Abstract
Background: Paclitaxel-induced peripheral neuropathy is a common and limiting side effect of an approved and effective chemotherapeutic agent. The cause of this nociception is still unknown. Methods: To uncover the mechanism involved in paclitaxel-induced pain, we developed a Drosophila thermal nociceptive model to show the effects of paclitaxel exposure on third instar larvae. Results: We found that paclitaxel increases heat nociception in a dose-dependent manner, and at the highest doses also obstructs dendritic repulsion cues. Conclusions: Our simple system can be applied to identify regulators of chemotherapy-induced pain and may help to eliminate pain-related side-effects of chemotherapy.
Highlights
Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect of many effective cancer treatments (Burton et al, 2007), and can have a lasting impact on the quality of life of cancer survivors (Hausheer et al, 2006 and Shimozuma et al, 2012)
Based on previous studies for toxicity (Bhattacharya et al, 2012; Cunha et al, 2001), we selected paclitaxel doses below the lethal limit (Figure 1A), and tested larval nociception using a heat probe set to a low intensity noxious heat (42°C; Figure 1B), which is mildly nociceptive to fly larvae (Babcock et al, 2009)
Here we report a simple, high-throughput genetically tractable system to dissect the mechanisms of CIPN in Drosophila
Summary
Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect of many effective cancer treatments (Burton et al, 2007), and can have a lasting impact on the quality of life of cancer survivors (Hausheer et al, 2006 and Shimozuma et al, 2012). Patients treated with paclitaxel experience side effects as early as one to three days following treatment (Lipton et al, 1989; Reyes-Gibby et al, 2009). Paclitaxel-induced peripheral neuropathy is a common and limiting side effect of an approved and effective chemotherapeutic agent. The cause of this nociception is still unknown. Keywords Drosophila, fruit fly, paclitaxel, nociception, pain, CIPN version 2 (revision) Conclusions: Our simple system can be applied to identify regulators of chemotherapy-induced pain and may help to eliminate pain-related side-effects of chemotherapy.
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