Transient Receptor Potential (TRP) Ion Channels in Orofacial Pain

Orofacial pain, including temporomandibular joint disorders pain, trigeminal neuralgia, dental pain, and debilitating headaches, affects millions of Americans each year with significant population health impact. Despite the existence of a large body of information on the subject, the molecular underpinnings of orofacial pain remain elusive. Two decades of research has identified that transient receptor potential (TRP) ion channels play a crucial role in pathological pain. A number of TRP ion channels are clearly expressed in the trigeminal sensory system and have critical functions in the transduction and pathogenesis of orofacial pain. Although there are many similarities, the orofacial sensory system shows some distinct peripheral and central pain processing and different sensitivities from the spinal sensory system. Relative to the extensive review on TRPs in spinally-mediated pain, the summary of TRPs in trigeminally-mediated pain has not been well-documented. This review focuses on the current experimental evidence involving TRP ion channels, particularly TRPV1, TRPA1, TRPV4, and TRPM8 in orofacial pain, and discusses their possible cellular and molecular mechanisms.