Cyclophosphamide cystitis in mice: Behavioural characterisation and correlation with bladder inflammation

Abstract

The generation of transgenic 'knock-out' mice which lack genes relevant to pain is becoming increasing common. However, only one visceral pain model, the writhing test, is available in mice. The aim of this study was to adapt cyclophosphamide cystitis, a model of inflammatory visceral pain described in rats, for use in mice, and to characterise its behavioural effects. The toxic metabolites of systemically-administered cyclophosphamide are excreted in the urine, and induce bladder inflammation. We compared the effects of cyclophosphamide (100 and 300 mg/kg i.p., 4 h survival period) and vehicle (saline) in male mice on spontaneous behaviour (4 h continuous video-tape, and a 5-min Open Field test after 4 h). Involvement of the urinary bladder and other abdominal tissues was assessed by macroscopic examination and measurement of Evan's Blue plasma extravasation. Cyclophosphamide (300 mg/kg) produced significant changes in behaviour, including 22 +/- 6 min of 'crises' of visceral pain-related behaviour and a 53% reduction in activity, and also induced haemorrhage and substantial plasma extravasation in the bladder, but no change in other abdominal tissues. We conclude that cyclophosphamide cystitis has many advantages as a model of sub-acute, inflammatory visceral pain in mice. It does not require surgery or intubation, and we have found it to produce consistent, reproducible and quantifiable behavioural changes, which are significantly correlated with the degree of bladder inflammation in the absence of inflammation of other abdominal tissues. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.

Enterococcus faecalis Overcomes Foreign Body-Mediated Inflammation To Establish Urinary Tract Infections

“…Even though CYP-and catheter-induced inflammatory responses are not equivalent, they share some important commonalities depicted in Fig. 4B, such as bladder wall edema, mucosal damage, and host immune cell infiltration (31,32,37,38). When introduced in nonimplanted CYP-treated animals, E. faecalis is rapidly cleared from the urinary tract, similarly to saline-treated nonimplanted controls at 6 hpi (Fig.…”

Attenuation of visceral pain in mice by the essential oil from Vanillosmopsis arborea bark

“…These algogenic substances are capable of inducing pain as well as inflammatory reaction when either visceral afferents are sensitized or central neurons undergo a change in excitability (central sensitization) after persistent visceral input 10 . In the search for novel natural substances, which possess visceral antinociceptive property, we used the acute models of visceral pain induced by intraperitoneal administration of acetic acid or cyclophosphamide or by intracolonic instillation of mustard oil, capsaicin or formalin to produce spontaneous pain-related behaviors in mice, which has disease--relevancy to human irritable bowel syndrome.…”

Repeated Cold Stress Reduces Cyclophosphamide-Induced Cystitis/Bladder Pain and Macrophage Activity in Mice

“…Essentially, according to previous reports [9,10], mice received i.p. administration of CPA (Sigma-Aldrich, St. Louis, MO, USA) at 200 or 400 mg/kg, and the bladder pain and referred hyperalgesia were assessed in a transparent plastic box (23.5 × 16.6 × 12.4 cm) placed on a raised wire mesh 3.5-4 h after the CPA treatment.…”

“…RC-stressed animals thus appear to exhibit distinct susceptibility to different external stimuli. Cyclophosphamide (CPA) causes inflammatory bladder pain accompanying cystitis in rodents [9], which involves complicated neuronal mechanisms including the increased activity of Ca v 3.2 T-type Ca 2+ channels [10] and the receptor for advanced glycation end products (RAGE) [11]. The CPA-treated animals appear to mimic many symptoms including bladder pain in patients with interstitial cystitis, which become worse during periods of stress [12].…”