The role of spinal astrocytes in nociception and pain

Astrocytes are a heterogeneous population of star-shaped cells, which are present in all parts of the central nervous system. Historically, they have been regarded as support cells, e.g. providing essential nutrients for nerve cells. This view has changed dramatically over recent years and it has now become evident that astrocytes exert far more complex functions than previously thought. Astrocytes might influence the transmission of information at the contact sites between nerve cells (synapses), e.g. by releasing substances that can act on respective receptors present on other nerve cells. By doing so, they might be involved in the regulation of diverse aspects of behaviour. At the spinal cord level, astrocytes might be involved in processes that underlie the transition from acute to chronic pain. However, previous evidence was indirect at best, mainly due to a lack of tools that allowed to selectively target spinal cord astrocytes experimentally. Now, a method has become available which could help to overcome this problem: novel engineered G-protein coupled receptors known as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), which can be targeted to astrocytes and can exclusively be activated by a certain compound (clozapine-N-oxide), which is not produced in the body and cannot act on other, endogenous structures. Using this method, our pilot studies revealed that the selective activation of spinal cord astrocytes indeed induces long-lasting pain hypersensitivity in adult rats. The underlying mechanisms are, however, largely unknown. Taking advantage of DREADDs, we would like to study the impact of selective astrocyte activation at the spinal cord level on pain-related behaviour and investigate the cellular and synaptic processes involved. Thereby, our study can lead to a better understanding of the role of astrocytes in the generation of pathological pain states, thus providing a basis for the development of novel astrocyte- directed pain treatments.