Opposite Associations Between the rs3845446 Single-Nucleotide Polymorphism of the CACNA1E Gene and Postoperative Pain-Related Phenotypes in Gastrointestinal Surgery Versus Previously Reported Orthognathic Surgery

Cav2.3 (R-type) voltage-activated Ca(2+) channels (VACCs), encoded by the calcium channel, voltage-dependent, R-type, α1E subunit (CACNA1E) gene, are responsible for transmission of somatic inflammatory pain, and activation of antinociception elicited by visceral inflammatory pain stimuli. Carriers of the minor G allele of the rs3845446 single-nucleotide polymorphism (SNP) of the CACNA1E gene reportedly exhibit a decrease in opioid requirements to control typical somatic inflammatory pain after orthognathic surgery (ie, a painful cosmetic surgery), suggesting the downregulation of Cav2.3 VACC function that is responsible for transmission of somatic inflammatory pain in these carriers. Gastrointestinal surgery involves somatic and visceral inflammatory pain, in which visceral inflammatory pain stimuli activate Cav2.3 VACC-mediated antinociception. Unknown is whether pain-related phenotypes after gastrointestinal surgery are affected in these carriers. The present study used a correlational design to examine the effect of the rs3845446 SNP on postoperative pain-related phenotypes in 2 groups of patients who underwent gastrointestinal surgery. Carriers of the minor G allele had greater opioid requirements after laparoscopic colectomy when intravenous patient-controlled analgesia was used, and reported higher pain scores after open gastrointestinal surgery when postoperative analgesia was managed with continuous epidural analgesia and rescue analgesics. These results suggest that pain-related phenotypes after gastrointestinal surgery are enhanced in carriers of the minor G allele of the rs3845446 SNP, possibly through impairment of Cav2.3 VACC function that is responsible for the activation of visceral inflammatory pain stimulus-elicited antinociception.

Perspective: Carriers of the minor allele of the rs3845446 SNP of the CACNA1E gene required more opioid or reported higher pain scores after gastrointestinal surgery, and required less opioid after orthognathic surgery. The difference may result from the presence of visceral inflammatory pain stimulus that activates Cav2.3 VACCs-mediated antinociception.