2026
Inflammopharmacology 2026 Aug 10. doi: 10.1007/s10787-026-02360-w. Online ahead of print.
An NLRP3 inflammasome inhibitor evoked dose-dependent anti-allodynia in the hindpaws of a rat model of chemotherapy-induced peripheral neuropathy
Faculty of Health, Medicine and Behavioural Sciences, Centre for Integrated Preclinical Drug Development, School of Biomedical Sciences, The University of Queensland, St Lucia Campus, Brisbane, QLD, 4072, Australia. Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
Service type: Stock strains
Abstract
Patients receiving chemotherapy for cancer treatment may develop chemotherapy-induced peripheral neuropathy (CIPN), a type of neuropathic (nerve) pain that is often difficult to treat. First-line analgesic/adjuvant agents recommended for the treatment of neuropathic pain often lack efficacy and/or evoke dose-limiting side-effects in patients with CIPN. Hence, there is a large unmet medical need for novel, well-tolerated analgesics for improving the relief of CIPN. As NLRP3 inflammasome activation is implicated in the pathobiology of CIPN, our aim was to assess the pain relief efficacy of a small molecule NLRP3 inflammasome inhibitor (MCC950), for the relief of CIPN in a rat model. Sprague-Dawley rats received four doses of cisplatin at once-weekly intervals. Temporal development of mechanical allodynia was documented in the bilateral hindpaws using von Frey filaments over a 4-week period after the first cisplatin dose. Rats with fully developed mechanical allodynia in the hindpaws received single oral doses of MCC950 (10-300 mg/kg), pregabalin (30 mg/kg) or vehicle. Hindpaw withdrawal thresholds were assessed pre-dose and at multiple times over a 4 h post-dosing period to produce PWT versus time curves. Single doses of MCC950 evoked dose-dependent anti-allodynia in the hindpaws, with the peak effect observed at 2-3 h post-dose. The mean effective dose 50% (ED50; 95% confidence intervals) of MCC950 was 56.2 mg/kg (21.8-150.7 mg/kg). On a molar basis, oral pregabalin was ~ 20% more potent than MCC950 in this model. In conclusion, NLRP3 inflammasome inhibitors are worthy of further investigation as novel treatments for CIPN.
View Publication
