Effects of tramadol on viscero‐visceral hyperalgesia in a rat model of endometriosis plus ureteral calculosis

Mariangela Lopopolo, Giannapia Affaitati, Alessandra Fabrizio, Francesca Massimini, Domenico Lapenna, Maria Adele Giamberardino, Raffaele Costantini
Fundamental & clinical pharmacology · 2013 · vol. 28(3) , pp. 331–341 · doi:10.1111/fcp.12038 · PMID:23786290 · W2013356266
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Tramadol administration significantly reduced ureteral pain, pelvic pain, and muscle hyperalgesia in rats with endometriosis and ureteral stones, with a dose-dependent effect and greater efficacy when given before stone formation.

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Abstract

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.

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Condition tags

endometriosis

MeSH descriptors

Analgesics, Opioid Endometriosis Hyperalgesia Tramadol Ureteral Calculi Visceral Pain Analgesics, Opioid Analgesics, Opioid Analgesics, Opioid Animals Behavior, Animal Behavior, Animal Disease Models, Animal Dose-Response Relationship, Drug Endometriosis Endometriosis Female Hyperalgesia Hyperalgesia Rats, Sprague-Dawley

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