An interesting observation made in this study is that the minor CACNA2D2 G>A SNP was not found in any of the 16 high responders to remifentanil. This gene encodes a member of the alpha-2/delta subunit family, a protein in the voltage-dependent calcium channel complex. All the high responders to the opioid remifentanil had the major allele of CACNA2D2, suggesting an association between this allele and high opioid sensitivity. Interestingly, genetic variations of the Na+, K+, and Ca2+−channel genes have also been associated with migraine and neuropathic pain [59]. Very few, if any, study on opioid sensitivity in relation to the gene encoding the calcium channel fragment, CACNA2D2 allele, has so far been reported. Interestingly, a recent study demonstrated an association between the voltage-gated calcium channels and the A118G OPRM1 polymorphism [60].
