In Neural Prolotherapy, the subcutaneous (under the skin) nerves are recognised as a source of pathology. These nerves in a pathologic state can cause neurogenic inflammation and pain. The pain is often burning, sharp and the areas of pain are very tender. Common nerves to cause this are the cluneal nerves over the buttocks, an often overlooked cause of low back pain.

Ligaments, tendons and joints have special C pain fibre innervation. When these C fibres are irritated anywhere along their length they transmit impulses in both forward and reverse directions. The forward direction of the nerve signal causes pain perception as the signal travels up to the brain. It also has a local reflex action out to the muscles, causing a reflex muscle spasm. The reverse signal goes down the nerve where substance P is released causing swelling and pain. The swollen painful nerves become self-perpetuating, especially when compressed, for example when lying on the hips at night. Dr John Lyftogt in New Zealand has discovered that 5% glucose relieves this pain and if applied a few times the pain, when it recurs, is less each time, and can eventually go away altogether.