ZD 7288，一种HCN通道阻滞剂，可减轻肠易激综合征样大鼠的慢性内脏疼痛。
ZD 7288, an HCN channel blocker, attenuates chronic visceral pain in irritable bowel syndrome-like rats.
作者信息
Chen Yu, Lin Chun, Tang Ying, Chen Ai-Qin, Liu Cui-Ying, Lu Da-Li
机构信息
Yu Chen, Chun Lin, Ying Tang, Ai-Qin Chen, Cui-Ying Liu, Da-Li Lu, Laboratory for Pain Research, Key Laboratory of Brain Aging and Neurodegenerative Diseases, Center for Neuroscience Research, Department of Physiology and Pathophysiology, Fujian Medical University, Fuzhou 350108, Fujian Province, China.
出版信息
World J Gastroenterol. 2014 Feb 28;20(8):2091-7. doi: 10.3748/wjg.v20.i8.2091.
AIM
To investigate the effects of ZD 7288, a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker, on rats with chronic visceral pain.
METHODS
Rats with visceral hypersensitivity were generated using neonatal colon irritation during postnatal days 8-15 as described previously. Visceral hypersensitivity was evaluated using electromyographic (EMG) responses of abdominal external oblique muscles to 20-80 mmHg colorectal distentions (CRD). Abdominal withdrawal reflex (AWR) scores and pain thresholds were also detected in adult rats. Different doses of ZD 7288 (25, 50, and 100 nmol/L) were intrathecally administered in rats to study the role of spinal HCN channel in chronic visceral hypersensitivity.
RESULTS
EMG responses to 20-80 mmHg CRD and AWR scores under 20-60 mmHg CRD significantly increased in rats with visceral hypersensitivity compared to control rats (P < 0.05). The pain threshold in rats with visceral hypersensitivity significantly decreased compared to control rats (P < 0.05). Treatment with 50-100 nmol/L ZD 7288 significantly inhibited EMG responses (16%-62%, 80-20 mmHg CRD, P < 0.05) and AWR scores (24%-37%, 40-20 mmHg CRD, P < 0.05; 12%-61%, 80-20 mmHg CRD, P < 0.05, respectively), and significantly increased pain thresholds (32%-77%, P < 0.05).
CONCLUSION
Spinal HCN channels may play an important role in chronic visceral hypersensitivity.
目的
研究超极化激活的环核苷酸门控（HCN）通道阻滞剂ZD 7288对慢性内脏痛大鼠的影响。
方法
如前所述，在出生后第8 - 15天对新生大鼠进行结肠刺激以建立内脏高敏性大鼠模型。使用腹外斜肌的肌电图（EMG）对20 - 80 mmHg结肠扩张（CRD）的反应来评估内脏高敏性。还检测成年大鼠的腹部退缩反射（AWR）评分和疼痛阈值。将不同剂量的ZD 7288（25、50和100 nmol/L）鞘内注射到大鼠体内，以研究脊髓HCN通道在慢性内脏高敏性中的作用。
结果
与对照大鼠相比，内脏高敏性大鼠对20 - 80 mmHg CRD的EMG反应以及20 - 60 mmHg CRD下的AWR评分显著增加（P < 0.05）。与对照大鼠相比，内脏高敏性大鼠的疼痛阈值显著降低（P < 0.05）。用50 - 100 nmol/L ZD 7288治疗可显著抑制EMG反应（16% - 62%，80 - 20 mmHg CRD，P < 0.05）和AWR评分（24% - 37%，40 - 20 mmHg CRD，P < 0.05；12% - 61%，80 - 20 mmHg CRD，P < 0.05），并显著提高疼痛阈值（32% - 77%，P < 0.05）。
结论
脊髓HCN通道可能在慢性内脏高敏性中起重要作用。
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