Hernandez Siomara, Cruz Myrella L, Seguinot Inevy I, Torres-Reveron Annelyn, Appleyard Caroline B
1 Physiology Division, Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce, PR, USA.
2 Microbiology Division, Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce, PR, USA.
Reprod Sci. 2017 Oct;24(10):1371-1381. doi: 10.1177/1933719116687655. Epub 2017 Jan 17.
Pain in patients with endometriosis is considered a significant source of stress but does not always correlate with severity of the condition. We have demonstrated that stress can worsen endometriosis in an animal model. Here, we tested the impact of a psychological stress protocol on pain thresholds and pain receptors.
Endometriosis was induced in female rats by suturing uterine horn tissue next to the intestinal mesentery. Sham rats had sutures only. Rats were exposed to water avoidance stress for 7 consecutive days or handled for 5 minutes (no stress). Fecal pellets and serum corticosterone (CORT) levels were measured as an index of anxiety. Pain perception was assessed using hot plate and Von Frey tests. Substance P, enkephalin, endomorphin-2, Mu opioid receptor (MOR), and neurokinin-1 receptor expression in the spinal cord were measured by immunohistochemistry.
Fecal pellets and CORT were significantly higher in the endo-stress (ES) group than endo-no stress (ENS; P < .01) and sham-no stress groups (SNS; P < .01). The ES rats had more colonic damage ( P < .001 vs SNS; P < .05 vs ENS), vesicle mast cell infiltration ( P < .01 vs ENS), and more severe vesicles than ENS. The ES developed significant hyperalgesia ( P < .05) but stress reversed the allodynic effect caused by endo ( P < .001). The MOR expression was significantly reduced in ENS versus SNS ( P < .05) and more enkephalin expression was found in endo groups.
Animals subjected to stress develop more severe symptoms but interestingly stress seems to have beneficial effects on abdominal allodynia, which could be a consequence of the stress-induced analgesia phenomenon.
子宫内膜异位症患者的疼痛被认为是压力的重要来源,但并不总是与病情严重程度相关。我们已经证明,压力会在动物模型中使子宫内膜异位症恶化。在此,我们测试了一种心理应激方案对疼痛阈值和疼痛感受器的影响。
通过将子宫角组织缝合在肠系膜旁诱导雌性大鼠患子宫内膜异位症。假手术大鼠仅进行缝合。大鼠连续7天暴露于避水应激或处理5分钟(无应激)。测量粪便颗粒和血清皮质酮(CORT)水平作为焦虑指标。使用热板法和von Frey试验评估疼痛感知。通过免疫组织化学测量脊髓中P物质、脑啡肽、内吗啡肽-2、μ阿片受体(MOR)和神经激肽-1受体的表达。
内异应激(ES)组的粪便颗粒和CORT显著高于内异无应激(ENS)组(P <.01)和假手术无应激组(SNS)(P <.01)。ES组大鼠的结肠损伤更多(与SNS组相比,P <.001;与ENS组相比,P <.05),膀胱肥大细胞浸润更多(与ENS组相比,P <.01),且膀胱比ENS组更严重受损。ES组出现显著的痛觉过敏(P <.05),但应激逆转了内异症引起的异常性疼痛效应(P <.001)。与SNS组相比,ENS组的MOR表达显著降低(P <.05),在内异症组中发现更多的脑啡肽表达。
遭受应激的动物会出现更严重的症状,但有趣的是,应激似乎对腹部异常性疼痛有有益影响,这可能是应激诱导镇痛现象的结果。