Persistent pain can be caused by injury to a nerve and happen in the moment of that injury. It is not related to the length of time it has been present, for example, six months or a year. It relates the pathological process that causes it. Here we see a lumbar disc herniating into a nerve root. In that instant the pain transforms from acute pain to persistent pain. This is marked by injury to the nerve root, made up of tens of thousands of nerve cell axons. These release massive amounts of Substance-P into the spinal cord where these nerve roots enter the central nervous system. The pain signal spreads out to a greater area, activates specialized receptors (NMDAR) and causes the pain signal to become greater in strength and persistent firing (Long-Term Potentiation). This is known as wind-up. The wound-up signal crosses to the opposite side of the spinal cord and travels up to the brain, where it causes more Substance-P release and winds up at each of 16 regions of the brain. When it gets to the Amygdala, the signal is transformed into the perception of pain. The signal fires on its own with or without further stimulus from the area of injury. The brain's normal analgesic mechanisms are overwhelmed and attempts to stop this signal fail.
