Most practitioners have historically considered chronic pain to be largely from peripheral nociceptive input (i.e. damage or inflammation). If they consider central nervous system involvement in pain, they typically focus entirely on psychological factors. We now understand that non-psychological central nervous system factors can markedly increase (sensitization) or decrease pain sensitivity, in that the CNS is now thought of as “setting the volume control” or gain on pain processing and determining what nociception is felt as pain. The most highly prevalent pain conditions in younger individuals are now thought to be more “central” than “peripheral,” and centralized pain or central sensitization can also be identified in subsets of individuals with any nociceptive or neuropathic pain state. This is not currently appreciated in clinical practice so there is marked overuse of treatments for acute/nociceptive pain (opioids, injections, surgery) for treating centralized pain, and underuse of non-opioid centrally-acting analgesics and non-pharmacological therapies.