Introduction: Interstitial Cystitis (IC) is a chronic urological disorder characterized by pain urinary urgency, frequency and nocturia. Not all patients are responsive to existing treatments which are also limited by side-effects. As such new treatments with novel mechanisms of action are needed. Sunobinop (V117957) is a selective partial agonist of the nociceptin/orphanin-FQ (N/OFQ) peptide receptor which is excreted unchanged by the kidneys. The objective of these studies was to examine the effect of sunobinop on visceral pain in a model of interstitial cystitis in female rats. Methods: Female Sprague-Dawley rats (10/group) were administered sunobinop (30 mg/kg, p.o.), ibuprofen (300 mg/kg, p.o.) or vehicle and 5 minutes later a single dose of cyclophosphamide (CYP; 150 mg/kg i.p). Tactile sensitivity (von Frey fibers) was measured at baseline, 2, 3, 4 and 24 hr after CYP. Parameters analyzed were nociceptive threshold (g), nociceptive scores (%) and area under the nociception curve (AUC) across two fiber ranges (1-6 g and 6-26 g) all of which were expressed as mean ± standard error of the mean (SEM) with significance set at p=0.05. Results: At all evaluated time points CYP induced a significant decrease of nociception measures as compared to saline (p < 0.0001) indicating successful model development. Ibuprofen-treated rats displayed a significant overall increase in nociceptive thresholds and significantly decreased nociceptive scores and AUC measures as compared to vehicle (p < 0.0001). Post hoc statistical analysis showed a slight and gradual decrease of ibuprofen effect was observed over time. Sunobinop produced an overall inhibitory effect on nociceptive thresholds (significant at 3 hr), a significant decrease in nociceptive scores and a significant decrease in AUCs starting from 2h and up to 24h after CYP injection (p < 0.01). After 3h, efficacy of sunobinop decreased slightly and gradually over time. Conclusions: The positive control, ibuprofen, significantly decreased pain responses, as compared to vehicle in an acute model of CYP induced IC. Likewise, sunobinop was significantly anti-nociceptive. As such this data suggests sunobinop has potential utility in treatment of pain associated with IC. SOURCE OF Funding: Imbrium Therapeutics L.P. a subsidiary of Purdue Pharmaceuticals L.P.
