A pilot imaging mass cytometry study of cutaneous nerve-immune cell interactions in post-herpetic neuralgia

Post-herpetic neuralgia (PHN) is a chronic pain condition that persists after shingles and involves dermatome-specific allodynia, disability, and psychological comorbidities. Cutaneous neuroimmune dysregulation is increasingly linked to chronic pain, but the mechanisms underlying PHN remain unclear. This study is the first high-parameter imaging analysis of PHN-affected skin using imaging mass cytometry (IMC). Skin biopsies from PHN-affected dermatomes (n = 6) and healthy controls (n = 6) were stained with a 13-marker antibody panel targeting immune cells and nerve fibres. Immune cell densities and their spatial proximity to nerve fibres were quantified in a customised analysis pipeline. Langerhans cell density and skin-homing memory T cells were elevated in PHN-affected skin. There were trends towards higher T cells, infiltrating T helper type 1-like T cells, and T cell-nerve fibre interactions. While overall macrophage and DC subset numbers were unchanged, anti-inflammatory macrophage-nerve fibre interactions were significantly increased, but decreased across both DC subsets, suggesting selective spatial reorganisation of myeloid cell populations in the nerve fibre microenvironment. Nerve fibre density itself was unchanged. These findings suggest that persistent neuroimmune alterations may be involved in PHN pathophysiology. Our pilot study highlights the potential of IMC to reveal previously unrecognised cutaneous pathomechanisms that may contribute to PHN. Future IMC studies with larger sample sizes should be undertaken to guide the development of novel therapeutic strategies for PHN.