English: Comprehensive overview of pathophysiology of trigeminal postherpetic neuralgia (TG-PHN). A VZV reactivation predominately occurs from V1 distribution of the trigeminal ganglia. B Representation of cellular response at the site of reactivation highlighting the (1) inflammatory response involving macrophages, T cells, mast cells, and blood vessels; (2) changes in trigeminal afferents, particularly alterations in nociceptors influencing pain signaling such as TRVP1/TRPA1, CGRP, NK-1R, and purinergic receptors P2XR, along with associated ligands like substance P (SubP) and CGRP, ultimately resulting in (3) loss of nerve fibers and sensory innervation. C Representation of VZV reactivation and (4) viral replication of VZV and associated inflammation in the trigeminal ganglia. This leads to (5) cell death and can cause (6) hypersensitivity in the ganglionic neurons, increasing pain signals to the brainstem. Hypersensitivity can also be attributed to increases in neurotransmitters CGRP, SubP, and ATP. D Trigeminal ganglionic neurons transmit signals to the spinal trigeminal ganglia, specifically the caudal subunit (SNVc), which transmits nociception and thermal sensation. Neuroinflammation, including (8) astrogliosis and microglia activation, can cause disruption in the microenvironment within the brainstem. The increase of neurotransmitters, shown in C, is also released onto second-order neurons. Along with a decrease in inhibitory GABAergic signaling, together leads to (9) an increase in pain signaling. E Represents the pain signaling pathway from SNVc to the ventral posteromedial nucleus (VPM), where it has been shown to decrease GABAergic signaling in the thalamus, increasing pain signaling relayed to cortical structures. F These pathophysiological changes ultimately lead to the wide array of pain qualities associated with TG-PHN as represented in this artistic depiction reprinted with permission from Ref. [26]. Figure 1 was created with BioRender.com