Investigation of cellular and molecular changes linked with neuropathic pain in healthy and injured human trigeminal nerves

Abstract Injuries to the trigeminal nerve, responsible for sensory innervation to the face, may occur during routine dental procedures, resulting in the formation of a neuroma accompanied by loss of sensation and/or symptoms of pain. In order to gain insight into the molecular mechanisms underpinning the sensory changes, single nuclei RNA sequencing and spatial transcriptomics were employed to profile the transcriptional landscape at single cell resolution of human trigeminal nerves and neuromas. Cellular and transcriptional changes were identified that correlated with the presence of pain, including an expansion of endothelial cells with a pro-inflammatory phenotype and over-expression of HLA-A , CXCL2 and CXCL8 . Interactome analysis highlighted signalling changes linked with the presence of pain. HLA-A protein expression was confirmed in neuromas and positively correlated with symptoms of pain. The atlas generated represents a valuable resource for pain research, highlighting the role of inflammation, endothelial cell dysfunction and chemokine signalling in neuropathic pain.