Interaction of IL-1β and P2X3 receptor in pathologic masseter muscle pain

The exact mechanism underlying chronic masseter muscle pain, a conspicuous symptom in temporomandibular disorder, remains unclear. We investigated whether expression of P2X₃ receptor (P2X₃R) is involved in mechanical hyperalgesia after contraction of masseter muscle (CMM). As compared with sham rats, the head-withdrawal threshold (HWT) to mechanical pressure stimulation of masseter muscle (MM) (but not after similar stimulation of facial skin) was significantly lower, and IL-1β level was significantly higher, in CMM rats on day 7 after CMM. The mean percentage of FG-labeled P2X ₃R-positive neurons was significantly increased in TG following successive IL-1β injections into the MM for 7 days. Successive administration of an IL-1β receptor-antagonist into the MM attenuated the increase of P2X₃-IR cells in the TG. ATP release from MM after 300-g pressure stimulation of MM was also significantly enhanced after CMM. Administration into MM of the selective P2X_3,2/3 receptor antagonist A-317491 attenuated the decrement of HWT in CMM rats. A significant increase in HWT was also observed at 30 min after A-317491 (60 μg) injection in IL-1β-injected rats. These findings suggest that P2X₃R expression associated with enhanced IL-1β expression and ATP release in MM has a possible important role in MM mechanical hyperalgesia after excessive muscular contraction.