Objective Studies have shown it is possible to elicit a tension-type headache episode in 15 to 30% of healthy individuals following a tooth-clenching or stress-inducing task. Despite this, no studies have attempted to understand why some healthy individuals develop a headache episode while others do not. Methods The present randomized, single-blind, controlled study recruited 60 healthy participants who participated in a 30-minute tooth-clenching task and 10 participants who participated in a control task. Before the tasks, participants had their pericranial tenderness and pain modulation profiles (wind-up ratio and conditioned pain modulation) assessed. Two hours later, pericranial tenderness and pressure pain thresholds were assessed as well as any developing temporomandibular disorders. Pain diaries were kept for 24 hours to register any developing pain or headache. Results Participants with a decrease in pericranial tenderness after the tooth-clenching task were less likely to develop headache when compared to participants without. Pain modulation profiles could not predict who developed headache and who did not. Finally, no difference was found between groups for developing temporomandibular disorders. No difference in frequency of participants who developed headache was found between the tooth-clenching and the control task. Conclusions In conclusion, it was shown that increased pericranial tenderness was not required to trigger an episode of tension-type headache in healthy participants. Furthermore, pain modulation profiles could not predict who developed headache and who did not. Finally, activation of descending inhibitory pathways, as assessed by decreases in pericranial tenderness, was protective against the development of headache. These findings provide new insights into the pathophysiology of experimentally-induced tension-type headache.