Linking sensory physiology to transcriptomics to understand human chronic pain

Rapid progress in human transcriptome sequencing has provided information about the molecular expression of dorsal root ganglia neurons in the somatosensory system. However, functional evaluation lags far behind.

We propose to build on our previous study in healthy humans integrating results from single-cell in vivo microneurography recordings with RNA sequencing and proceed to study migraine patients.

Migraine is a chronic pain disorder with a strong genetic component and characterized by intense, debilitating headache, often coupled with nausea, vomiting, and somatosensory hypersensitivity.We have developed novel methods for ultrasound-guided microneurography, and quantification of complex afferent response properties making single-cell in vivo microneurography recordings suitable for patient examinations and functional evaluation of human RNA-seq.

Behavioral and microneurography findings in migraine patients and control subjects will be combined with results from single-soma deep RNA-seq of neurons of trigeminal ganglia, from migraine and control donors, provided by our collaborators at the Univ of Pennsylvania, USA.Our proposed study will generate unprecedented multi-dimensional molecular and functional datasets at normal conditions and in migraine, which will elucidate mechanisms underlying chronic pain.

Our results may lead to the discovery of new biomarkers for chronic pain and the identification of novel treatment targets.