Association between the rs7583431 single nucleotide polymorphism close to the activating transcription factor 2 gene and the analgesic effect of fentanyl in the cold pain test

Aoki, Yosuke; Nishizawa, Daisuke; Yoshida, Kaori; Hasegawa, Junko; Kasai, Shinya; Takahashi, Kaori; Koukita, Yoshihiko; Ichinohe, Tatsuya; Hayashida, Masakazu; Fukuda, Ken‐ichi; Ikeda, Kazutaka

doi:10.1002/npr2.12012

Cited by 5 publications

(3 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As mentioned above, we conducted GWASs of phenotypes that are related to opioid sensitivity and candidate gene studies [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. Several candidate SNPs were found to be associated with phenotypes that are related to opioid sensitivity/pain.…”

Section: Discussionmentioning

confidence: 99%

“…We also conducted GWASs of phenotypes that are related to opioid sensitivity and candidate gene studies [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. In our GWASs, although genetic variants that were significantly associated with opioid responsiveness for the treatment were not found in patients with chronic pain [30], we identified several SNPs, including the rs2952768 SNP (located near the METTL21A [FAM119A] and CREB1 gene regions), that were significantly associated with postoperative opioid analgesic requirements in subjects who underwent cosmetic orthognathic surgery for mandibular prognathism [18].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Genome-Wide Association Study Identifies Genetic Polymorphisms Associated with Estimated Minimum Effective Concentration of Fentanyl in Patients Undergoing Laparoscopic-Assisted Colectomy

Nishizawa

Mieda

Tsujita

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

Sensitivity to opioids varies widely among individuals. To identify potential candidate single-nucleotide polymorphisms (SNPs) that may significantly contribute to individual differences in the minimum effective concentration (MEC) of an opioid, fentanyl, we conducted a three-stage genome-wide association study (GWAS) using whole-genome genotyping arrays in 350 patients who underwent laparoscopic-assisted colectomy. To estimate the MEC of fentanyl, plasma and effect-site concentrations of fentanyl over the 24 h postoperative period were estimated with a pharmacokinetic simulation model based on initial bolus doses and subsequent patient-controlled analgesia doses of fentanyl. Plasma and effect-site MECs of fentanyl were indicated by fentanyl concentrations, estimated immediately before each patient-controlled analgesia dose. The GWAS revealed that an intergenic SNP, rs966775, that mapped to 5p13 had significant associations with the plasma MEC averaged over the 6 h postoperative period and the effect-site MEC averaged over the 12 h postoperative period. The minor G allele of rs966775 was associated with increases in these MECs of fentanyl. The nearest protein-coding gene around this SNP was DRD1, encoding the dopamine D1 receptor. In the gene-based analysis, the association was significant for the SERP2 gene in the dominant model. Our findings provide valuable information for personalized pain treatment after laparoscopic-assisted colectomy.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genome-Wide Association Study Identifies Genetic Polymorphisms Associated with Estimated Minimum Effective Concentration of Fentanyl in Patients Undergoing Laparoscopic-Assisted Colectomy

Nishizawa

Mieda

Tsujita

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…Transcriptionally activated ATF2 regulates various genes that regulate cellular responses associated with pain and inflammatory responses. 25 Activation of p38-MAPK and ATF2 is important in central NP sensitization and spinal nerve ligation in chronic pain models has been shown to induce mechanical nociceptive hyperalgesia and thermal nociceptive hypersensitivity in rats, leading to increased expression of ATF2 and ATF3 in the ipsilateral dorsal root ganglia and spinal cord. Intrathecal injection of ATF siRNA reverses nociceptive hypersensitivity.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of the Spinal Dorsal Horn in Mice with Neuropathic Pain After Exercise

Bai¹,

Zhang²,

Zhou³

et al. 2023

JPR

View full text Add to dashboard Cite

Purpose Neuropathic pain (NP) is a chronic pain state with a complex etiology that currently lacks effective treatment in clinical practice. Studies have found that exercise training can alleviate NP hyperalgesia, but the specific mechanism remains unclear. Here, we sought to identify proteins and signaling pathways critical for mediating the effects of treadmill training on NP in a mouse model of spared nerve injury (SNI). Methods We used Tandem Mass Tag (TMT) technology for proteins and signaling pathways identification. Functional enrichment analyses were conducted using DAVID and Metascape software. Ingenuity pathway analysis was used to conduct functional annotation and analyze alterations in canonical pathways and molecular networks. Reverse transcription quantitative PCR (RT-qPCR) was used to confirm the results of proteomics analysis. Results A total of 270 differentially expressed proteins were screened in the detrained and trained groups ( P ≤0.05). Enrichment and ingenuity pathway analysis revealed the effects of treadmill training on autophagy, cAMP-mediated signaling, calcium signaling and NP signaling in dorsal horn nerves. Treadmill training reduced the expression of Akt3, Atf2, Gsk3b, Pik3c3, Ppp2ca , and Sqstm1 , and increased the expression of Pik3cb in the autophagic pathway. Conclusion Our results suggest that treadmill training may alleviate nociceptive hyperalgesia in NP mice by modulating the autophagic pathway, providing unique mechanistic insights into the analgesic effects of exercise.

show abstract