DeBerry Jennifer J, Robbins Meredith T, Ness Timothy J
Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Psychology, University of Alabama at Birmingham, Birmingham, AL, USA.
Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Psychology, University of Alabama at Birmingham, Birmingham, AL, USA.
Brain Res. 2015 May 5;1606:77-85. doi: 10.1016/j.brainres.2015.01.008. Epub 2015 Feb 17.
Chronic stress has been implicated in the pathogenesis of chronic visceral pain conditions, such as interstitial cystitis (IC), and bouts of acute stress exacerbate clinical urological pain. Studies using animal models have shown that exposure to chronic footshock stress augments reflex responses to urinary bladder distension (UBD) in animal models, however acute effects in animal models are largely unknown, as are the central nervous system mechanisms of stress-related increases in nociception. The amygdala is a salient structure for integration of sensory and cognitive/emotional factors. The present study determined the role of the central nucleus of the amygdala (CeA) in stress-related bladder hypersensitivity. We examined the effects of CeA manipulations (lesions and chemical stimulation) on visceromotor responses (abdominal muscle contractions) to UBD in adult, female Sprague-Dawley rats. We report that acute footshock stress produces bladder hyperalgesia that can be prevented by bilateral CeA lesions, despite no effect of lesions on baseline somatic sensation, as indicated by flinch/jump thresholds to electrical shock. Further, acute glucocorticoid stimulation of the CeA recapitulated stress-induced hyperalgesia. Of note is that CeA lesions, but not chemical stimulation, significantly affected HPA axis activation, as indicated by measurements of circulating corticosterone. Our findings conclusively show that the CeA is necessary for the generation of bladder hyperalgesia in response to acute stress. The CeA may play multiple stress-related roles in nociceptive modulation, i.e., via direct facilitation of the HPA axis during acute stress, or via modulation of other systems that augment acute stress responsiveness.
慢性应激与慢性内脏疼痛性疾病的发病机制有关，如间质性膀胱炎（IC），急性应激发作会加剧临床泌尿外科疼痛。使用动物模型的研究表明，在动物模型中，长期足部电击应激会增强对膀胱扩张（UBD）的反射反应，然而，动物模型中的急性效应在很大程度上尚不清楚，与应激相关的痛觉增加的中枢神经系统机制也不清楚。杏仁核是整合感觉和认知/情感因素的一个重要结构。本研究确定了杏仁核中央核（CeA）在应激相关膀胱超敏反应中的作用。我们研究了CeA操作（损伤和化学刺激）对成年雌性Sprague-Dawley大鼠对UBD的内脏运动反应（腹肌收缩）的影响。我们报告，急性足部电击应激会产生膀胱痛觉过敏，双侧CeA损伤可预防这种过敏，尽管损伤对基线躯体感觉没有影响，电击的退缩/跳跃阈值表明了这一点。此外，对CeA进行急性糖皮质激素刺激可重现应激诱导的痛觉过敏。值得注意的是，如循环皮质酮的测量所示，CeA损伤而非化学刺激显著影响HPA轴激活。我们的研究结果确凿地表明，CeA是急性应激反应中膀胱痛觉过敏产生所必需的。CeA可能在伤害性调制中发挥多种与应激相关的作用，即通过在急性应激期间直接促进HPA轴，或通过调节其他增强急性应激反应性的系统。
