Effects of paclitaxel on the viscoelastic properties of mouse sensory nerves

Rishi S. Gupta, Daniel Berrellez, Neha Chhugani, Carlos Luna Lopez, Amir Maldonado, Sameer B. Shah*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Paclitaxel is an effective and widely used chemotherapeutic, but also causes debilitating peripheral sensory neuropathy. Due to its influence on microtubule stability, we and others have hypothesized that paclitaxel alters neuromechanical properties. A prior study suggested that paclitaxel increases the tensile moduli of rat sensory nerves. However, the effects of paclitaxel on tissue level viscoelasticity have not been tested. In this study, sural branches of C57BL/6J mouse sciatic nerves were bilaterally excised. One nerve was treated with Ringer's solution containing paclitaxel, and the contralateral nerve with Ringer's alone. Nerves were then subject to a passive loading protocol in which peak stress, relaxed stress, and stress-relaxation dynamics were monitored at increasing strain. Elastic and tangent tensile moduli were calculated from both peak and relaxed stress-strain curves as well as failure stress were significantly elevated in paclitaxel-treated nerves compared to controls. Double-exponential fits (with τm and τn indicating fast and slow time constants, respectively) were successfully applied to model stress-relaxation. Though no significant differences in the τm and τn were found between groups, paclitaxel treatment significantly increased the variability of τm, suggesting heterogeneous effects on nerve biomechanical properties. Our data establish that paclitaxel effects at the cellular level influence tensile viscoelastic properties of nerves at the tissue level. These results have implications for understanding biomechanical influences on the progression and physical rehabilitation of paclitaxel-induced neuropathy.

Original languageEnglish
Article number110125
JournalJournal of Biomechanics
Volume115
DOIs
StatePublished - 22 Jan 2021

Bibliographical note

Funding Information:
We acknowledge funding from the UCSD Department of Orthopaedic Surgery. D. B. acknowledges an international travel grant from Conacyt-Mexico. We are grateful to the Biophysical Society for a Networking award that supported this collaboration. We gratefully appreciate animal handling assistance from Ms. Stephanie Adachi and Ms. Elisabeth Orozco.

Publisher Copyright:
© 2020

Keywords

  • Biomechanics
  • Microtubule
  • Paclitaxel-induced neuropathy
  • Peripheral nerve
  • Viscoelasticity

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