Neurophysiology
Our group explores the physiological aspects of pain by using in vitro models including induced stem cell-derived neurons. Our studies focus on ion channel functioning and their regulation by G-protein coupled receptors by using a set of physiological, biophysical and molecular techniques. The aim of our studies is to provide rational basis for the new therapeutic approaches for functional rescue of impaired neurons at persistent orofacial pain and associated comorbidities, i.e. neurodegeneration, inflammation and ageing.
Investigation of Calcium-sensing Receptor and Voltage-gated Potassium Channel Type 7 Crosstalk: A Potential Therapeutic Target for Persistent Neuropathic Orofacial Pain
Recently we discovered that calcium-sensing receptor (CaSR) regulates activity of voltage-gated potassium channel type 7 (Kv7 channel) by using in vitro models. PhD thesis of Nontawat Chuinsiri and a research manuscript can be found here https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.16349.
This study demonstrated that CaSR-Kv7.2/7.3 channel crosslink effectively regulates neuronal excitability providing a feasible pharmacological target for neuronal hyperexcitability management in neuropathic pain.
The new project is a logical continuation of our original discovery, we aspire to define the significance of CaSR as a therapeutic target in mechanisms leading to the development and maintenance of neuropathic pain Clinically this is highly important as most of the work on pain pathways has to date been carried out at the spinal cord level with an assumption that equivalent processes occur at the level of sensory ganglia (e.g. dorsal root and trigeminal ganglia). Therefore, our work is going to develop a better understanding of neuropathy mechanisms and suggest novel therapeutic strategies for the chronic pain management and possibly specific co-morbidities.
Exploring peripheral trigeminal voltage gated sodium channel commonalities in Parkinson’s disease and orofacial neuropathic pain to identify areas for therapeutic exploitation
Persistent neuropathic pain (NP) could be a co-morbidity for neurodegenerative conditions i.e. Parkinson’s disease (PD) associated with abnormally high excitability due to excitotoxicity and consequent neuronal damage. Emma Beecroft is currently a PhD student on the project (co-supervisors on the project Justin Durham and Ilona Obara).
Investigation of effects of PKCδ inhibitor rottlerin in neuropathic pain management
Rottlerin (mallotoxin), a potent inhibitor of protein kinase C delta (PKCδ), is a natural polyphenol compound isolated from the Asian Kamala plant Mallotus Philippinensis that is known to have a diverse pharmacology spectrum. Rottlerin was shown to display anti-tumor, anti-oxidative, anti-inflammatory and anti-proliferative effects and it can act as a potential neuroprotective compound. In addition, rottlerin has low toxicity profile and exhibits semi-protective effects on cells and tissues. Thus, rottlerin may offer an innovative and efficient strategy to control neuropathic pain (NP) including dental and orofacial pain.
Investigating effects of chronic hyperglycaemia on transmembrane current in retinal Müller cells
Muller cells are the key glial cells in human retina responsible for maintaining its fluid transport and homeostasis. Hyperglycaemia induces dysfunction, swelling and death of Muller cells leading to diabetic retinopathy. Diabetic retinopathy is associated with dysfunction of retinal Müller cell glia, resulting in retinal oedema, neuronal death, and may ultimately lead to permanent blindness. We are investigating potential of pharmacological regulation of transmembrane cation conductance to provide a novel therapeutic strategy in rescuing from diabetic macular oedema and preventing blindness.