Genetic risk factors for orofacial pain: Insights from animal models

Persistent orofacial pain states are complex heritable traits that, like other chronic pain states, require the coincident occurrence of two conditions or criteria. The first is an inciting event that causes an injury to an orofacial structure; inflammation of that structure then usually ensues. Many circumstances may cause such an injury, including trauma and surgery and even iatrogenic manipulation of a nerve during a dental treatment procedure. Other injuries result from malfunction of orofacial structures as a consequence of certain diseases, after a brain stroke, from the consumption of certain drugs, or after exposure to certain toxins. The common denominator of these events is activation of primary afferents innervating a part of the orofacial region or neurons in trigeminal nociceptive pathways in the central nervous system (CNS), as summarized in Chapters 16-18. The second criterion is the inheritance of certain genetic variants ("G") located within pain genes (or in the large intergenic spans of the genome), whose products interact with other genes ("GXG") and with nongenetic, environmental ("E") risk and protective factors ("GXE") to produce pathophysiological mechanisms that manifest in orofacial pain symptoms and their variation over time. These gene products may be expressed anywhere along the trigeminal somatosensory pathway (as well as in other sensory pathways that subserve the head and neck region).