Purinergic Signaling and Dental Orofacial Pain

Abstract

Pain is a common complaint of patients in the dental clinic. Patient with dental orofacial pain usually presents with hyperalgesia and allodynia. Its management has been a challenge, especially in the status of chronic pain or neuropathic pain. Purinergic signaling is dictated by ATP release, purinergic receptors activation, and sequential hydrolysis of ATP. Purinergic signaling participates in nociception processing in the sensory nerves by control of pain signal transduction, modulation, and sensitization. Since purinergic receptors are preferentially expressed in trigeminal nerves, purinergic singling may play a crucial role in the development of dental orofacial pain. In this chapter, we overview the expressions of purinergic receptors as well as the machinery for ATP release, ATP degradations, and adenosine generation in trigeminal nerves. Specifically, the roles of ATP signaling in dental orofacial pain generation and central sensitization via activation of P2 receptors and adenosine signaling in analgesia via activation of P1 receptors in trigeminal nerves are updated. We also discuss the affection of ecto-nucleotidases, the major enzymes responsible for extracellular ATP degradation and adenosine generation in trigeminal nerves that drive the shift from ATP-induced pain to adenosine-induced analgesia. This chapter provides advanced outlines for purinergic signaling in trigeminal nerves and unveils potential therapeutic targets for the management of dental orofacial pain.