Ex Situ-En BlockandIn VitroAnimal Models of Mechanosensory and Motor Equivalents of Pelvic and Urogenital Pain

Pelvic pain is a complex painful sensation caused by spasm/distension/inflammation in hollow organs, with still unclear mechanisms. The aim of this study was to develop and validate an en block—ex situ mouse model resembling the conditions of painful distension of the urinary system and an in vitro rat model resembling uterine contractions in conditions of hormonal simulation of dysmenorrhea. The effects of Metamizol (Analgin) were studied in test experiments in order to validate the experimental potential of the novel en block—ex situ and in vitro models. Mature male mice (27.8 g ± 0.4 g b.m.) and female Wistar rats (180 g ± 5 g b.m.) were used. (i) The lumbar-sacral portion of spine and pelvis with whole urinary system (kidneys, ureters, urinary bladder, urethra) and surrounding tissues were dissected en block, placed in an organ chamber and bathed with tissue medium. The effect of Metamizol (0.25 mmol/L) on sensory nerve firing during rapid distension of urinary bladder was studied. (ii) Anesthetized rats were ovariectomized via ventral approach. Postoperatively, the animals were implanted with matrix-driven delivery system (MDDS) containing Levonorgestrel (1.05 mg) or placebo. MDDS was removed after 4 days (hormone withdrawal) or 7 days (placebo application). The middle part of the uterine horns was excised and placed between two platinum ring electrodes near the outlet of a 1 mL plastic double-jacketed horizontal tissue chamber. The preparation was tied to a force-displacement transducer for registration of isometric changes of tension. Electric stimulation was applied to elicit myogenic motor responses. Metamizol (0.5 mmol/L) was applied in vitro. The in vitro results showed that Metamizol suppressed the spontaneous, as well as the electrical field stimulation evoked and PGF2α- induced contractions of isolated uterine horn. Metamizol alleviated the firing of pelvic nerve afferents due to bladder distension and/or intravesical application of ATP, but did not change the distension induced release of ATP. The results revealed a therapeutic potential of Metamizol in alleviation of pain in painful pelvic syndromes in humans.