Figure 9.

Preventive effects of pretreatment with mibefradil and NNC 55–0396, T-type Ca²⁺ channel blockers, on cyclophosphamide-induced bladder pain-like nociceptive behaviour, referred hyperalgesia and increases in bladder weight in mice. Mibefradil (Mibe) was given i.p. once 30 min before cyclophosphamide (CP; i.p., 300 mg·kg⁻¹) (left panels in A, B and C), or (Mibe x2) 30 min before and 3 h after i.p. cyclophosphamide (centre panels in A, B and C). NNC 55–0396 (20 mg·kg⁻¹) was administered i.p. once 30 min before cyclophosphamide (right panels in A, B and C). Nociceptive behaviour (A) was observed 3.5–4 h after cyclophosphamide and referred hyperalgesia was evaluated 4 h after cyclophosphamide (B). After the nociceptive tests, the mice were killed and the bladder weight was measured as an indicator of bladder oedema (C). Data show the mean with SEM for seven to eight (left panels in A, B and C), 10–14 (centre panels in A, B and C) and eight (right panels in A, B and C) mice. *P < 0.05, **P < 0.01, ***P < 0.001 versus vehicle + vehicle. †P < 0.05, ††P < 0.01, †††P < 0.001 versus vehicle + CP.