Acid‐sensing ion channels in trigeminal ganglion neurons innervating the orofacial region contribute to orofacial inflammatory pain

Abstract

Summary Orofacial pain is a common clinical symptom that is accompanied by tooth pain, migraine and gingivitis. Accumulating evidence suggests that acid‐sensing ion channels ( ASIC s), especially ASIC 3, can profoundly affect the physiological properties of nociception in peripheral sensory neurons. The aim of this study is to examine the contribution of ASIC s in trigeminal ganglion ( TG ) neurons to orofacial inflammatory pain. A Western blot ( WB ), immunofluorescence assay of labelled trigeminal ganglion neurons, orofacial formalin test, cell preparation and electrophysiological experiments are performed. This study demonstrated that ASIC 1, ASIC 2a and ASIC 3 are highly expressed in TG neurons innervating the orofacial region of rats. The amplitude of ASIC currents in these neurons increased 119.72% (for ASIC 1‐like current) and 230.59% (for ASIC 3‐like current) in the formalin‐induced orofacial inflammatory pain model. In addition, WB and immunofluorescence assay demonstrated a significantly augmented expression of ASIC s in orofacial TG neurons during orofacial inflammation compared with the control group. The relative protein density of ASIC 1, ASIC 2a and ASIC 3 also increased 58.82 ± 8.92%, 45.30 ± 11.42% and 55.32 ± 14.71%, respectively, compared with the control group. Furthermore, pharmacological blockade of ASIC s and genetic deletion of ASIC 1 attenuated the inflammation response. These findings indicate that peripheral inflammation can induce the upregulation of ASIC s in TG neurons, causing orofacial inflammatory pain. Additionally, the specific inhibitor of ASIC s may have a significant analgesic effect on orofacial inflammatory pain.