King's College London

Research portal

Evoked and ongoing pain-like behaviours in a rat model of paclitaxel-induced peripheral neuropathy

Research output: Contribution to journalArticle

Original languageEnglish
Article number8217613
Number of pages11
JournalPain Research and Management
Volume2018
Early online date3 Jun 2018
DOIs
Accepted/In press3 May 2018
E-pub ahead of print3 Jun 2018
Published2018

Documents

King's Authors

Abstract

Paclitaxel-induced neuropathic pain is a major dose-limiting side-effect of paclitaxel therapy. This study characterises a variety of rat behavioural responses induced by intermittent administration of clinically-formulated paclitaxel. 2mg/kg paclitaxel or equivalent vehicle was administered intraperitoneally on days 0, 2, 4 & 6 to adult male Sprague-Dawley rats. Evoked pain-like behaviours were assessed with von Frey filaments, acetone, or radiant heat application to plantar hind paws to ascertain mechanical, cold, or heat sensitivity, respectively. Motor coordination was evaluated using an accelerating Rotarod. Ongoing pain-like behaviour was assessed via spontaneous burrowing and nocturnal wheel running. Mechanical and cold hypersensitivity developed after a delayed onset, peaked approximately day 28 and persisted for several months. Heat sensitivity and motor coordination were unaltered in paclitaxel-treated rats. Spontaneous burrowing behaviour and nocturnal wheel running were significantly impaired at day 28, but not day 7, indicating ongoing pain-like behaviour, rather than acute drug toxicity. This study comprehensively characterises a rat model of paclitaxel-induced peripheral neuropathy providing the first evidence for ongoing pain-like behaviour, which occurs in parallel to maximal mechanical/cold hypersensitivity. We hope this new data improves the face validity of rat models to better reflect patient-reported pain symptoms, aiding translation of new treatments to the clinic.

Download statistics

No data available

View graph of relations

© 2020 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454