Title : Astrotactin 2 as novel analgesic target candidate for cancer pain and opioid sparing: An exploratory genetic polymorphism analysis
Abstract:
Introduction: Cancer pain impairs not only physical functions but also social functions and roles. Neuronal protein astrotactin 2 (ASTN2) fulfills a function to regulate the release of neuronal adhesions to the glial fiber. Genetic variability in the ASTN2 gene was reportedly associated with opioid requirements during the postsurgical periods.
Method: A total of 72 cancer pain patients rated their pain on an 11?point numerical rating scale twice before and after increasing opioid analgesics. Three single nucleotide polymorphisms (SNPs) of the ASTN2 gene were investigated whether these are associated with cancer pain intensity, opioid requirements (intravenous fentanyl-equivalent doses) based on weight, and analgesic responsiveness to increased opioid analgesics. We analyzed associations among genotypes, and these phenotypes using the Kruskal-Wallis test and the post-hoc test if necessary.
Result: Among the three SNPs of the ASTN2 gene, two SNPs (rs958804 and rs7858836), reported in the previous study with postoperative pain, did not demonstrate any associations with cancer pain intensity and opioid requirements. Minor allele homozygosity (n=2) of one SNP (rs10491577) was linked to more opioid requirements (p=0.018) and lower opioid responsiveness (p=0.003) than major alle homozygosity (n=54) and heterogeneity (n=16) when controlling cancer pain intensity at the comparative level among three genotypes.
Discussion: Our result preliminarily suggests that the SNP of the ASTN2 gene might be potential candidate loci for responsiveness to opioid analgesics, and astrotactin 2 might be a possible target for developing a novel analgesics and the adjuvant pharmacotherapy with opioid sparing effect. Our results should be validated in a large?scale study with a larger sample size.
