The common causes of leg pain without effect of various painkillers are fracture, malignant tumor, lumbar disc herniation, etc. The painkillers have no direct therapeutic effect on fracture. 1. Fracture: there is a clear history of trauma, due to the fracture of the broken end of the fracture stimulation of the surrounding tissues caused by pain, painkillers do not have a direct therapeutic effect on the fracture, so the effect is not obvious. 2. Lumbar intervertebral disc herniation: if the disc herniation is more serious, the nerve root is obviously compressed, at this time the effect of painkillers is worse, and it is necessary to release the nerve root compression to reduce the pain. 3. Malignant tumors: due to the erosion of tumor cells in the surrounding tissues, causing bone destruction, inflammatory response, etc., the pain is more intense, at this time the painkillers are less effective. Causes of leg pain are more reasons, may also be blood clots, diabetes complications, lumbar spinal stenosis, etc., it is recommended to consult a doctor in time, after the cause of the disease is clear, targeted treatment.