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Article
Oxaliplatin Neurotoxicity of Sensory Transduction in Rat Proprioceptors
Journal of Neurophysiology
  • Katie L. Bullinger
  • Paul Nardelli, Wright State University - Main Campus
  • Qingbo Wang, Wright State University - Main Campus
  • Mark M. Rich, Wright State University - Main Campus
  • Timothy C. Cope, Wright State University - Main Campus
Document Type
Article
Publication Date
8-1-2011
Abstract
Neurotoxic effects of oxaliplatin chemotherapy, including proprioceptive impairments, are debilitating and dose limiting. Here, we sought to determine whether oxaliplatin interrupts normal proprioceptive feedback by impairing sensory transduction of muscle length and force by neurons that are not damaged by dying-back neuropathy. Oxaliplatin was administered over four weeks to rats in doses that produced systemic changes, e.g., decreased platelets and stunted weight gain, but no significant abnormality in the terminal ends of primary muscle spindle sensory neurons. The absence of neuropathy enabled the determination of whether oxaliplatin caused functional deficits in sensory encoding without the confounding issue of axon death. Rats were anesthetized, and action potentials encoding muscle stretch and contraction were recorded intra-axonally from dorsal roots. In striking contrast with normal proprioceptors, those from oxaliplatin-treated rats typically failed to sustain firing during static muscle stretch. The ability of spindle afferents to sustain and centrally conduct trains of action potentials in response to rapidly repeated transient stimuli, i.e., vibration, demonstrated functional competence of the parent axons. These data provide the first evidence that oxaliplatin causes persistent and selective deficits in sensory transduction that are not due to axon degeneration. Our findings raise the possibility that even those axons that do not degenerate after oxaliplatin treatment may have functional deficits that worsen outcome.
DOI
10.1152/jn.00083.2011
Citation Information
Katie L. Bullinger, Paul Nardelli, Qingbo Wang, Mark M. Rich, et al.. "Oxaliplatin Neurotoxicity of Sensory Transduction in Rat Proprioceptors" Journal of Neurophysiology Vol. 106 Iss. 2 (2011) p. 704 - 709 ISSN: 1522-1598
Available at: http://works.bepress.com/timothy_cope/58/