Rock Erin M, Limebeer Cheryl L, Parker Linda A
Department of Psychology, University of Guelph, Guelph, ON, N1G 2W1, Canada.
Exp Brain Res. 2014 Aug;232(8):2511-34. doi: 10.1007/s00221-014-3942-9. Epub 2014 May 4.
Cancer patients undergoing chemotherapy continue to experience the debilitating side effect of nausea associated with their treatment. Although acute and delayed vomiting have become well managed with the advent of the 5-hydroxytryptamine-3 antagonists, such as ondansetron, and the neurokinin-1 receptor antagonists (such as aprepitant), nausea is still a relatively unmanaged adverse side effect of chemotherapy treatment. When nausea and vomiting are not properly managed, patients are at a greater risk of developing anticipatory nausea (AN)--a conditional association between chemotherapy-related treatment cues, such as the clinic environment, and the subsequent nausea experienced. Once it develops, AN is refractive to pharmacological treatment with classic antiemetics. Currently, non-specific antianxiety drugs (benzodiazepines) are prescribed; however, their sedating side effects are undesirable. Here, we review the animal models of AN that have been developed. These preclinical models have aided researchers in the evaluation of potentially efficacious pharmacological treatments for AN. Accumulating evidence using animal models demonstrates that cannabinoid compounds effectively reduce AN, without producing sedation. These results highlight the need for human clinical trials evaluating the efficacy of these compounds.
接受化疗的癌症患者在治疗过程中仍会经历令人虚弱的恶心副作用。尽管随着5-羟色胺-3拮抗剂(如昂丹司琼)和神经激肽-1受体拮抗剂(如阿瑞匹坦)的出现,急性和延迟性呕吐已得到很好的控制,但恶心仍然是化疗治疗中相对难以控制的不良副作用。当恶心和呕吐得不到妥善处理时,患者出现预期性恶心(AN)的风险更大——这是一种化疗相关治疗线索(如临床环境)与随后出现的恶心之间的条件性关联。一旦发生,AN对经典止吐药的药物治疗具有抗性。目前,会开非特异性抗焦虑药物(苯二氮䓬类);然而,它们的镇静副作用是不理想的。在此,我们综述已开发的AN动物模型。这些临床前模型有助于研究人员评估针对AN的潜在有效药物治疗方法。使用动物模型积累的证据表明,大麻素化合物可有效减轻AN,且不会产生镇静作用。这些结果凸显了进行人体临床试验以评估这些化合物疗效的必要性。