Drug Delivery Systems for Advanced Treatment of Pain and Inflammation
thesisposted on 06.05.2022, 00:59 by JEFFRI STEVENS RETAMAL SANTIBANEZ
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 The main project of this thesis is an unpublished chapter studying the role of mGlu5 endocytosis for pain transmission.