Deciphering persistent orofacial pain

• Applicant: Professor Dr. Arne May
• Subject Area: Dentistry, Oral Surgery ; Human Cognitive and Systems Neuroscience
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 567303302

Pain in the 2nd and 3rd branches of the trigeminal nerve, i.e. idiopathic orofacial pain, is, in contrast to headaches, still largely ignored. Although quite common, scientific studies are rare and, accordingly, there are few pathophysiological concepts. This often leads to affected patients experiencing a lifelong odyssey, which in the worst case ends with the removal of all teeth and the pain still persisting. Persistent facial pain that is not dental-related is primarily persistent idiopathic facial pain (PIFP) and neuropathic facial pain (PTNP). PTNP is defined as pain resulting from injury to the trigeminal nervous system. Clinically, PIFP and PTNP are largely identical, and the difference lies in the detection of nerve damage (anaesthesia/hypesthesia/allodynia etc) in PTNP. The pathogenesis of PIFP is completely unknown. This will be investigated by studying PIFP and PTNP patients and healthy volunteers (n=53/group) using a combination of non-invasive peripheral (project 1) and central (project 2) approaches. The investigations are based on 2 main theses: 1) that PIFP patients and healthy individuals, in contrast to PTNP patients have, also sub-clinically, a healthy peripheral nervous system. This is examined using quantitative sensory testing (QST) and measuring intraoral blood flow before and after intraoral capsaicin stimulation (CIBD) using laser Doppler speckle. If subtle changes in CIBD and/or intraoral QST are found in some of the PIFP patients, this will make it possible to further characterize these subgroups in the second main hypothesis in direct comparison to PTNP patients and healthy controls. 2.) The second main thesis is the cause of PIFP, in contrast to PTNP patients and healthy volunteers, have a central processing disorder of trigeminal pain stimuli at the brainstem level, which fundamentally distinguishes them from the other two groups and explains the persistent pain. We will directly compare brainstem network characteristics using fMRI including up- and downstream information patterns and will use partial correlation and dynamic causal modelling to characterize these patterns in healthy controls and these two facial pain types (PIFP & PTNP). Our primary outcome is the difference between PTNP and PIFP patients and healthy controls in brainstem functional neuroimaging using a standardized trigemino-nociceptive protocol. Secondary outcomes are distinguishing patients before and after a nerve block (only in PIFP patients) in brainstem imaging and differences between PIFP patients with subtle changes in CIBD and/or intraoral QST and PIFP patients without and PTNP patients and healthy controls.

• DFG Programme: Research Grants