Acute pulpitis is characterized by severe spontaneous pain and a marked pain response to hot and cold stimuli, and patients have difficulty sleeping because of pain (Wolters et al., 2017). Symptomatic pulpitis can lead to intense temperature-related pain, and spontaneous toothache and is one of the main reasons that patients seek dental treatment (McCarthy et al., 2010). A total of 74.5 % of acute pulpitis patients experience lingering severe spontaneous pain and provoked pain (Hashemipour & Borna, 2014). Therefore, an in-depth understanding of the causes and potential mechanisms of acute pulpitis pain is of great significance for identifying strategies to relieve acute pulpitis pain, but the these causes and mechanisms have not yet been fully elucidated.

Sensation in the oral area is mainly produced by nerve fibers surrounded by the trigeminal ganglia, which include the cell bodies of primary afferent nerve cells in dental pulp (Hossain et al., 2019). The trigeminal ganglia are involved in pain caused by dental injury, and most neuroinflammation and hyperalgesia can be observed in other inflammatory tissues (Byers & Närhi, 1999). Touch and pain, which are produced by a cellular phenomenon called mechanical conduction, are very important for perceiving the external environment. During this phenomenon, temperature and chemical stimuli are converted into electrical signals through molecular transducers called mechanical ion channels, which specialize in detecting mechanical stimuli (Reza, 2020). In recent decades, multiple ion channels in dental primary afferent (DPA) neurons and odontoblasts have been found to participate in tooth pain conduction. TRP ion channels have been found to be related to toothache transmission in pulpitis. TRPV1 mRNA and protein are expressed at high levels in the trigeminal ganglia and on odontoblasts in the tooth pulp (Kim et al., 2011, Tsumura et al., 2012). Inflammatory mediators can decrease the activation threshold of TRPV1, which can regulate the intracellular Ca2+ concentration and thus play an important role in temperature signals or tooth pain (Jardin et al., 2017; Lee et al., 2019). TRPA1 and TRPV1 are expressed at similar levels in sensory neurons (Usoskin et al., 2015). In addition, TRPA1 is involved in tooth pain transmission which occurs via a similar signaling pathway to TRPV1 channels (Ca2+, ATP, PANX-1, P2Y, P2X3 purinoceptors) (Shibukawa et al., 2015). TRPC5 transmits cold signals in healthy teeth and underlies prolonged cold sensation and pain (Bernal et al., 2021). TRPC5 underlies prolonged cold sensing via its relative sensitivity to intracellular Ca2+ and lack of desensitization (Blair et al., 2009). TACAN (Tmem120a) is a newly identified potential mechanical ion channel protein on the cell membrane. For a candidate channel to be considered intrinsically mechanosensitive, it should meet eight criteria, including being expressed in mechanically sensitive cells (P & P, 2007). TACAN meets at least seven of these eight conditions, and reduced TACAN expression leads to a reduction in the mechanical-induced current of the injured receptor (Lou et al., 2020).

Tissue expression analysis showed that TACAN is highly expressed in the heart, kidney, colon nerve and dorsal root nerve in mice (Lou et al., 2020). A study also found that the TACAN ion channel is permeable to Ca2+. Another study showed that TACAN is expressed in the dorsal root ganglion in rats and plays a role in mechanical pain induced by inflammatory mediators. Downregulation of TACAN expression in the dorsal root ganglion reduces the pain response to inflammatory mediators in rats (J.M. et al., 2020). We speculate that TACAN may be similar to TRPV1, acting as a mechanical ion channel that produces acute pulpitis-related pain. However, it is still unclear whether TACAN is expressed in the trigeminal nerve and whether pain is transmitted in acute pulpitis via regulation of TACAN expression in the trigeminal ganglia. Here, we aimed to elucidate the role of TACAN in rat model of acute pulpitis pain.