.png){kind=icon}
.png){kind=icon}
Return
An NLRP3 inflammasome inhibitor evoked dose-dependent anti-allodynia in the hindpaws of a rat model of chemotherapy-induced peripheral neuropathy
.png){kind=icon}
OA
AI
L
M
O
A
K
M
DOI：10.1007/s10787-026-02360-w.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
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.
Keywords:
Chemotherapy induced peripheral neuropathy (CIPN)
Cisplatin
Mechanical allodynia
Neuropathic pain
MCC950
NLRP3 inflammasome inhibitor
Pregabalin
Journal
IF:
5.3
Papers:
744
Citations:
6.6K
Organization
Cited Papers