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One putative function of SGCs is to regulate the neuronal microenvironment, but this role has received only little attention. In this study we investigated whether the SGC envelope serves a barrier function and how SGCs may control the neuronal microenvironment. We studied this question on short\u2010term (&lt;24\u2009h) cell cultures of dorsal root ganglia and trigeminal ganglia from adult mice, which contain neurons surrounded with SGCs, and neurons that are not. Using calcium imaging, we measured neuronal responses to molecules with established actions on sensory neurons. We found that neurons surrounded by SGCs had a smaller response to molecules such as adenosine triphosphate (ATP), glutamate, GABA, and bradykinin than neurons without glial cover. When we inhibited the activity of NTPDases, which hydrolyze the ATP, and also when we inhibited the glutamate and GABA transporters on SGCs, this difference in the neuronal response was no longer observed. 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