Chronic pain and the opioid epidemic need early, upstream interventions to aim at meaningful downstream behavioral changes. A recent pain neuroscience education (PNE) program was developed and tested for middle-school students to increase pain knowledge and promote healthier beliefs regarding pain. In this study, 668 seventh-grade middle-school students either received a PNE lecture (n = 220); usual curriculum school pain education (UC) (n = 198) or PNE followed by two booster (PNEBoost) sessions (n = 250). Prior to, immediately after and at six-month follow-up, pain knowledge and fear of physical activity was measured. Six months after the initial intervention school, physical education, recess and sports attendance/participation as well as healthcare choices for pain (doctor visits, rehabilitation visits and pain medication use) were measured. Students receiving PNEBoost used 30.6% less pain medication in the last 6 months compared to UC (p = 0.024). PNEBoost was superior to PNE for rehabilitation visits in students experiencing pain (p = 0.01) and UC for attending school in students who have experienced pain > 3 months (p = 0.004). In conclusion, PNEBoost yielded more positive behavioral results in middle school children at six-month follow-up than PNE and UC, including significant reduction in pain medication use.