Evoked and Ongoing Pain-Like Behaviours in a Rat Model of Paclitaxel-Induced Peripheral Neuropathy

Authors
LA Gri_ths, NA Duggett, AL Pitcher, SJL Flatter

Lab
Wolfson Centre for Age-Related Diseases, King’s College London, London, UK

Journal
Pain Research and Management

Abstract
Paclitaxel-inducedneuropathicpainisamajordose-limitingsidee_ectofpaclitaxeltherapy.Thisstudycharacterisesavarietyof rat behavioural responses induced by intermittent administration of clinically formulated paclitaxel. 2mg/kg paclitaxel or equivalentvehiclewasadministeredintraperitoneallyondays0,2,4,and6toadultmaleSprague-Dawleyrats.Evokedpain-like behaviours were assessed with von Frey _laments, 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 apparatus. Ongoing pain-like behaviour was assessed via spontaneous burrowing and nocturnal wheel running. Mechanical and cold hypersensitivity developed after a delayed onset, peaked approximately on day 28, and persisted for several months. Heat sensitivity and motor coordination were unaltered in paclitaxel-treated rats. Spontaneous burrowing behaviour and nocturnal wheelrunningweresigni_cantlyimpairedonday28,butnotonday7,indicatingongoingpain-likebehaviour,ratherthanacute drug toxicity. This study comprehensively characterises a rat model of paclitaxel-induced peripheral neuropathy, providing the _rstevidenceforongoingpain-likebehaviour,whichoccursinparallelwithmaximalmechanical/coldhypersensitivity.Wehope that this new data improve the face validity of rat models to better re_ect patient-reported pain symptoms, aiding translation of new treatments to the clinic.

BIOSEB Instruments Used:
Spontaneous activity wheels (BIO-ACTIVW-M)