I am currently curating a Special Issue for MDPI Cells
on “Molecular Mechanisms Underlying Inflammatory Pain.”

If you are working on, or planning a suitable manuscript, I would be delighted if you would consider submitting it to our issue.

mdpi.com/journal/cell...

A new academic year! 🍏
 
Proud to watch my Pegasus Scholars students presenting on targeted cancer therapies today, after a week exploring the formation, functions, faults and fixing of proteins! 🔬
 
Glad to support Robinson College’s excellent widening participation initiation for another year! 👨‍🏫

Still got it! ⚡️

🤩 geeking out at Geneva light festival last weekend - double helix 🧬 & neuron 🧠 #genevalux

Taken together, we postulate that GPR65 on FLS orchestrates inflammatory joint pain through the release of mediators and subsequent crosstalk between neurons and immune cells. Thus inhibiting GPR65 might represent a means of relieving inflammatory pain. 🧵[9/10]

Increased expression of GPR65 has previously been reported in human osteoarthritis (OA). BTB also stimulated increases in pro-inflammatory cytokine production by FLS isolated from human OA patients. Further, synovial fluid samples from OA patients could activate GPR65. 🧵[8/10]

The role of GPR65 was confirmed by the inability of BTB to increase inflammatory mediator secretion by GPR65 knockout (KO) FLS, and lack of inflammation and pain-like behaviours when GPR65 KO mice were injected with BTB. 🧵[7/10]

…suggesting another cell type might be involved. Fibroblast-like synoviocytes (FLS), which line the knee joint, express GPR65. Stimulating FLS with BTB increased secretion of inflammatory cytokines, which could increase the excitability of naïve neurons. 🧵[6/10]

To investigate the cellular basis of the pain-like behaviours seen in mice, we explored whether BTB increased neuronal excitability. While neurons isolated from BTB-injected mice were hyperexcitable, we could not recreate this by incubating naïve neurons with BTB alone… 🧵[5/10]

Next, we injected BTB to the knee joint of mice. This caused both inflammation and an increase in pain-like behaviours, suggesting that activation of GPR65 in the knee joint is sufficient to drive inflammatory pain. 🧵[4/10]

…So, we first compared the signalling signatures of protons, BTB and psychosine (all reported to activate GPR65). We found that BTB recapitulated most features of proton-mediated signalling. Importantly, BTB was also shown to only activate GPR65 over other PS-GPCRs. 🧵[3/10]

Inflammatory conditions, like arthritis, are both painful and associated with acidosis. Thus we investigated if acidosis drives pain through GPR65 (a proton-sensing GPCR) - this isn’t an easy task though, as there are lots of receptors that can be activated by protons… 🧵 [2/10]