Hypothetical model of SCD pain. Red dashed lines represent acute pain episodes worsening in severity and duration over the lifespan. Blue line represents the required opioid dose to achieve analgesia, which becomes harder and harder to achieve as chronic pain and NP develop over time. Chronic pain can be a result of acute pain episodes and their cumulative damage as well as a cause, because exacerbations of chronic pain/NP may be a trigger for acute pain. Because current assessment tools cannot definitively isolate the contributions of inflammatory pain, nociceptive pain, and NP to overall chronic pain, we suggest formally evaluating for NP when chronic pain shows clear worsening, as well as when pain seems to become refractory to escalating doses of opioid.