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Damage to the cytoskeleton of large diameter sensory neurons and myelinated axons in vincristine-induced painful peripheral neuropathy in the rat.
J Comp Neurol. 2000 Sep 04; 424(4):563-76.JC

Abstract

Vincristine, along with other antimitotic chemotherapeutic drugs, produces a peripheral neuropathy in humans that is accompanied by painful paresthesias, dysesthesias, and occasionally hypoesthesia, and by hyporeflexia (Holland et al. [1973] Cancer Res. 33:1258-1264; McLeod and Penny [1969] J Neurol Neurosurg Psychiatry 32:297-304; Postma et al. [1993] J Neurooncol. 15:23-27; Sandler et al. [1969] Neurology 19:367-374). Systemic administration of vincristine causes swelling of unmyelinated axons and disorientation of axonal microtubules (Tanner et al. [1998a1998a] J Comp Neurol. 395:481-492) at a time when it also produces allodynia and mechanical hyperalgesia (Aley et al. [1996] Neuroscience 73:259-265; Authier et al. [1999] Neuroreport 10:965-968) and enhanced responsiveness in C-fibers in the rat (Tanner et al. [1998b] J Neurosci. 18:6480-6491). Because slowing of A-fiber conduction velocities had also been demonstrated (Tanner et al. [1998b] J Neurosci. 18:6480-6491), and mechanical hyperalgesia can occur secondary to damage to large diameter sensory afferents (Basbaum et al. [1991] Can J Physiol Pharmacol. 69:647-651; Coggeshall et al. [1993] Pain 52:233-242; Woolf and Mannion [1999] Lancet 353:1959-1964), we sought to determine whether vincristine also induced ultrastructural changes in myelinated A-fibers. Moreover, since systemic treatment with vincristine did not cause profound microtubule depolymerization in the unmyelinated axons of the peripheral nerve, we hypothesized that the drug's effects may be more extensive in the cell body, because in the spinal ganglion, the blood-nerve barrier is less restrictive. We used quantitative ultrastructural methods to analyze the microtubule cytoskeleton in myelinated axons in the mid-shaft of the saphenous nerve and in the sensory ganglion cells. Vincristine induced swelling of the whole nerve and an increase in the cross-sectional areas of myelinated axons but no loss of myelinated axons. There was a significant decrease in axonal microtubules, as well as microtubule disorganization, in myelinated fibers from vincristine-treated rats. In the spinal ganglion, vincristine induced swelling of large diameter sensory neurons and a build-up of neurofilaments in the cell bodies and proximal axons, suggestive of impaired anterograde axonal transport.

Authors+Show Affiliations

Department of Physical Therapy and Rehabilitation Science, University of California, San Francisco, California 94143-0736, USA. Kstopp@itsa.ucsf.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10931481

Citation

Topp, K S., et al. "Damage to the Cytoskeleton of Large Diameter Sensory Neurons and Myelinated Axons in Vincristine-induced Painful Peripheral Neuropathy in the Rat." The Journal of Comparative Neurology, vol. 424, no. 4, 2000, pp. 563-76.
Topp KS, Tanner KD, Levine JD. Damage to the cytoskeleton of large diameter sensory neurons and myelinated axons in vincristine-induced painful peripheral neuropathy in the rat. J Comp Neurol. 2000;424(4):563-76.
Topp, K. S., Tanner, K. D., & Levine, J. D. (2000). Damage to the cytoskeleton of large diameter sensory neurons and myelinated axons in vincristine-induced painful peripheral neuropathy in the rat. The Journal of Comparative Neurology, 424(4), 563-76.
Topp KS, Tanner KD, Levine JD. Damage to the Cytoskeleton of Large Diameter Sensory Neurons and Myelinated Axons in Vincristine-induced Painful Peripheral Neuropathy in the Rat. J Comp Neurol. 2000 Sep 4;424(4):563-76. PubMed PMID: 10931481.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Damage to the cytoskeleton of large diameter sensory neurons and myelinated axons in vincristine-induced painful peripheral neuropathy in the rat. AU - Topp,K S, AU - Tanner,K D, AU - Levine,J D, PY - 2000/8/10/pubmed PY - 2000/9/9/medline PY - 2000/8/10/entrez SP - 563 EP - 76 JF - The Journal of comparative neurology JO - J Comp Neurol VL - 424 IS - 4 N2 - Vincristine, along with other antimitotic chemotherapeutic drugs, produces a peripheral neuropathy in humans that is accompanied by painful paresthesias, dysesthesias, and occasionally hypoesthesia, and by hyporeflexia (Holland et al. [1973] Cancer Res. 33:1258-1264; McLeod and Penny [1969] J Neurol Neurosurg Psychiatry 32:297-304; Postma et al. [1993] J Neurooncol. 15:23-27; Sandler et al. [1969] Neurology 19:367-374). Systemic administration of vincristine causes swelling of unmyelinated axons and disorientation of axonal microtubules (Tanner et al. [1998a1998a] J Comp Neurol. 395:481-492) at a time when it also produces allodynia and mechanical hyperalgesia (Aley et al. [1996] Neuroscience 73:259-265; Authier et al. [1999] Neuroreport 10:965-968) and enhanced responsiveness in C-fibers in the rat (Tanner et al. [1998b] J Neurosci. 18:6480-6491). Because slowing of A-fiber conduction velocities had also been demonstrated (Tanner et al. [1998b] J Neurosci. 18:6480-6491), and mechanical hyperalgesia can occur secondary to damage to large diameter sensory afferents (Basbaum et al. [1991] Can J Physiol Pharmacol. 69:647-651; Coggeshall et al. [1993] Pain 52:233-242; Woolf and Mannion [1999] Lancet 353:1959-1964), we sought to determine whether vincristine also induced ultrastructural changes in myelinated A-fibers. Moreover, since systemic treatment with vincristine did not cause profound microtubule depolymerization in the unmyelinated axons of the peripheral nerve, we hypothesized that the drug's effects may be more extensive in the cell body, because in the spinal ganglion, the blood-nerve barrier is less restrictive. We used quantitative ultrastructural methods to analyze the microtubule cytoskeleton in myelinated axons in the mid-shaft of the saphenous nerve and in the sensory ganglion cells. Vincristine induced swelling of the whole nerve and an increase in the cross-sectional areas of myelinated axons but no loss of myelinated axons. There was a significant decrease in axonal microtubules, as well as microtubule disorganization, in myelinated fibers from vincristine-treated rats. In the spinal ganglion, vincristine induced swelling of large diameter sensory neurons and a build-up of neurofilaments in the cell bodies and proximal axons, suggestive of impaired anterograde axonal transport. SN - 0021-9967 UR - https://www.unboundmedicine.com/medline/citation/10931481/Damage_to_the_cytoskeleton_of_large_diameter_sensory_neurons_and_myelinated_axons_in_vincristine_induced_painful_peripheral_neuropathy_in_the_rat_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0021-9967&date=2000&volume=424&issue=4&spage=563 DB - PRIME DP - Unbound Medicine ER -