Neuropathic pain – defined as pain arising from damage to the somatosensory system – affects 7-10% of the population, causing patients to experience burning or stabbing sensations even in the absence of any external stimuli. 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.
Here, the cellular and transcriptional landscape of healthy and injured human trigeminal nerves was characterised at single-cell resolution and the cell-cell communication between non-neuronal cells and trigeminal neurons was computationally inferred. The transcriptional landscape of painful and non-painful human neuromas within the tissue architecture was profiled using spatial transcriptomics and several differentially expressed genes were identified. Finally, RNAscope and immunohistochemistry were utilised to validate single nuclei RNA sequencing and spatial transcriptomics experiments.
This study characterises human trigeminal nerves at single-cell level, before and after injury, highlighting transcriptomic changes in Schwann cells and immune cells associated with injury. Differential expression analysis between painful and non-painful neuromas highlighted the role of inflammatory mediators in neuropathic pain. RNAscope and immunohistochemistry confirmed the expression of several injury- and pain-relevant molecules in the predicted cell-types.
The cellular atlas generated in this study will be of significant interest to the wider research community, reporting the expression of thousands of genes at single-cell resolution in clinically relevant human tissue in health and associated with nerve injury and pain, providing a precious resource for the development of novel pain treatments.
