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Abstract
Despite the large amount of human and experimental studies no effective (prophylactic) treatment exists for chemotherapy induced peripheral neuropathy (CIPN), a disabling side effect of many cancer treatments. One of the underlying reasons for this could be that often the preclinical animal models used are not the best representation of the clinical situation. We therefore present a systematic summary and comparison of all animal models currently described in literature for CIPN focusing on stimulus evoked pain-like behaviour and neurophysiological alterations in nerve function (650 included papers, and a comparison of 183 models), that resulted in a clear overview of the most effective and robust CIPN models using an administration route used in clinical practice. Using our three-step approach (step 1: efficacy; step; 2 robustness and step 3: mimicking the clinical situation) we show that all mice CIPN models treated with either paclitaxel or cisplatin using an administration route used in clinical practice seem suitable models. Three specific models using paclitaxel or cisplatin that stand out are 1) C57BL/6 female mice receiving paclitaxel and 2) CD1 male mice receiving paclitaxel and 3) C57BL/6 male mice receiving cisplatin. This overview may help scientists selecting suitable CIPN models for their research. We hypothesize that by using effective and robust animal models that mimic the clinical situation as much as possible, the translational value of preclinical study results with respect to the potential of identifying promising treatments for CIPN in the future, will prove. The methodology described in this paper, aimed at comparing animal models, is novel and can be used by scientist in other research fields as well.
Highlights
We conducted a comprehensive summary and comparison of all animal models currently described in literature for chemotherapy induced peripheral neuropathy (CIPN), that resulted in a clear overview of all effective and robust models for CIPN focusing on stimulus evoked pain-like behaviour and neurophysiological alterations in nerve function with an administration route used in clinical practice
Using our three-step approach we show in this systematic review that all mice CIPN models treated with either paclitaxel or cisplatin using an administration route used in clinical practice seem suitable models
In this systematic review we show evidence that mice CIPN models treated with either paclitaxel or cisplatin using an administration route used in clinical practice seem suitable models to study CIPN
Summary
One of the most common reported symptoms derived from cancer treatment is chemotherapy induced peripheral neuropathy (CIPN), which is caused by differential damage to peripheral nervous system depending on the administered neurotoxic antineoplastic agent, such as taxanes, platinum compounds, vinca alkaloids, epothilones, protease inhibitors and thalidomide [5, 6]. It mainly presents as a dose-dependent sensory length-dependent neuropathy with symptoms including numbness, paresthesias, loss of proprioception and hyperalgesia; less often patients will present with motor weakness and autonomic changes [7, 8]. Despite the large amount of human and experimental studies, until now no effective prophylactic treatment exists [15,16,17], treatment of CIPN related pain remains difficult [5, 15, 16, 18] and reduces quality of life of cancer patients and survivors [19]
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