Apical periodontitis-induced mechanical allodynia: A mouse model to study infection-induced chronic pain conditions

Abstract

Infection-induced chronic pain is an under-studied pain condition. One example is apical periodontitis, which evokes considerable mechanical allodynia that persists after treatment in 7% to 12% of patients. Available analgesics often provide incomplete relief. However, a preclinical model to study pain mechanisms associated with apical periodontitis is not available. Here, we report a mouse model of apical periodontitis to facilitate studies determining mechanisms mediating persistent infection-induced pain. Mice were anesthetized and the left first molar was exposed to the oral environment for six weeks. Bone resorption, as an indicator of apical periodontitis, was quantified using microcomputed tomography. Mechanical allodynia was determined using extraoral von-Frey filaments in both male and female mice. The expression of c-fos in the medullary dorsal horn was assessed using immunohistochemistry. Mice with apical periodontitis developed significant mechanical allodynia by day 7 that was maintained for 42 days. Mechanical thresholds were significantly lower in females compared to males. Administration of ibuprofen, morphine, or MK-801 reversed mechanical allodynia. Finally, apical periodontitis triggered an upregulation of c-fos in the medullary dorsal horn. Collectively, this model simulates signs of clinical pain experienced by patients with apical periodontitis, detects sex differences in allodynia, and permits the study of peripheral and central trigeminal pain mechanisms.