Figure 8.

Somatic sensitivity of hindpaw and pelvic region in female mice is increased with CYP treatment and reduced with intravesical instillation of the CXCR3 receptor antagonist, AMG487 (5 mg/kg). Somatic sensitivity testing of the hindpaw (A) and pelvic regions (B) with von Frey filaments in control (closed triangles) mice with vehicle, mice treated with CYP (4 h; closed squares) and vehicle, CYP treated (4 h) mice with intravesical instillation of a CXCR3 receptor antagonist, AMG487 (5 mg/kg; open squares) and control (open triangles) mice with intravesical infusion of AMG487 (5 mg/kg). The von Frey filaments were applied in an up-down method for 1–3 s with an interstimulus interval of 15 s. A positive response to hindpaw stimulation was sharp withdrawal of the paw or licking of the tested hindpaw. For pelvic region stimulation, stimulation was confined to the lower abdominal area overlying the urinary bladder. The following behaviors were considered positive responses to pelvic region stimulation: sharp retraction of the abdomen, jumping, or immediate licking or scratching of the pelvic area. Mice treated acutely (4 h) with CYP and vehicle had a significantly (*p ≤ 0.01) increased hindpaw response frequency with filaments of greater force (1 g, 4 g) (A) and pelvic response frequency (B) with all von Frey filaments (0.1–4 g) tested compared to control mice (no CYP + vehicle). Mice treated acutely (4 h) with CYP and intravesical infusion of AMG487 had a significantly (bracket with ^#p ≤ 0.01) reduced hindpaw response frequency with filaments of greater force (1 g, 4 g) (A) and pelvic response frequency (B) with all von Frey filaments (0.1–4 g) tested compared to CYP (4 h + vehicle). Although somatic sensitivity in the hindpaw and pelvic region were significantly (p ≤ 0.01) reduced in female mice with CYP-induced cystitis and AMG487 treatment, this effect was only partial because somatic sensitivity in these mice was still significantly (p ≤ 0.01) greater than that in control + AMG487 at greater forces evaluated (A,B). No differences in hindpaw (A) or pelvic sensitivity (B) were detected between control mice treated with vehicle and control mice treated with AMG487. Hindpaw or pelvic sensitivity testing with calibrated von Frey filaments was determined in separate groups of female mice. All somatic testing was performed in a blinded manner and decoded after testing for analyses. Sample sizes are n = 10 for each group; *p ≤ 0.01.