Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Osher Center for Integrative Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Osher Center for Integrative Medicine, Karolinska Institutet, Stockholm, Sweden; Stress Research Institute, Stockholm University, Stockholm, Sweden.
Brain Behav Immun. 2015 May;46:35-43. doi: 10.1016/j.bbi.2014.11.014. Epub 2014 Dec 5.
Systemic inflammation can induce pain hypersensitivity in animal and human experimental models, and has been proposed to be central in clinical pain conditions. Women are overrepresented in many chronic pain conditions, but experimental studies on sex differences in pain regulation during systemic inflammation are still scarce. In two randomized and double blind placebo controlled experiments, we used low doses of lipopolysaccharide (LPS) as an experimental model of systemic inflammation. The first study employed 0.8ng/kg LPS in a within-subject design of 8 individuals (1 woman), and the second study 0.6ng/kg LPS in a between-subject design of 52 participants (29 women). We investigated the effect on (a) pressure, heat, and cold pain thresholds, (b) suprathreshold noxious heat and cold sensitivity, and (c) conditioned pain modulation (CPM), and differences between men and women. LPS induced significantly lower pressure pain thresholds as compared to placebo (mean change with the 0.8ng/kg dose being -64±30kPa P=.04; with the 0.6ng/kg dose -58±55kPa, P<.01, compared to before injection), whereas heat and cold pain thresholds remained unaffected (P's>.70). Suprathreshold noxious pain was not affected by LPS in men (P's⩾.15). However, LPS made women rated suprathreshold noxious heat stimuli as more painful (P=.01), and showed a tendency to rate noxious cold pain as more painful (P=.06) as compared to placebo. Furthermore, LPS impaired conditioned pain modulation, a measure of endogenous pain inhibition, but this effect was also restricted to women (P<.01, for men P=.27). Pain sensitivity correlated positively with plasma IL-6 and IL-8 levels. The results show that inflammation more strongly affects deep pain, rather than cutaneous pain, and suggest that women's pain perception and modulation is more sensitive to immune activation than men's.
全身炎症可在动物和人类实验模型中诱导痛觉过敏，并被认为与临床疼痛状况有关。许多慢性疼痛疾病中女性的患病率更高，但关于全身炎症期间疼痛调节的性别差异的实验研究仍然很少。在两项随机双盲安慰剂对照实验中，我们使用低剂量脂多糖（LPS）作为全身炎症的实验模型。第一项研究采用 0.8ng/kg LPS 进行 8 名个体（1 名女性）的个体内设计，第二项研究采用 0.6ng/kg LPS 进行 52 名参与者（29 名女性）的个体间设计。我们研究了 LPS 对（a）压力、热和冷痛阈值、（b）超阈值有害热和冷敏感性以及（c）条件性疼痛调制（CPM）的影响，并研究了男女之间的差异。与安慰剂相比，LPS 显著降低了压力痛阈值（用 0.8ng/kg 剂量时的平均变化为-64±30kPa，P=.04；用 0.6ng/kg 剂量时为-58±55kPa，P<.01，与注射前相比），而热和冷痛阈值不受影响（P>.70）。在男性中，LPS 对超阈值有害疼痛没有影响（P's>.15）。然而，LPS 使女性对超阈值有害热刺激的评价更痛（P=.01），并且表现出对有害冷痛的评价更痛的趋势（P=.06）与安慰剂相比。此外，LPS 损害了条件性疼痛调制，这是一种内源性疼痛抑制的测量，但这种影响也仅限于女性（P<.01，男性 P=.27）。疼痛敏感性与血浆 IL-6 和 IL-8 水平呈正相关。结果表明，炎症对深部疼痛的影响大于对皮肤疼痛的影响，并提示女性的疼痛感知和调制对免疫激活的敏感性高于男性。
