Pathophysiology of Pain Laboratory, Ce.S.I, "G. D'Annunzio" Foundation, via dei Vestini s.n., 66013, Chieti Scalo (Chieti), Italy; Department of Medicine and Science of Aging, University of Chieti, via dei Vestini s.n., 66013, Chieti Scalo (Chieti), Italy.
Fundam Clin Pharmacol. 2014 Jun;28(3):331-41. doi: 10.1111/fcp.12038. Epub 2013 Jun 21.
The effects of tramadol versus placebo administration on behavioral indicators of ureteral pain, pelvic pain and referred lumbar muscle hyperalgesia were investigated in a rat model of viscero-visceral hyperalgesia from endometriosis plus ureteral calculosis (endo + stone). Fifty female Sprague-Dawley rats underwent surgical induction of endometriosis and, 2 weeks later, were randomly assigned to five groups (10 each), to be treated i.p., twice a day, with tramadol (0.625, 1.25, 2.5, or 5 mg/kg) or saline for 5 days (14-18th day postendometriosis; prestone treatment). On the 21st day, they underwent laparotomy for stone formation in the upper left ureter (dental cement injection). All were video-taped 24 h nonstop for 7 days before and 4 days after stone formation (14-25th day postendometriosis) to record ureteral and pelvic pain behaviors. Lumbar sensitivity (L1) was tested bilaterally, daily over the same period, by verifying presence/absence of vocalization upon muscle pinching at a predefined pressure (calibrated forceps). Additional fifty endo + stone rats underwent the same protocol, except that treatment was performed on 21st-25th day (poststone treatment). Tramadol vs. saline significantly reduced number and duration of ureteral crises, duration of pelvic behavior, and incidence of muscle hyperalgesia (P < 0.0001), with a dose-dependent effect. Prestone treatment was significantly more effective than poststone treatment for the 1.25 dose for all parameters and 2.5 dose for pelvic and muscle parameters (0.003 > P < 0.02). Tramadol, even at low doses, is thus highly protective against pain from 'viscero-visceral hyperalgesia' in endometriosis plus ureteral calculosis; it can represent a valid therapeutic approach in women with these comorbidities.
本研究旨在探讨曲马多（tramadol）与安慰剂对子宫内膜异位症合并输尿管结石（endo+stone）大鼠内脏-内脏痛觉过敏模型的输尿管痛觉、盆腔痛觉和牵涉性腰大肌痛觉的行为学指标的影响。50 只雌性 Sprague-Dawley 大鼠接受了手术诱导的子宫内膜异位症，2 周后，随机分为五组（每组 10 只），每天两次腹腔注射曲马多（0.625、1.25、2.5 或 5mg/kg）或生理盐水，共 5 天（endo 后第 14-18 天；prestone 治疗）。第 21 天，大鼠接受左上输尿管结石形成的剖腹手术（牙用水泥注射）。在结石形成前（endo 后第 14-25 天）和形成后（14-25 天）的 7 天内，对所有大鼠进行 24 小时不间断的视频记录，以记录输尿管和盆腔痛觉行为。在同一时期内，通过双侧腰大肌肌肉夹捏（校准的钳子）验证有无发声来检测腰大肌的敏感性（L1），每日检测一次。另外 50 只 endo+stone 大鼠接受了相同的方案，但治疗时间为 21-25 天（poststone 治疗）。与生理盐水相比，曲马多显著减少了输尿管危象的次数和持续时间、盆腔行为的持续时间以及肌肉痛觉过敏的发生率（P<0.0001），且呈剂量依赖性。与 poststone 治疗相比，prestone 治疗对所有参数的 1.25 剂量和盆腔及肌肉参数的 2.5 剂量更为有效（0.003>P<0.02）。因此，即使低剂量的曲马多也能高度预防子宫内膜异位症合并输尿管结石引起的“内脏-内脏痛觉过敏”；对于患有这些合并症的女性，它可能是一种有效的治疗方法。
