Drug Delivery Systems for Advanced Treatment of Pain and Inflammation

The main focus of this thesis is to understand how the signalling of GPCRs can influence cellular processes of relevance to pain and inflammation, in a spatiotemporal manner. Two key receptors in pain pathways, including the Neurokinin 1 Receptor and metabotropic glutamate receptor mGlu5, were investigated to assess how these GPCRs contribute to signalling when distributed to endosomes; and if endosomal signalling can be targeted to modulate pain. The thesis utilises genetic encoded biosensors, pharmacological tools and polymeric nanoparticles for location-specific drug delivery. An additional study investigated the importance of the ion channel TRPV4 as an effector protein for serotonin-induced 5HT2A receptor signalling and edema. This thesis includes 3 results chapters and 2 manuscripts published in peer reviewed journals. The main project of this thesis is an unpublished chapter studying the role of mGlu5 endocytosis for pain transmission.