Highlights
- •Pain-related phenotypes (PP; analgesic requirements or pain scores) were examined.
- •The rs3845446 single nucleotide polymorphism (SNP) was genotyped in the subjects.
- •The G allele of the rs3845446 SNP enhanced PP after gastrointestinal surgery (GS).
- •Association of the SNP with PP after GS opposed to that after orthognathic surgery.
- •Cav2.3 channel functions might differentiate PP after GS and orthognathic surgery.
Abstract
Cav2.3 (R-type) voltage-activated Ca2+ 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.
Key words
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Article info
Publication history
Published online: July 29, 2016
Accepted:
July 6,
2016
Received in revised form:
June 22,
2016
Received:
February 14,
2016
Footnotes
Kojiro Amano and Daisuke Nishizawa contributed equally to this work.
This work was supported by grants from MEXT KAKENHI (20602020, 20390162, 23390377, 26293347, 26860360, and S-001), the Ministry of Health, Labour and Welfare of Japan (H21-3jigan-ippan-011, H22-Iyaku-015, and H25-Iyaku-020), Grants-in-Aid for the U.S.-Japan Cooperative Medical Science Program, National Cancer Center Research and Development Fund, Smoking Research Foundation, and Astellas Foundation for Research on Metabolic Disorders.
Kazutaka Ikeda received support from Eisai Co, Ltd, Taisho Pharmaceutical Co, Ltd, Nobelpharma Co, Ltd, and Kurabo Industries, Ltd, for projects unrelated to this research and speaker's fees from Taisho Pharmaceutical Co, Ltd, and Japan Tobacco, Inc. The authors have no conflicts of interest to declare.
Identification
Copyright
© 2016 by the American Pain Society
