Oro-cranio-facial pain remains a particular clinical challenge, the “grand challenge” of pain medicine from the perspective of the presenter. This is so because of the enormously devastating emotional impact that this form of pain has on those who are tormented by it. The retrospective clinical insights of the presenter, now providing care for patients with oro-cranio-facial pain and trigeminal pain/sensory disorders for >12y, will be referenced with particular attention to this aspect of the pain. Clinical findings will be reviewed against a background of a novel neural circuit that was recently characterized as providing a direct connection from trigeminal ganglion to emotional processing centers and integration hubs for instinctive behaviors. Next, the presenter will share some of his experiences with topically delivered treatments, botulinum toxin, high-% transdermally applied capsaicin, high skin-penetrating ketoprofen and menthol. The clinical treatment profile of these approaches will be highlighted against their molecular and neural circuit mechanism of action, with particular focus on transient receptor potential (TRP) ion channels. TRPA1, TRPM8, TRPV1 and TRPV4 will be discussed more in depth pertaining to their role as pain-TRPs, also itch-TRPs. Re the latter, molecular and neural circuit pathophysiology of TRPV4 will be introduced.

Objectives
– retrospective clinical assessment of emotional toll of oro-cranio-facial pain disorders
– establishing key concepts of a novel neural circuits, proper to the trigeminal system, that underlies emotional pain processing
– retrospective clinical assessment of helpful topical treatments that target peripheral trigeminal nerve endings and their respective molecular machinery
– highlighting mechanisms of action of botulinum toxin, high-% capsaicin, high-skin penetration ketoprofen and menthol, on trigeminally-mediated pain and itch
– establishing pathomechanisms of pain-TRPs and itch-TRPs in the trigeminal system in terms of molecular transduction and neural circuit mechanisms

I was educated in my native Germany, going through medical school (MD University of Cologne) and obtaining a PhD in Medical Virology (University of Bochum). My German residency training in neurology and psychiatry was followed by a neuropathology fellowship at Albert Einstein College of Medicine. Thereafter, I joined Jeff Friedman’s Laboratory at Rockefeller University, became Assistant Professor, then took my first independent faculty position at Duke (2004). I am a scientist-physician with active professional agendas in both worlds, with my focus on trigeminal nerve pain and sensory disorders. My clinical referrals are supra-regional from the entire US. As laboratory-based scientist, I am dedicated to elucidation of transduction mechanisms of transient receptor potential (TRP) ion channels in pain, pruritus, inflammation and injury. I discovered the TRPV4 ion channel in 2000 and elucidated its role since then. I also found key roles of the astrocyte structural protein, GFAP, and how inhibitory neurotransmission can be corrupted by transcriptional dys-regulation of a chloride transporter gene, KCC2.
I harbor confidence in the concept of TRPV4 channels as a rational therapeutic target for neuropathic pain and inflammatory disorders. Leveraging this concept as a translational direction, my lab has developed small molecule dual-inhibitors for TRPV4/TRPA1. Based on this discovery, I have founded “TRPblue”, a Durham-based biotechnology start-up.
I was selected as Klingenstein Fellow in Neurosciences when joining Duke, and a Harrington Discovery Institute Scholar-Innovator when receiving tenure. Within Duke, I was selected a Broad Neuroscience Faculty Scholar and a Chancellor’s Discovery Fund Awardee.