Companies seeking to evaluate new analgesic entities face two critical early choices: which pain model to utilize and which research site(s) with which to partner. The vast array of pain models and sites available to sponsors can be daunting, and a mistaken choice in early development can lead to poor-quality data and ultimate project failure. This can be particularly devastating for start-ups or small sponsors with limited funding but also affects sponsors and contract research organizations (CROs) of any size. Combining the appropriate pain model with the most effective research site can prevent false negative results from forcing abandonment of a good product or false positive results from leading to costly failure down the line.