Vafaei Abbas Ali, Safakhah Hossein Ali, Jafari Simin, Tavasoli Azin, Rashidy-Pour Ali, Ghanbari Ali, Seyedinia Seyed Ali, Tarahomi Parnia
Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran.
Department of Physiology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
J Exp Pharmacol. 2020 Apr 28;12:97-106. doi: 10.2147/JEP.S250738. eCollection 2020.
Neuropathic pain involves injury or alteration of the normal sensory and modulatory nervous systems to produce a set of symptoms that are often difficult to treat. Previous study indicates that crocin has anti-inflammatory properties that may be mediated by the neurotransmitter system. In this study, we determine if there is an interaction between crocin and the cannabinoid system on chronic constriction injury (CCI)-induced neuropathic pain in male rats.
In this experimental study, adult male Wistar rats (220-250 g) were used. CCI was induced by setting four loose ligatures around the sciatic nerve. In part 1, after nerve lesion, vehicle, crocin (60 mg/kg) or Win 55-212-2 (0.1 mg/kg) as an agonist and AM 251 (0.1 mg/kg) as an antagonist of cannabinoid receptors were injected intraperitoneally daily in separate groups for 2 weeks. In part 2, two weeks after nerve lesion, vehicle (5 µL), crocin (6 µg/5 µL), Win 55-212-2 (0.1 µg/5 µL), AM 251 (0.1 µg/5 µL) were administered intracerebroventricularly (ICV) in separate groups. Mechanical allodynia and thermal hyperalgesia were measured using Von Frey filaments and plantar test device, respectively, at day 14. Data were analyzed by two-way ANOVA and Sidak's multiple comparisons post-test.
Results indicated that centrally administered crocin significantly decreased thermal hyperalgesia and mechanical allodynia. Also, peripheral injection of crocin significantly decreased mechanical allodynia but not thermal hyperalgesia. Central or peripheral administration of Win 55-212-2 or AM 251 modulates the analgesic effect of crocin significantly.
Our findings showed that crocin has significant analgesic effects that are probably mediated by an endocannabinoid mechanism.
神经性疼痛涉及正常感觉和调节神经系统的损伤或改变，从而产生一系列往往难以治疗的症状。先前的研究表明，藏红花素具有抗炎特性，可能由神经递质系统介导。在本研究中，我们确定藏红花素与大麻素系统之间是否存在相互作用，对雄性大鼠慢性压迫损伤（CCI）诱导的神经性疼痛产生影响。
在本实验研究中，使用成年雄性Wistar大鼠（220 - 250克）。通过在坐骨神经周围设置四个宽松结扎线诱导CCI。在第1部分中，神经损伤后，分别在不同组中每天腹腔注射赋形剂、藏红花素（60毫克/千克）或作为激动剂的Win 55-212-2（0.1毫克/千克）以及作为大麻素受体拮抗剂的AM 251（0.1毫克/千克），持续2周。在第2部分中，神经损伤两周后，分别在不同组中脑室内（ICV）注射赋形剂（5微升）、藏红花素（6微克/5微升）、Win 55-212-2（0.1微克/5微升）、AM 251（0.1微克/5微升）。在第14天分别使用von Frey细丝和足底测试装置测量机械性异常性疼痛和热痛觉过敏。数据通过双向方差分析和Sidak多重比较后检验进行分析。
结果表明，脑室内注射藏红花素可显著降低热痛觉过敏和机械性异常性疼痛。此外，外周注射藏红花素可显著降低机械性异常性疼痛，但不能降低热痛觉过敏。脑室内或外周注射Win 55-212-2或AM 251可显著调节藏红花素的镇痛作用。
我们的研究结果表明，藏红花素具有显著的镇痛作用，可能由内源性大麻素机制介导。
