Gatto, Graziana - C 06

Diabetes mellitus is a metabolic disorder characterized by persistent hyperglycemia and is among the leading causes of global morbidity and mortality. One of its most debilitating complications is diabetic neuropathy, which culminates in chronic pain and severely compromises patient’s quality of life. Despite its clinical significance, the pathophysiological mechanisms underlying the onset of neuropathic pain in diabetes remain poorly understood. As a result, current treatment strategies are largely limited to lifestyle interventions and symptomatic pain management. 

Although diabetic neuropathies present with diverse clinical manifestations, they all affect peripheral sensory neurons in the dorsal root ganglia. Patients paradoxically experience chronic pain alongside sensory perception loss. Using a mouse model of type 2 diabetes, we showed that tactile perception loss begins during the pre-diabetic phase and precedes the onset of chronic pain. These findings suggest that the early, prodromal changes in sensory neurons prime the sensory-spinal circuits for the development of chronic pain. 

Building on these findings, we will state-of-the-art behavioral assays with intersectional genetic and proteomic approaches to identify early markers of vulnerability to hyperglycemia at single neuron type resolution. Identifying these prodromal markers will enable targeted restoration of function in specific neuronal populations using chemogenetic and/or pharmacological strategies. Collectively, these studies will define early disease markers and uncover novel therapeutic targets for the prevention and treatment of diabetic neuropathy.

Despite its substantial health burden, there are currently no disease-modifying therapies for diabetes-induced neuropathic pain beyond lifestyle modification, glycemic control, and symptomatic pain relief. Identifying early molecular changes in defined neuronal populations is therefore of high translational relevance, as it could enable earlier diagnosis, inform the development of preventive strategies, and open new avenues for curative rather than purely palliative treatments for diabetic chronic pain.

• Intersectional genetics (Gatto et al. 2021; Yao et al. 2025; Hayashi et al. 2023)
• Mouse Behavior (Gatto et al. 2021; Yao et al. 2025; Hayashi et al. 2023)
• Chemogenetics/Optogenetics (Gatto et al. 2021; Yao et al. 2025; Koch et al. 2017)
• EMG recordings (Chung et al. 2023; Hayashi et al. 2023)
• Neuron connectivity (AAVs- and rabies-based approaches)(Gatto et al. 2021)
• Biomechanical modeling (Yao et al. 2025)

For more research information, please check Gatto Lab. 

• Center for Molecular Medicine Cologne (CMMC)
• Dept. of Neurology, Faculty of Medicine, University Hospital Cologne, Germany