There are some adverse reactions reported by patients. These don't happen very often and aren't severe. Some patients report increased pain and stiffness. Others have headaches, leg pain, nausea, and diarrhea.

Symptoms don't last long and are all gone within one week. There can be long-term problems if a nerve is damaged. Nerve pain, changes in sensation, and leg weakness can occur. Otherwise, prolotherapy is considered a fairly "benign" treatment. In other words, it may or may not help.

Some studies show certain patients are less likely to benefit. These include patients who use tobacco products, alcohol, and illegal drugs. Patients with fibromyalgia or a previous history of back surgery are less likely to be helped by prolotherapy.