• Weera Supronsinchai Ph.D.
• Robin James Storer Ph.D.

It is well known that pain in animal models is difficult to measure. c-Fos, the protein product
of the cellular immediate-early proto-oncogene gene, c-fos, can be activated in neuronal cells by
noxious sensory stimuli including chemical irritation, mechanical, thermal, and electrical stimulation.
The expression of c-Fos provides researchers with a tool by which the processing of somatosensory
information, particularly nociception, from the craniofacial regions can be better understood. c-Fos
is widely used as an indirect marker of neuronal activation after noxious stimulation in dental
pain research, including in the trigeminal nervous system as activated by craniofacial or orofacial
stimulation. Anatomical mapping of neurons activated by craniofacial stimulation can be used as a
tool to analyze the neural circuitry through which nociceptive information is transmitted, and as an
assay for the analgesic properties of various therapeutics. c-Fos expression can be correlated with
behavioral and electrophysiological studies and with the expression of other pain markers such as
calcitonin gene-related peptide or dynorphin. This narrative review intends as a primer on c-Fos and
focuses on research in which c-Fos has been used as a marker in animal models of dental and
craniofacial pain. We have sought to highlight recent advancement in the use of c-Fos as a marker of
pain among the multitude of studies currently published and discuss the strengths and limitations of
using this marker.

(CU Dent J. 2015;38:77-92)