Chulalongkorn University Dental Journal

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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.



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