National Centre for Bowel Research, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
NIHR Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, UK.
Clin Transl Gastroenterol. 2021 Feb 22;12(2):e00313. doi: 10.14309/ctg.0000000000000313.
Despite heterogeneity, an increased prevalence of psychological comorbidity and an altered pronociceptive gut microenvironment have repeatedly emerged as causative pathophysiology in patients with irritable bowel syndrome (IBS). Our aim was to study these phenomena by comparing gut-related symptoms, psychological scores, and biopsy samples generated from a detailed diarrhea-predominant IBS patient (IBS-D) cohort before their entry into a previously reported clinical trial.
Data were generated from 42 patients with IBS-D who completed a daily 2-week bowel symptom diary, the Hospital Anxiety and Depression score, and the Patient Health Questionnaire-12 Somatic Symptom score and underwent unprepared flexible sigmoidoscopy. Sigmoid mucosal biopsies were separately evaluated using immunohistochemistry and culture supernatants to determine cellularity, mediator levels, and ability to stimulate colonic afferent activity.
Pain severity scores significantly correlated with the daily duration of pain (r = 0.67, P < 0.00001), urgency (r = 0.57, P < 0.0005), and bloating (r = 0.39, P < 0.05), but not with psychological symptom scores for anxiety, depression, or somatization. Furthermore, pain severity scores from individual patients with IBS-D were significantly correlated (r = 0.40, P < 0.008) with stimulation of colonic afferent activation mediated by their biopsy supernatant, but not with biopsy cell counts nor measured mediator levels.
Peripheral pronociceptive changes in the bowel seem more important than psychological factors in determining pain severity within a tightly phenotyped cohort of patients with IBS-D. No individual mediator was identified as the cause of this pronociceptive change, suggesting that nerve targeting therapeutic approaches may be more successful than mediator-driven approaches for the treatment of pain in IBS-D.
尽管存在异质性,但心理共病的患病率增加和促伤害性肠道微环境改变已反复成为肠易激综合征(IBS)患者的致病病理生理学。我们的目的是通过比较肠道相关症状、心理评分和来自详细腹泻型 IBS 患者(IBS-D)队列的活检样本,来研究这些现象,这些患者在进入之前报道的临床试验之前完成了为期 2 周的每日肠道症状日记、医院焦虑和抑郁评分、患者健康问卷-12 躯体症状评分,并进行了未准备的乙状结肠镜检查。使用免疫组织化学和培养上清液分别评估乙状结肠黏膜活检,以确定细胞计数、介质水平以及刺激结肠传入活动的能力。
疼痛严重程度评分与疼痛的每日持续时间(r = 0.67,P < 0.00001)、紧迫性(r = 0.57,P < 0.0005)和腹胀(r = 0.39,P < 0.05)显著相关,但与焦虑、抑郁或躯体化的心理症状评分无关。此外,IBS-D 患者的个体疼痛严重程度评分与他们的活检上清液介导的结肠传入激活刺激显著相关(r = 0.40,P < 0.008),但与活检细胞计数或测量的介质水平无关。
在严格表型 IBS-D 患者队列中,肠道周围促伤害性变化似乎比心理因素更能决定疼痛严重程度。没有确定单个介质是这种促伤害性变化的原因,这表明针对神经的治疗方法可能比针对介质的治疗方法更能成功治疗 IBS-D 的疼痛。