a1 Laboratory of Molecular and Cellular, Pharmacology of Purinergic Transmission, Department of Pharmacological Sciences, Università degli Studi di Milano, Milan, Italy
a2 CNR Institute of Neuroscience, Department of Medical Pharmacology – Università degli Studi di Milano, Milan, Italy
The role of adenosine-5′-triphosphate (ATP) and of the ligand-gated P2X3 receptor in neuronal dorsal root ganglia (DRG) pain transmission is relatively well established. Much less is known about the purinergic system in trigeminal ganglia (TG), which are involved in certain types of untreatable neuropathic and inflammatory pain, as well as in migraine. Emerging data suggest that purinergic metabotropic P2Y receptors on both neurons and satellite glial cells (SGCs) may also participate in both physiological and pathological pain development. Here, we provide an updated literature review on the role of purinergic signaling in sensory ganglia, with special emphasis on P2Y receptors on SGCs. We also provide new original data showing a time-dependent downregulation of P2Y2 and P2Y4 receptor expression and function in purified SGCs cultures from TG, in comparison with primary mixed neuron–SGCs cultures. These data highlight the importance of the neuron–glia cross-talk in determining the SGCs phenotype. Finally, we show that, in mixed TG cultures, both adenine and guanosine induce intracellular calcium transients in neurons but not in SGCs, suggesting that also these purinergic-related molecules can participate in pain signaling. These findings may have relevant implications for the development of new therapeutic strategies for chronic pain treatment.
c1 Correspondence should be addressed to: Maria P. Abbracchio, Department of Pharmacological Sciences, Università degli Studi di Milano, via Balzaretti, 9-20133 Milan, Italy phone: +39-0250318304 email: firstname.lastname@example.org
* These authors contributed equally to this work.