Chen Yu, Lin Chun, Tang Ying, Chen Ai-Qin, Liu Cui-Ying, Lu Da-Li
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.
World J Gastroenterol. 2014 Feb 28;20(8):2091-7. doi: 10.3748/wjg.v20.i8.2091.
To investigate the effects of ZD 7288, a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker, on rats with chronic visceral pain.
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.
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).
Spinal HCN channels may play an important role in chronic visceral hypersensitivity.
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。
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。
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）。
脊髓HCN通道可能在慢性内脏高敏性中起重要作用。
