There have been a series of studies in both healthy volunteers and in clinical patients suggesting that, the A118G variant may alter response to opioid drugs (see [1] for review). Lotsch and colleagues reported the 118G allele conferred smaller analgesic effects and produced less pupillary constriction during morphine and morphine-6-glucuronide (MG6) infusion [13-15]. In an experiment using a measure of pain tolerance to electrical stimulation, higher MG6 concentrations were associated with a 25% increase in current (C25) participants with the 118G allele [16,17]. Similar findings have been found for alfentanil [18] and levomethdone [19]. In clinical studies, data from patients with the 118G polymorphism tend to confirm data from experimental pain studies where those patients with the variant required higher alfentanil doses for analgesia or more morphine during colorectal surgery [20] or for pain/toxicity associated with morphine use in renal failure [13,14]. However, it appears that the effects may be drug or disease specific owing to presumed variation in environmental and/or other uncontrolled variables [1,21,22].
