Opioid analgesics are the most widely used drugs to treat moderate to severe pain, yet in addition to profound analgesia, these agents also produce significant side-effects consisting of miosis, sedation, nausea and vomiting, cognitive impairment, constipation, rapid-onset hypotension and on occasion life-threatening respiratory depression (1–4). There is considerable inter-individual variability in the clinical response to opioid analgesics (5,6). For example, the minimal effective analgesic concentration for opioids, such as morphine, pethidine, alfentanil and sufentanil, varies among patients by factors of 5–10 (7–9). Furthermore, despite the fact that most clinically used opioids are selective for μ-opioid receptors (OPRM1), as defined by their selectivity in receptor-binding assays, patients may respond far better to one μ-opioid than another, both with respect to analgesic responsiveness and side-effects (10–12). As such, there is a substantial need to understand biological and genetic basis for inter-individual variability and develop new biological markers that will provide valid and reliable predictions of individual responses to opioid therapy.
