Ji Guangchen, Fu Yu, Ruppert Katherine A, Neugebauer Volker
Department of Neuroscience and Cell Biology, The University of Texas Medical Branch, Galveston, Texas 77555-1069, USA.
Mol Pain. 2007 Jun 5;3:13. doi: 10.1186/1744-8069-3-13.
Corticotropin-releasing factor receptor CRF1 has been implicated in the neurobiological mechanisms of anxiety and depression. The amygdala plays an important role in affective states and disorders such as anxiety and depression. The amygdala is also emerging as a neural substrate of pain affect. However, the involvement of the amygdala in the interaction of pain and anxiety remains to be determined. This study tested the hypothesis that CRF1 receptors in the amygdala are critically involved in pain-related anxiety. Anxiety-like behavior was determined in adult male rats using the elevated plus maze (EPM) test. The open-arm preference (ratio of open arm entries to the total number of entries) was measured. Nocifensive behavior was assessed by measuring hindlimb withdrawal thresholds for noxious mechanical stimulation of the knee. Measurements were made in normal rats and in rats with arthritis induced in one knee by intraarticular injections of kaolin/carrageenan. A selective CRF1 receptor antagonist (NBI27914) or vehicle was administered systemically (i.p.) or into the central nucleus of the amygdala (CeA, by microdialysis). The arthritis group showed a decreased preference for the open arms in the EPM and decreased hindlimb withdrawal thresholds. Systemic or intraamygdalar (into the CeA) administration of NBI27914, but not vehicle, inhibited anxiety-like behavior and nocifensive pain responses, nearly reversing the arthritis pain-related changes. This study shows for the first time that CRF1 receptors in the amygdala contribute critically to pain-related anxiety-like behavior and nocifensive responses in a model of arthritic pain. The results are a direct demonstration that the clinically well-documented relationship between pain and anxiety involves the amygdala.
促肾上腺皮质激素释放因子受体CRF1与焦虑和抑郁的神经生物学机制有关。杏仁核在诸如焦虑和抑郁等情感状态及障碍中发挥着重要作用。杏仁核也正成为疼痛情感的神经基础。然而，杏仁核在疼痛与焦虑相互作用中的作用仍有待确定。本研究检验了这样一个假设，即杏仁核中的CRF1受体在与疼痛相关的焦虑中起关键作用。使用高架十字迷宫（EPM）试验测定成年雄性大鼠的焦虑样行为。测量开放臂偏好（开放臂进入次数与总进入次数的比率）。通过测量对膝盖有害机械刺激的后肢退缩阈值来评估伤害防御行为。在正常大鼠以及通过关节内注射高岭土/角叉菜胶诱导一侧膝盖患关节炎的大鼠中进行测量。选择性CRF1受体拮抗剂（NBI27914）或赋形剂通过全身（腹腔注射）或注入杏仁核中央核（通过微透析注入CeA）给药。关节炎组在EPM中对开放臂的偏好降低，后肢退缩阈值降低。全身或杏仁核内（注入CeA）给予NBI27914而非赋形剂可抑制焦虑样行为和伤害防御性疼痛反应，几乎逆转了与关节炎疼痛相关的变化。本研究首次表明，在关节炎疼痛模型中，杏仁核中的CRF1受体对与疼痛相关的焦虑样行为和伤害防御反应起关键作用。结果直接证明了临床上充分记录的疼痛与焦虑之间的关系涉及杏仁核。
