Institute of Experimental and Clinical Pharmacology and Toxicology, FAU Erlangen-Nuremberg, Fahrstr. 17, 91054 Erlangen, Germany.
Toxicon. 2013 Nov;74:44-55. doi: 10.1016/j.toxicon.2013.07.019. Epub 2013 Aug 3.
Crotoxin, the main neurotoxic component of the venom of South American rattlesnake (Crotalus durissus terrificus), is reported to have potent antinociceptive activity. Several authors have shown mainly in behavioral pain models that crotoxin induces antinociceptive effects, supposed to be mediated by actions on the central nervous system. The antinociceptive effects of crotoxin (45 μg/kg ip) in rats were verified in this study by increased response latencies in a Hargreaves test and tail flick test. In addition, it was demonstrated that crotoxin does not lead to motor impairments during a rotarod test and open field test. The main objective, carried out by blood oxygen level dependent functional Magnetic Resonance Imaging (BOLD fMRI) in anesthetized rats, was to determine which specific brain structures are involved in these antinociceptive effects. Moreover, potential antihyperalgesic effects were investigated by inducing a local hyperalgesia on the left hind paw. Therefore, antinociceptive effects (right paw) and antihyperalgesic effects (left paw) of crotoxin were able to be differentiated. As a result, crotoxin exhibited dominant antihyperalgesic but also antinociceptive effects during pain stimulation. Reductions of BOLD signal already occurred in brain input structures but were most prominent in primary and secondary somatosensory cortices. In conclusion, BOLD fMRI in anesthetized rats proved to be a helpful tool in toxinology, particularly in unraveled mechanisms of modulating nociception in the central nervous system by (potential) analgesics like crotoxin.
响尾蛇毒素是南美的响尾蛇（Crotalus durissus terrificus）毒液的主要神经毒性成分，据报道具有很强的镇痛活性。几位作者主要在行为疼痛模型中表明，响尾蛇毒素诱导镇痛作用，推测是通过对中枢神经系统的作用介导的。本研究通过增加 Hargreaves 试验和尾巴拍打试验中的反应潜伏期来验证响尾蛇毒素（45μg/kg ip）在大鼠中的镇痛作用。此外，还证明响尾蛇毒素在旋转棒试验和旷场试验中不会导致运动障碍。在麻醉大鼠中进行的基于血氧水平依赖的功能磁共振成像（BOLD fMRI）的主要目的是确定哪些特定的脑结构参与这些镇痛作用。此外，通过在左后爪上引起局部痛觉过敏来研究潜在的抗痛觉过敏作用。因此，可以区分响尾蛇毒素的镇痛作用（右爪）和抗痛觉过敏作用（左爪）。结果表明，在疼痛刺激期间，响尾蛇毒素表现出主要的抗痛觉过敏作用，但也有镇痛作用。BOLD 信号的减少已经发生在大脑输入结构中，但在初级和次级体感皮层中最为明显。总之，麻醉大鼠的 BOLD fMRI 被证明是毒理学中的一种有用工具，特别是在阐明（潜在）镇痛药如响尾蛇毒素在中枢神经系统中调节痛觉的机制方面。
