title: Effects of tramadol on viscero-visceral hyperalgesia in a rat model of endometriosis plus ureteral calculosis.
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.
authors.affiliation: 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.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Lopopolo
authors.forename: Giannapia
authors.initials: G
authors.lastname: Affaitati
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fabrizio
authors.forename: Francesca
authors.initials: F
authors.lastname: Massimini
authors.forename: Domenico
authors.initials: D
authors.lastname: Lapenna
authors.forename: Maria Adele
authors.initials: MA
authors.lastname: Giamberardino
authors.forename: Raffaele
authors.initials: R
authors.lastname: Costantini
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004715:Endometriosis / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006930:Hyperalgesia / Q000150:complications / Q000188:drug therapy*; D017207:Rats, Sprague-Dawley; D014147:Tramadol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014514:Ureteral Calculi / Q000150:complications / Q000188:drug therapy*; D059265:Visceral Pain / Q000150:complications / Q000188:drug therapy*
chemical_list: D000701:Analgesics, Opioid; D014147:Tramadol
keywords: endometriosis; rat; tramadol; ureteral calculosis; visceral pain; viscero-visceral hyperalgesia