In this paper we surveyed somatosensory neurons by in vivo calcium imaging in rat model of bone cancer.
Skeletal metastases are frequently accompanied by chronic pain that is mechanoceptive in nature. Mechanistically, cancer induced bone pain (CIBP) is transmitted from the cancerous site to central domains via peripheral neurons, the cell bodies of which are housed in the dorsal root ganglia (DRG). How these somatosensory neurons encode different sensory information remains only partly explained.
We have taken advantage of recent advances in genetically-encoded calcium indicators (virally expressed GCaMP6s) and imaging technologies to enable for the first time, in vivo recording of hundreds of sensory neurones simultaneously in the rat DRG to study ‘population coding’ of mechanical forces.
We utilised Markov Clustering Analysis of calcium responses to reveal clusters of primary afferents responding distinctively to mechanical forces applied to the peripheral receptive field. We suggest that this type of analysis can be utilised for largely unsupervised clustering of functional neuronal data. Next, we characterised the nerves that respond to mechanical compression of the bone. We showed that under conditions of bone cancer a distinct population of nociceptors are recruited; utilising neuronal tracing we found that the mechanism appears to be activation of silent nociceptors surrounding the tumour.