doi: 10.1097/j.pain.0000000000001880
2. Kucharczyk MW, et al. A critical brainstem relay for mediation of diffuse noxious inhibitory controls. Brain. 2023. doi: 10.1093/brain/awad002


Dr Jimena Perez-Sanchez, Neural Injury Group, University of Oxford, UK

Targeted chemogenetic inhibition of sensory afferents for pain relief in mice and humans

Dr. Perez-Sanchez will discuss her work with the PSAM4-GlyR chemogenetic system. This system uses humanized ligand-gated channels to achieve selective silencing of hyperexcitable neurons with demonstratable therapeutic potential across multiple pain conditions, including inflammatory joint and neuropathic. Her findings reveal how chemogenetic approaches can precisely control specific neuronal compartments, extending their application to study presynaptic control mechanisms and the role of resting potential differences in DRG neurons.

References:
1. Perez-Sanchez J, et al. A humanized chemogenetic system inhibits murine pain-related behavior and hyperactivity in human sensory neurons. Science Translational Medicine, 2023. doi: 10.1126/scitranslmed.adh3839


Dr George Goodwin, Wolfson Sensory, Pain, and Regeneration Centre, King’s College London, UK

Assessment of spontaneous activity and the role of silent nociceptors in musculoskeletal pain

Dr. Goodwin will discuss methods for assessing spontaneous activity in dorsal root ganglion neurons, as well as the use of a selective genetic model that enable targeted studies of silent nociceptors. His research provides new insights into how spontaneous neuronal activity underpins chronic pain states, particularly in musculoskeletal conditions with neuropathic features, such as osteoarthritis and rheumatoid arthritis.

References:
1. Ingram S, et al. Assessing spontaneous sensory neuron activity using in vivo calcium imaging. Pain, 2024. doi: 10.1097/j.pain.0000000000003116
2. Choi D, et al. Spontaneous activity in peripheral sensory nerves: a systematic review. Pain, 2024. doi: 10.1097/j.pain.0000000000003115


Dr Sara Jager, Madsen Lab, Department of Neuroscience, University of Copenhagen, Denmark

Using 3D imaging and spatial brain transcriptomics to analyze peripheral relief of neuropathic pain

Dr. Jager will focus on the application of tissue clearing and 3D imaging techniques to investigate peripheral tissues and their interactions with the nervous system during neuropathic pain. Additionally, she will highlight the integration of whole-brain cFos analysis to map the neural response in the brain to manipulation of peripheral inputs. Dr. Jager will further demonstrate how spatial brain transcriptomics enhances these analyses, offering deeper insights into the molecular underpinnings of pain processing and relief.

References:
1. Jensen KL, et al. Peripherally restricted PICK1 inhibitor mPD5 ameliorates pain behaviors in murine inflammatory and neuropathic pain models. JCI Insight., 2024. doi: 10.1172/jci.insight.170976

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