Abstract：
The etiology of interstitial cystitis/bladder pain syndrome (IC/BPS) is unknown but likely multifactorial. IC/BPS symptoms can be exacerbated by psychological stress, but underlying mechanisms remain to be defined. TRPV1 channels, expressed on nerve fibers, have been implicated in bladder dysfunction and colonic hypersensitivity with stress in rodents. Histamine/H1R activation of TRPV1+ nerves increases bladder afferent fiber sensitivity to distension. TRPV1 channels are also expressed on mast cells, previously implicated in contributing to IC/BPS etiology and symptoms. We have examined the contribution of TRPV1 and mast cells to bladder dysfunction after repeated variate stress (RVS). RVS increased (p ≤ 0.05) serum and fecal corticosterone expression and induced anxiety-like behavior in wild type (WT) mice. Intravesical instillation of the selective TRPV1 antagonist capsazepine (CPZ) rescued RVS-induced bladder dysfunction in WT mice. Trpv1 knockout (KO) mice did not increase voiding frequency with RVS and did not exhibit increased serum corticosterone expression despite exhibiting anxiety-like behavior. Mast cell deficient mice (B6.Cg-Kitw-sh) failed to demonstrate RVS-induced increased voiding frequency or serum corticosterone expression whereas control (no stress) mast cell deficient mice had similar functional bladder capacity to WT mice. TRPV1 protein expression was significantly increased in the rostral lumbar (L1-L2) spinal cord and dorsal root ganglia in WT mice exposed to RVS but no changes were observed in lumbosacral (L6-S1) spinal segments or DRG. These studies demonstrated TRPV1 and mast cell involvement in RVS-induced increased voiding frequency and suggest that TRPV1 and mast cells may be useful targets to mitigate stress-induced urinary bladder dysfunction.
摘要：
间质性膀胱炎/膀胱疼痛综合征（IC/BPS）的病因未知，但可能是多因素的。IC/BPS症状可因心理压力而加剧，但潜在的机制仍有待定义。TRPV1通道,在神经纤维上表达，与啮齿动物的膀胱功能障碍和结肠超敏反应有关。TRPV1+神经的组胺/H1R激活增加膀胱传入纤维对扩张的敏感性。TRPV1通道也在肥大细胞上表达，以前与IC/BPS病因和症状有关。我们已经检查了TRPV1和肥大细胞在反复变化应激（RVS）后对膀胱功能障碍的贡献。在野生型（WT）小鼠中，RVS增加（p≤0.05）血清和粪便皮质酮表达并诱导焦虑样行为。膀胱内滴注选择性TRPV1拮抗剂capsazepine（CPZ）可挽救WT小鼠中RVS诱导的膀胱功能障碍。Trpv1敲除（KO）小鼠尽管表现出焦虑样行为，但RVS并未增加排尿频率，也未表现出血清皮质酮表达增加。肥大细胞缺陷小鼠(B6。Cg-Kitw-sh）未能证明RVS诱导的排尿频率或血清皮质酮表达增加，而对照（无应激）肥大细胞缺陷小鼠的膀胱功能与WT小鼠相似。在暴露于RVS的WT小鼠中，TRPV1蛋白在头端腰（L1-L2）脊髓和背根神经节中的表达显着增加，但在腰骶段（L6-S1）脊髓节段或DRG中未观察到变化。这些研究表明TRPV1和肥大细胞参与RVS诱导的排尿频率增加，并表明TRPV1和肥大细胞可能是缓解应激诱导的膀胱功能障碍的有用靶标。
