Glutamatergic transmission through NMDA receptors (NMDARs) is important for the function of peripheral tissues. In the bone, NMDARs and its co-agonist, D-serine participate in all the phases of the remodeling. In the vasculature, NMDARs exerts a tonic vasodilation decreasing blood perfusion in the corpus cavernosum and the filtration rate in the renal glomerulus. NMDARs are relevant for the skin turnover regulating the proliferation and differentiation of keratinocytes and the formation of the cornified envelope (CE). The interference with NMDAR function in the skin leads to a slow turnover and repair. As occurs with the brain and cognitive functions, the manifestations of a hypofunction of NMDARs resembles those observed during aging. This raises the question if the deterioration of the glomerular vasculature, the bone remodeling and the skin turnover associated with age could be related with a hypofunction of NMDARs. Furthermore, the interference of D-serine and the effects of its supplementation on these tissues, suggest that a decrease of D-serine could account for this hypofunction pointing out D-serine as a potential therapeutic target to reduce or even prevent the detriment of the peripheral tissue associated with aging.

Astrocytes are determinants for the functioning of the CNS. They respond to neuronal activity with calcium increases and can in turn modulate synaptic transmission, brain plasticity as well as cognitive processes. Astrocytes display sensory-evoked calcium responses in different brain structures related to the discriminative system of most sensory modalities. In particular, noxious stimulation evoked calcium responses in astrocytes in the spinal cord, the hippocampus, and the somatosensory cortex. However, it is not clear if astrocytes are involved in pain. Pain is a private, personal, and complex experience that warns us about potential tissue damage. It is a perception that is not linearly associated with the amount of tissue damage or nociception; instead, it is constructed with sensory, cognitive, and affective components and depends on our previous experiences. However, it is not fully understood how pain is created from nociception. In this perspective article, we provide an overview of the mechanisms and neuronal networks that underlie the perception of pain. Then we proposed that coherent activity of astrocytes in the spinal cord and pain-related brain areas could be important in binding sensory, affective, and cognitive information on a slower time scale.