Models and Mechanisms of Trigeminal Neuralgia

Professor Michael Gold PhD, Professor of Neurobiology, University of Pittsburgh

Trigeminal neuralgia (TN), also known as the suicide disease, is a chronic pain disorder with unique signs and symptoms that have never been successfully reproduced in an animal model. TN is characterized by recurrent severe unilateral brief electric shock-like pains, lasting a fraction of a second to 2 minutes that are triggered by innocuous stimuli ¹. The clinical features of TN have been used with varying degrees of success to guide the most recent attempts to generate preclinical models. While the validation of these models is ongoing, emerging evidence suggests that the signs and symptoms of this devesting disorder may not only be due to the unique site of injury, but differences between trigeminal and somatic nerves ^2-4. These differences include both gene expression patterns in the absence of injury, as well as changes in gene expression in response to injury. Several of these differentially expressed genes appear to be critical for action potential propagation in trigeminal nerves. Dr. Gold will discuss these issues in the context of recent findings from his laboratory.

1. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38(1):1-211. Epub 2018/01/26. doi: 10.1177/0333102417738202. PubMed PMID: 29368949.
2. Pineda-Farias JB, Loeza-Alcocer E, Nagarajan V, Gold MS, Sekula RF, Jr. Mechanisms Underlying the Selective Therapeutic Efficacy of Carbamazepine for Attenuation of Trigeminal Nerve Injury Pain. J Neurosci. 2021;41(43):8991-9007. Epub 2021/08/28. doi: 10.1523/jneurosci.0547-21.2021. PubMed PMID: 34446571; PMCID: PMC8549540.
3. Korczeniewska OA, Husain S, Khan J, Eliav E, Soteropoulos P, Benoliel R. Differential gene expression in trigeminal ganglia of male and female rats following chronic constriction of the infraorbital nerve. Eur J Pain. 2018;22(5):875-88. Epub 2018/01/20. doi: 10.1002/ejp.1174. PubMed PMID: 29350446.
4. Korczeniewska OA, Katzmann Rider G, Gajra S, Narra V, Ramavajla V, Chang YJ, Tao Y, Soteropoulos P, Husain S, Khan J, Eliav E, Benoliel R. Differential gene expression changes in the dorsal root versus trigeminal ganglia following peripheral nerve injury in rats. Eur J Pain. 2020;24(5):967-82. Epub 2020/02/27. doi: 10.1002/ejp.1546. PubMed PMID: 32100907.

Assays with Relevance to Pain Drug Discovery

Anthony M. Rush PhD, Director of Neuroscience, Metrion Biosciences

Well designed and relevant pain drug discovery assays are essential tools in the identification, validation and development of novel therapeutics for pain management. These assays aim to assess the efficacy, safety and mechanism of action of potential pain relieving compounds. Examples of these approaches will be presented, including translational assays using sensory neurons, which can be deployed to assist in progressing drug candidates with a higher likelihood of success towards clinical use.

Professor Michael Gold PhD

Professor of Neurobiology, University of Pittsburgh

Michael S. Gold, Ph.D., is a Professor of Neurobiology at the University of Pittsburgh. Dr. Gold received his B.A. from UC Berkeley, Ph.D. from UCLA, and was postdoctoral fellow with Jon Levine at USCF. The focus of Dr. Gold’s research is the neurobiology of pain. He has made important contributions to injury-induced plasticity in nociceptive afferents, and their contribution to the manifestation of persistent pain. Toward this end, he has employed an array of approaches ranging from the study of isolated cells to the development of novel behavioral assays with which to assess the presence of persistent hypersensitivity, and more recently the study of clinical populations suffering from persistent pain. Dr. Gold is actively involved in the greater pain community most recently working to form the US Association for the Study of Pain.

Anthony M. Rush PhD

Director of Neuroscience, Metrion Biosciences

Tony has been in the ion channel field for over 25 years across academia and industry and is widely published. He received his PhD from the University of Dundee (UK) characterising sodium channels of DRG neurons related to pain using the patch-clamp technique. He then studied hippocampal synaptic plasticity at Trinity College Dublin (Ireland), before continuing sodium channel research with Stephen Waxman at Yale University (USA).

Subsequently, Tony co-ordinated ion channel contracts at NeuroSolutions Ltd (UK) for clients in the biotechnology and pharmaceutical industries before moving to AstraZeneca (Sweden) to work on preclinical pain targets, where he was the lead biologist for a number of ion channel programmes.

Tony returned to the UK working on ion channel screening projects and translational assays with external parties at Xention Ltd (UK), before becoming a founding team member at Metrion. His responsibilities include leading the team on a FTE-based collaborative drug discovery project with a pharma client and leading neuroscience activities across the company.

Connect with Tony on LinkedIn.