Unmasking Sex-specific roles of Astrocytes in Pain Signaling

Chronic pain is a widespread and serious health problem that affects millions of people and places a substantial burden on patients and healthcare systems worldwide. Notably, women are more frequently affected and often experience more severe forms of chronic pain than men. Recent research suggests that these differences may have biological origins, involving not only the nervous system but also immune cells and immune-competent cells such as glial cells in the brain and spinal cord. This project investigates the role of a specialized glial cell type, astrocytes, which are functionally and spatially integrated with neurons and actively contribute to the processing of sensory information within the spinal cord. Although there is compelling evidence that astrocytes are key modulators of pathological pain, the precise cellular and molecular mechanisms by which they influence synaptic communication, particularly in the context of sex-specific neurobiological differences, remain poorly understood. In this project, we aim to determine whether - and in what way - astrocytes contribute to the processing of pain-related signals at spinal nociceptive synapses in a sex-specific manner. To this end, we will apply advanced experimental techniques to selectively modulate astrocyte activity and assess the resulting effects on neuronal communication and pain-associated behavior. This will include high-resolution imaging, electrophysiological recordings, and behavioral assessments designed to investigate pain responses in a controlled setting. Furthermore, we will investigate the proteins produced and secreted by spinal astrocytes and compare male and female profiles using cutting-edge proteomic methods. Through this work, we seek to uncover fundamental biological differences in astrocyte-neuron interactions that may help explain sex-specific manifestations of painand thereby provide a scientific foundation for the development of novel, astrocyte-targeted pain therapies.