Exploring the incidence and variability of oxaliplatin-induced neuropathic pain symptoms in colorectal cancer patients, comparative in vivo / in vitro modelling of oxaliplatin/ 56MESS(IV) as an alternative cancer treatment, and minocycline administration as a prophylactic agent for chemotherapy-induced neuropathic pain

Abstract

Oxaliplatin is commonly used for the treatment of advanced and recurrent colorectal cancer (CRC). However, oxaliplatin-induced neuropathic pain remains a challenge for the healthcare systems worldwide. In chapter II, the incidence and impact of acute oxaliplatin-induced neuropathic pain on chemotherapy treatment in colorectal cancer patients in the first cycle from the published research literature was explored. In chapter III, the variability of oxaliplatin-induced neuropathic pain symptoms from the Southwestern Sydney Local Health District Hospitals (SWLHDHs) database of patients who received oxaliplatin based chemotherapy treatment (2011-2015) and the implications for the management of colorectal cancer patients was assessed. In chapter IV, it was explored whether oxaliplatin can induce behavioural hypersensitivity in healthy rats using the dosing regimen that mimics the standard clinical protocols (oxaliplatin 2.5 mg/kg i.p every two weeks). In chapter V, the effects of oxaliplatin and 56MESS(IV) on the viability, PI staining (cell death) and activation (nitrite production) of RAW264.7 (macrophages) and N11 (microglia) cell lines were explored in vitro. In summary, oxaliplatin-induced neuropathic pain remains a big problem as it affects treatment compliance in quarter of CRC patients during cycle 1 and as neuropathic pain symptoms oscillate across cycles for individual patients. This warrants further detailed patient-by-patient analysis of pain symptoms in future clinical trials. Additionally, the in vivo and in vitro data showed that minocycline pre-treatment has a potential to ameliorate oxaliplatin and 56MESS(IV) induced production of pro-inflammatory chemical mediators such as nitrite in vitro cell lines, which may be relevant to in vivo models of chemotherapy-induced neuropathic pain. However, oxaliplatin-induced neuropathic pain is more likely multifactorial and research should be continued on the mechanisms of neuropathy and potential therapeutic drugs.

Date of Award	2021
Original language	English