Ninagawa Jun, Sumitani Masahiko, Nishizawa Daisuke, Nagashima Makoto, Mietani Kazuhito, Abe Hiroaki, Inoue Reo, Hozumi Jun, Tsuchida Rikuhei, Ikeda Kazutaka, Yamada Yoshitsugu
Department of Anesthesiology and Pain Relief Center, The University of Tokyo Hospital.
Department of Anesthesiology, National Center for Child Health and Development.
Medicine (Baltimore). 2020 Jan;99(5):e18924. doi: 10.1097/MD.0000000000018924.
Adiponectin is an adipose tissue-derived cytokine that exerts its antiinflammatory effects by binding to 2 adiponectin receptors, adiponectin receptor 1 (ADIPOR1) and adiponectin receptor 2 (ADIPOR2). However, the role of these adiponectin receptors on inflammatory pain remains unclear. We investigated the association between single nucleotide polymorphisms (SNPs) of these genes and inflammatory pain, such as postoperative pain and cancer pain.We analyzed 17 SNPs of the ADIPOR1 gene and 27 SNPs of the ADIPOR2 gene in 56 adult patients with postlaparotomy pain. We compared these genotypes with pain intensity and opioid consumption, adjusting for multiple testing. We analyzed the genotypes of 88 patients with cancer pain and examined the association of the relevant SNP(s) with pain intensity and opioid consumption.One variant of the ADIPOR1 gene (rs12045862) showed significant association with postoperative pain intensity; patients with minor allele homozygote (n = 7) demonstrated significantly worse pain intensity than that of combined patient group exhibiting major allele homozygote or the heterozygote (n = 49; Mann-Whitney test, P < .00002), although their opioid consumptions were comparable. Cancer pain intensity between minor allele homozygote patients (n = 7) and other 2 genotype patients (n = 81) were comparable.The rs12045862 SNP of the ADIPOR1 gene was associated with postoperative pain but not cancer pain. This might result from functional alteration of the ADIPOR1 signalling pathways, which influence the inflammatory process. ADIPOR1 may be a novel potential target for developing analgesics of postoperative pain.
脂联素是一种源自脂肪组织的细胞因子,它通过与两种脂联素受体,即脂联素受体1(ADIPOR1)和脂联素受体2(ADIPOR2)结合来发挥其抗炎作用。然而,这些脂联素受体在炎性疼痛中的作用仍不清楚。我们研究了这些基因的单核苷酸多态性(SNP)与炎性疼痛(如术后疼痛和癌痛)之间的关联。我们分析了56例成年剖腹术后疼痛患者中ADIPOR1基因的17个SNP和ADIPOR2基因的27个SNP。我们将这些基因型与疼痛强度和阿片类药物消耗量进行比较,并对多重检验进行了校正。我们分析了88例癌痛患者的基因型,并检查了相关SNP与疼痛强度和阿片类药物消耗量的关联。ADIPOR1基因的一个变体(rs12045862)与术后疼痛强度显著相关;次要等位基因纯合子患者(n = 7)的疼痛强度明显比主要等位基因纯合子或杂合子的联合患者组(n = 49;Mann-Whitney检验,P <.00002)更差,尽管他们的阿片类药物消耗量相当。次要等位基因纯合子患者(n = 7)和其他两种基因型患者(n = 81)之间的癌痛强度相当。ADIPOR1基因的rs12045862 SNP与术后疼痛相关,但与癌痛无关。这可能是由于ADIPOR1信号通路的功能改变,其影响了炎症过程。ADIPOR1可能是开发术后疼痛镇痛药的一个新的潜在靶点。