Breakthrough pain is pain that occurs despite the use of regular analgesic medication. It occurs following dips in plasma concentration with immediate release analgesics. It is less common with slow release preparations but can still occur towards the end of a dosage interval. Frequent episodes of breakthrough pain indicate that the background level of analgesia is insufficient and a higher dose is required. Rapid acting analgesics can be prescribed in addition to their regular analgesia.

The slow therapeutic response to transdermal fentanyl renders it unsuitable for the relief of breakthrough pain but the constant plasma drug level reduces the risk of breakthrough pain occurring. The most commonly prescribed rapid acting opiate for breakthrough pain is immediate release morphine. Alternatives include fentanyl lozenges or buccal preparations although these are more expensive and are consequently less commonly prescribed. The principle involved in calculating morphine doses for breakthrough pain is to convert the daily opioid dose to an equivalent daily morphine dose and use one sixth of this dose when required in addition to the background opioid therapy.⁷ Patients requiring more than two doses of analgesia per day for breakthrough pain should have their analgesic medication reviewed.

Some patients also suffer from "incident pain" which is similar to breakthrough pain but is associated with specific events such as dressing changes, being moved or other medical procedures. In these situations patients will be prescribed rapid acting analgesics for use immediately prior to and during the procedures.