Project Grant K99DE036046

The National Institute of Dental and Craniofacial Research awarded the Regents of the University of Michigan $135,000 on August 1, 2026, under the Oral Diseases and Disorders Research program (CFDA 93.121) to support research dissecting the neural and molecular mechanisms of trigeminal low-temperature sensation.

The funded research addresses orofacial neuropathic pain stemming from somatosensory nervous system dysregulation, including cold allodynia and cold hyperalgesia in conditions such as chemotherapy-induced neuropathy and trigeminal neuralgia. Current treatments fail to alleviate these cold-sensation symptoms because the underlying cellular and molecular mechanisms for low-temperature sensation remain poorly defined. The investigator will employ intersectional genetic strategies in mice, combining thermoelectric cooling probes, in vivo trigeminal functional imaging, multiplexed in situ hybridization, neural tracing, and artificial intelligence-based behavioral analyses to delineate the neural and molecular logic underlying low-temperature sensation. Preliminary data reveal that CHRNA7+ trigeminal A-delta nociceptors encode noxious cold sensation in teeth independently of the canonical cool receptor TRPM8, providing evidence that low-temperature encoding is distributed across multiple trigeminal classes. The work will define molecular and neural mechanisms underlying orofacial low-temperature sensation and characterize behavioral outputs and central projections of low-temperature-encoding trigeminal populations using optogenetics and machine learning.

Performance occurs at the University of Michigan, Ann Arbor, Michigan, with a period of performance from August 1, 2026, through July 31, 2028. The award is classified as a project grant.