The A118G single nucleotide polymorphism has been reported to be associated with elevating27 or decreasing11,31 the pain threshold of the 118G allele carriers. Healthy volunteers carrying the variant allele, for example, have been shown to have higher pain (i.e. pressure) threshold when compared to homozygous 118A subjects27. On the other hand, it has been reported that the morphine requirement for post cesarean analgesia and pain scores in patients homozygous for the 118A allele were significantly lower than carriers of the 118G allele (either 118AG or 118GG)11. This conflicting effect of the polymorphism on pain threshold may be a result of an endogenous opioid that exerts opposite effects on the variant receptors (i.e. higher receptor affinity) than that observed with morphine. For instance, a recent study in healthy volunteers found that carriers of the 118G allele displayed an enhanced cortisol response to naloxone but a dampened response to psychosocial stress compared to 118A carriers32. The authors suggested that with a higher MOR affinity, 118G allele carriers have a greater inhibitory opioidergic tone on corticotropin releasing hormone neurons in the arcuate nucleus.
