Zubieta Jon-Kar, Smith Yolanda R, Bueller Joshua A, Xu Yanjun, Kilbourn Michael R, Jewett Douglas M, Meyer Charles R, Koeppe Robert A, Stohler Christian S
Department of Psychiatry and Mental Health Research Institute, University of Michigan, Ann Arbor, Michigan 48109-0720, USA.
J Neurosci. 2002 Jun 15;22(12):5100-7. doi: 10.1523/JNEUROSCI.22-12-05100.2002.
Sex differences in the experience of clinical and experimental pain have been reported. However, the neurobiological sources underlying the variability in pain responses between sexes have not been adequately explored, especially in humans. The endogenous opioid neurotransmitters and mu-opioid receptors are centrally implicated in responses to stress, in the suppression of pain, and in the action of opiate analgesic drugs. Here we examined sex differences in the activation of the mu-opioid system in response to an intensity-controlled sustained deep-tissue pain challenge with positron emission tomography and a mu-opioid receptor-selective radiotracer. Twenty-eight young healthy volunteers (14 men and 14 women) were studied during saline control and pain conditions using a double-blind, randomized, and counterbalanced design. Women were scanned during the early follicular phase of their menstrual cycles after ovulatory cycles. Significant sex differences in the regional activation of the mu-opioid system in response to sustained pain were detected compared with saline controls. Men demonstrated larger magnitudes of mu-opioid system activation than women in the anterior thalamus, ventral basal ganglia, and amygdala. Conversely, women demonstrated reductions in the basal state of activation of the mu-opioid system during pain in the nucleus accumbens, an area previously associated with hyperalgesic responses to the blockade of opioid receptors in experimental animals. These data demonstrate that at matched levels of pain intensity, men and women during their follicular phase differ in the magnitude and direction of response of the mu-opioid system in distinct brain nuclei.
已有报道称临床疼痛和实验性疼痛的体验存在性别差异。然而，性别之间疼痛反应变异性的神经生物学根源尚未得到充分探索，尤其是在人类中。内源性阿片类神经递质和μ-阿片受体在应激反应、疼痛抑制以及阿片类镇痛药的作用中起着核心作用。在此，我们使用正电子发射断层扫描和一种μ-阿片受体选择性放射性示踪剂，研究了在强度可控的持续性深部组织疼痛刺激下，μ-阿片系统激活的性别差异。采用双盲、随机和平衡设计，对28名年轻健康志愿者（14名男性和14名女性）在生理盐水对照和疼痛条件下进行了研究。在排卵周期后的月经周期卵泡早期对女性进行扫描。与生理盐水对照相比，在对持续性疼痛的反应中，检测到μ-阿片系统区域激活存在显著性别差异。在丘脑前部、腹侧基底神经节和杏仁核中，男性的μ-阿片系统激活程度大于女性。相反，在伏隔核中，女性在疼痛期间μ-阿片系统的基础激活状态降低，该区域先前与实验动物中阿片受体阻断后的痛觉过敏反应有关。这些数据表明，在疼痛强度匹配的水平下，处于卵泡期的男性和女性在不同脑核中μ-阿片系统反应的程度和方向存在差异。
