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.