From the Departments of Anesthesiology and Pain Relief Center.
Pain and Palliative Medicine, The University of Tokyo Hospital, Tokyo, Japan.
Anesth Analg. 2019 Mar;128(3):563-568. doi: 10.1213/ANE.0000000000003363.
Pro- and anti-inflammatory cytokines (adipokines) associated with adipose tissue can modulate inflammatory processes and lead to systemic inflammatory conditions such as metabolic syndrome. In the present pilot study, we investigated 3 major adipokines (leptin, adiponectin, and resistin) and 2 nonspecific proinflammatory cytokines (tumor necrosis factor α and interleukin-6) with regard to their association with postoperative pain intensity.
We analyzed a total of 45 single-nucleotide polymorphisms of the adipokines in 57 patients with postlaparotomy pain. We adjusted for multiple testing to reduce the chance of false-positive results by controlling the false discovery rate. Serum levels of the adipokines and proinflammatory cytokines were measured in another 36 patients undergoing laparotomy. A stepwise multiple linear regression analysis using these measurements and opioid dosages as independent variables was performed to explore the factors associated with postoperative pain.
Only 1 variant of the resistin gene (rs3745367) demonstrated a significant association with postoperative pain (P < .002). Patients exhibiting homozygosity for the minor alleles (n = 7; numerical rating scale [NRS], 2.3 ± 1.3) demonstrated lower pain intensity compared with those exhibiting homozygosity for the major alleles (n = 29; NRS, 3.8 ± 1.0; P = .004) and heterozygosity for the minor alleles (n = 21; NRS, 4.2 ± 0.8; P < .001). Only serum resistin levels showed a positive association with postoperative pain.
A genetic variant of resistin and serum resistin levels were associated with postoperative pain intensity, while other adipokines and cytokines exhibit no such association. Resistin can alter the inflammatory responses in postoperative wounds, although it could be a determinant factor that is independent of inflammatory processes. Resistin may be a novel marker for postoperative pain intensity.
与脂肪组织相关的促炎和抗炎细胞因子（脂肪因子）可以调节炎症过程，并导致代谢综合征等全身性炎症状态。在本初步研究中，我们研究了 3 种主要的脂肪因子（瘦素、脂联素和抵抗素）和 2 种非特异性促炎细胞因子（肿瘤坏死因子-α和白细胞介素-6）与术后疼痛强度的关系。
我们分析了 57 例剖腹手术后疼痛患者的脂肪因子共 45 个单核苷酸多态性。我们通过控制假发现率来调整多重检验，以降低假阳性结果的机会。在另外 36 例行剖腹手术的患者中测量了脂肪因子和促炎细胞因子的血清水平。使用这些测量值和阿片类药物剂量作为自变量进行逐步多元线性回归分析，以探讨与术后疼痛相关的因素。
只有抵抗素基因的 1 个变体（rs3745367）与术后疼痛显著相关（P <.002）。表现出纯合子次要等位基因（n = 7；数字评分量表[NRS]，2.3 ± 1.3）的患者疼痛强度低于表现出纯合子主要等位基因（n = 29；NRS，3.8 ± 1.0；P =.004）和杂合子次要等位基因（n = 21；NRS，4.2 ± 0.8；P <.001）的患者。只有血清抵抗素水平与术后疼痛呈正相关。
抵抗素的遗传变异和血清抵抗素水平与术后疼痛强度相关，而其他脂肪因子和细胞因子则没有这种关联。抵抗素可以改变术后伤口的炎症反应，尽管它可能是一个独立于炎症过程的决定因素。抵抗素可能是术后疼痛强度的一个新的标志物。
