Non-neuronal cells act as crucial players in neuropathic orofacial pain

Background: Following peripheral nerve damage, various non-neuronal cells are activated, triggering accumulation in the peripheral and central nervous systems, and communicate with neurons. Evidence suggest that neuronal and non-neuronal cell communication is a critical mechanism of neuropathic pain; however, its detailed mechanisms in contributing to neuropathic orofacial pain development remain unclear. Highlight: Neuronal and non-neuronal cell communication in the trigeminal ganglion (TG) is believed to cause neuronal hyperactivation following trigeminal nerve damage, resulting in neuropathic orofacial pain. Trigeminal nerve damage activates and accumulates non-neuronal cells, such as satellite cells and macrophages in the TG and microglia, astrocytes, and oligodendrocytes in the trigeminal spinal subnucleus caudalis (Vc) and upper cervical spinal cord (C1–C2). These non-neuronal cells release various molecules, contributing to the hyperactivation of TG, Vc, and C1–C2 nociceptive neurons. These hyperactive nociceptive neurons release molecules that enhance non-neuronal cell activation. This neuron and non-neuronal cell crosstalk causes hyperactivation of nociceptive neurons in the TG, Vc, and C1–C2. Here, we addressed previous and recent data on the contribution of neuronal and non-neuronal cell communication and its involvement in neuropathic orofacial pain development. Conclusion: Previous and recent data suggest that neuronal and non-neuronal cell communication in the TG, Vc, and C1–C2 is a key mechanism that causes neuropathic orofacial pain associated with trigeminal nerve damage.