You H J, Mørch C D, Chen J, Arendt-Nielsen L
Center for Sensory-Motor Interaction, Laboratory for Experimental Pain Research, Aalborg University, Fredrik Bajers Vej 7D-3, DK-9220, Aalborg, Denmark.
Neuroscience. 2003;121(2):459-72. doi: 10.1016/s0306-4522(03)00296-3.
The aim of present study was to examine the effect of a selective cyclooxygenase-2 (COX-2) inhibitor SC-236 (4 mg/kg) on the simultaneous responsiveness of spinal wide-dynamic range (WDR) neurons and single motor units (SMUs) from gastrocnemius soleus muscles to mechanical stimuli (pressure and pinch) and repeated suprathreshold (1.5xT, the intensity threshold) electrical stimuli with different frequencies (3 Hz, 20 Hz) under normal conditions and bee venom (BV, 0.2 mg/50 microl)-induced inflammation and central sensitization. During normal conditions, the responses of SMUs, but not WDR neurons, to mechanical and repeated electrical stimuli (3 Hz, wind-up) were depressed by systemic administration of SC-236 as well as its vehicle (100% dimethyl sulfoxide (DMSO)). The after-discharges of both the WDR neurons and the simultaneously recorded SMUs after electrical stimuli with 20 Hz were markedly depressed only by SC-236, indicating that the mechanisms underlying the generation of the C-fiber mediated late responses and the after-discharges may be different. The enhanced responsiveness of both WDR neurons and SMUs to mechanical pressure stimuli (allodynia) and pinch stimuli (hyperalgesia) in the BV experiments was apparently depressed by SC-236, but not its vehicle. For electrical stimulation, the enhanced late responses and after-discharges, but not early responses, of both the WDR neurons and the simultaneously recorded SMUs were markedly depressed only by SC-236. This indicates that different central pharmacological mechanisms underlie the generation of these enhanced early, late responses, and after-discharges during BV-induced inflammation. The data suggest that the COX-2 inhibitor SC-236 apparently depress the activities of both spinal cord dorsal horn neuron and spinal withdrawal reflex during BV-induced sensitization, indicating that COX-2 plays an important role in the maintenance of central sensitization.
本研究的目的是检测选择性环氧化酶-2（COX-2）抑制剂SC-236（4毫克/千克）对正常条件下以及蜂毒（BV，0.2毫克/50微升）诱导的炎症和中枢敏化状态下，脊髓广动力范围（WDR）神经元和比目鱼肌腓肠肌单运动单位（SMU）对机械刺激（压力和捏压）以及不同频率（3赫兹、20赫兹）的重复阈上（1.5倍阈强度）电刺激的同步反应性的影响。在正常条件下，全身给予SC-236及其溶剂（100%二甲基亚砜（DMSO））会抑制SMU对机械和重复电刺激（3赫兹，wind-up）的反应，但不影响WDR神经元。仅SC-236能显著抑制20赫兹电刺激后WDR神经元和同时记录的SMU的后放电，这表明C纤维介导的迟发反应和后放电产生的机制可能不同。在BV实验中，SC-236能明显抑制WDR神经元和SMU对机械压力刺激（痛觉过敏）和捏压刺激（痛觉超敏）增强的反应性，而其溶剂则无此作用。对于电刺激，仅SC-236能显著抑制WDR神经元和同时记录的SMU增强的迟发反应和后放电，而不影响早发反应。这表明在BV诱导的炎症过程中，这些增强的早发、迟发反应和后放电的产生存在不同的中枢药理机制。数据表明，COX-2抑制剂SC-236在BV诱导的敏化过程中明显抑制脊髓背角神经元的活动和脊髓退缩反射，这表明COX-2在中枢敏化的维持中起重要作用。
