Characterization of Cyclophosphamide Cystitis, a Model of Visceral and Referred Pain, in the Mouse: Species and Strain Differences

Abstract

Existing animal models of visceral pain in the mouse are of limited practical usefulness since they are labor intensive or not visceral specific. Recently a rat model of cyclophosphamide (CP) cystitis was developed that requires only intraperitoneal injection and features inflammation confined to the bladder. We adapted this model for use in multiple mouse strains to investigate the genetic basis of variability in visceral nociception. Outbred CD-1 mice and 12 inbred mouse strains were tested for behavioral changes induced by CP (0 to 300 mg/kg intraperitoneally). We noted that despite the absence of postural changes or abdominal crises in CD-1 mice, CP produced dose dependent decreases in voluntary locomotor activity unaccompanied by ataxia measured on the rotarod test; referred hyperalgesia of the tail base region but not of the hind paw, which was inhibited in dose dependent fashion by morphine (0 to 20 mg/kg); and bladder inflammation corresponding to these behavioral indices. Furthermore, the extent of hypolocomotion was genotype dependent across 12 inbred strains. The simple and automatable nature of CP cystitis using hypolocomotion as a dependent measure renders it an attractive model in which to investigate the genetic and physiological bases of visceral pain. Comparison of strain sensitivity to CP induced hypolocomotion with other nociceptive assays suggests that genes specific to visceral nociception may exist.