Buprenorphine is a partial agonist at μ-receptor. The data in Table 1 suggests that the affinity of buprenorphine for ORL1 receptor is approximately 50 times lower than for μ-receptor and many preclinical reports indicate that ORL1 agonism may contribute to reducing its antinociception (pain killing) effect at high concentration.
In addition, a number of studies suggest that buprenorphine dose needs for treatment of pain are much lower compared to doses used for the treatment of opioid addiction.
The typical analgesic dose of buprenorphine is 0.3–0.6 mg (im or iv)[around 1.5mg SL], and its analgesic effects last approximately 6 hours for iv. A review of clinical trials showed that buprenorphine was effective in 25/26 trials. Contrary to previous concerns, no analgesic ceiling effect and no antagonism on a combination of buprenorphine with pure μ-OR agonists is seen within the therapeutic dose range in humans.12,28
Some authors believe that false myths about buprenorphine based on unconfirmed animal data and early clinical research came into textbooks on pharmacology and pain approximately 30 years ago and have been difficult to eradicate.28 The fact is that in clinical practice there is no bell-shaped dose–response curve, there is no plateau on the dose–response curve, and there is no antagonist effect from buprenorphine on other μ-opioid agonists. This was also the conclusion by a panel of world experts convened to review pharmacology of buprenorphine and available evidence.
Although buprenorphine has demonstrated very high affinity for μ-receptors, it occupies fewer receptors for analgesia, which leads to a significant receptor reserve for other μ-agonists. Buprenorphine increases μ-receptor expression, which allows other μ-agonists to interact with receptors.
Supplemental dosing with an opioid is the main treatment suggested to manage breakthrough pain in cancer patients.