Figure 2.

Satellite glial cells (SGCs) surrounding the cell bodies of neurons in the ganglia play an important role in the development of neuropathic pain. Nerve injury leads to the activation and proliferation of SGCs in the sensory ganglia. They interact with neurons through paracrine signaling. ATP, released from SGCs as well as from injured neurons, acts on purinergic receptors, resulting in the mutual activation of neurons and SGCs (indicated in the diagram by straight arrows). Purinergic receptors, P2Y12 and P2X3, are upregulated in the trigeminal ganglion following nerve injury. SGCs express the inwardly rectifying potassium channel, Kir4.1, which helps to maintain extracellular potassium homeostasis. Following nerve injury, expression of Kir4.1 is downregulated in the trigeminal ganglion, thereby increasing extracellular potassium and neuronal excitability. Communication among the SGCs also increases (indicated in the diagram by solid curved arrows), as evidenced by the increase in expression of the common gap junction protein, connexin 43 (Cx43), in the trigeminal ganglion following nerve injury. This communication spreads to the SGCs of nearby neurons, which in turn sensitizes these cells. ATP: Adenosine triphosphate; P2Y12: Purinergic receptor subtype Y12; P2X3: Purinergic receptor subtype X3; Kir4.1: Inwardly rectifying potassium (Kir) channel 4.1. TG: Trigeminal ganglion.