Ceftriaxone inhibits stress-induced bladder hyperalgesia and alters cerebral micturition and nociceptive circuits in the rat: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome research network study.
Ceftriaxone inhibits stress-induced bladder hyperalgesia and alters cerebral micturition and nociceptive circuits in the rat: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome research network study.
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DOI：
10.1002/nau.24424
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发表时间：
2020-08
影响因子：
2
通讯作者：
Rodriguez LV
中科院分区：
文献类型：
--
作者：
Holschneider DP;Wang Z;Chang H;Zhang R;Gao Y;Guo Y;Mao J;Rodriguez LV
情绪压力在间质性膀胱炎/膀胱疼痛综合征（IC/BPS）的恶化和发展中起作用。考虑到压力、焦虑和排尿所涉及的脑回路的显著重叠，以及谷氨酸在其调节中的记录作用，我们研究了谷氨酸转运增加对压力诱导的膀胱痛觉过敏的中枢放大的影响，这是IC/BPS的核心特征。将Wistar-Kyoto大鼠暴露于避水应激（WAS，1小时/天× 10天）或假应激，亚组每日给予头孢曲松（CTX），一种谷氨酸转运激活剂。然后，在膀胱灌注期间获得膀胱测压图，同时记录内脏反应（VMR）。在被动膀胱扩张期间通过静脉注射[14 C]-碘安替比林进行脑血流（CBF）绘图。在脑切片的放射自显影中定量局部CBF，并在具有统计参数映射的3D重建脑中进行分析。膀胱充盈期间，WAS引起内脏高敏感性，表现为压力阈值降低和VMR阈值触发排尿期。大脑地图显示，压力的影响，指出是响应膀胱充盈的地区。CTX降低内脏高敏感性，并减弱脊髓上排尿回路内和重叠边缘系统和伤害感受区域（包括后中线皮质（后扣带/前压后）、体感皮质和前丘脑）中的许多应激相关脑激活。CTX减少膀胱超敏反应和衰减的大脑区域，有助于伤害性和排尿电路，显示压力的影响，并已被报道证明在IC/BPS患者的功能改变。谷氨酸药理学策略调节应激相关的膀胱功能障碍可能是一种新的方法来治疗IC/BPS。
Emotional stress plays a role in the exacerbation and development of interstitial cystitis/bladder pain syndrome (IC/BPS). Given the significant overlap of brain circuits involved in stress, anxiety, and micturition, and the documented role of glutamate in their regulation, we examined the effects of an increase in glutamate transport on central amplification of stress-induced bladder hyperalgesia, a core feature of IC/BPS. Wistar-Kyoto rats were exposed to water avoidance stress (WAS, 1 hour/day × 10 days) or sham stress, with subgroups receiving daily administration of ceftriaxone (CTX), an activator of glutamate transport. Thereafter, cystometrograms were obtained during bladder infusion with visceromotor responses (VMR) recorded simultaneously. Cerebral blood flow (CBF) mapping was performed by intravenous injection of [14C]-iodoantipyrine during passive bladder distension. Regional CBF was quantified in autoradiographs of brain slices and analyzed in 3D reconstructed brains with statistical parametric mapping. WAS elicited visceral hypersensitivity during bladder filling as demonstrated by a decreased pressure threshold and VMR threshold triggering the voiding phase. Brain maps revealed stress effects in regions noted to be responsive to bladder filling. CTX diminished visceral hypersensitivity and attenuated many stress-related cerebral activations within the supraspinal micturition circuit and in overlapping limbic and nociceptive regions, including the posterior midline cortex (posterior cingulate/anterior retrosplenium), somatosensory cortex, and anterior thalamus. CTX diminished bladder hyspersensitivity and attenuated regions of the brain that contribute to nociceptive and micturition circuits, show stress effects, and have been reported to demonstrated altered functionality in IC/BPS patients. Glutamatergic pharmacologic strategies modulating stress-related bladder dysfunction may be a novel approach to the treatment of IC/BPS.
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影响因子：
3.3
作者：
Crock, Lara W.;Stemler, Kristina M.;Gereau, Robert W.
通讯作者：
Gereau, Robert W.
影响因子：
7.4
作者：
Bagarinao E;Johnson KA;Martucci KT;Ichesco E;Farmer MA;Labus J;Ness TJ;Harris R;Deutsch G;Apkarian VA;Mayer EA;Clauw DJ;Mackey S
通讯作者：
Mackey S
影响因子：
7.4
作者：
Emerson NM;Zeidan F;Lobanov OV;Hadsel MS;Martucci KT;Quevedo AS;Starr CJ;Nahman-Averbuch H;Weissman-Fogel I;Granovsky Y;Yarnitsky D;Coghill RC
通讯作者：
Coghill RC
DOI：
10.1038/npp.2008.172
发表时间：
2009-01
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
影响因子：
2.5
作者：
Coghill, RC;Sang, CN;Iadarola, MJ
通讯作者：
Iadarola, MJ