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Microtubule disorientation and axonal swelling in unmyelinated sensory axons during vincristine-induced painful neuropathy in rat.
J Comp Neurol. 1998 Jun 15; 395(4):481-92.JC

Abstract

Neuropathic pain accompanies peripheral nerve injury following a variety of insults including metabolic disorders, traumatic injury, and exposure to neurotoxins such as vincristine and taxol. Vincristine, a microtubule depolymerizing drug, produces a peripheral neuropathy in humans that is accompanied by painful paresthesias and dysesthesias (Sandler et al., [1969] Neurology 19:367-374; Holland et al. [1973] Cancer Res. 33:1258-1264). The recent development of an animal model of vincristine-induced neuropathy provides an opportunity to investigate mechanisms underlying this form of neuropathic pain. Systemic vincristine (100 microg/kg) produces hyperalgesia to mechanical stimuli during the second week of administration, which persists for more than a week (Aley et al. [1996] Neuroscience 73:259-265). To test the hypothesis that changes in microtubule structure in nociceptive sensory neurons accompany vincristine-induced hyperalgesia, we analyzed unmyelinated axons in saphenous nerves of vincristine-treated rats. This study constitutes the first quantitative ultrastructural analysis of the cytoskeleton of unmyelinated axons in peripheral nerve during neuropathic hyperalgesia. There was no evidence of unmyelinated fiber loss or a decrease in the number of microtubules per axons. There was, however, a significant decrease in microtubule density in unmyelinated axons from vincristine-treated rats. This decrease in microtubule density was due to a significant increase in the cross-sectional area of unmyelinated axons, suggesting swelling of axons. In addition, vincristine-treated axons had significantly fewer microtubules cut in cross-section and significantly more tangentially oriented microtubules per axon compared to controls. These results suggest that vincristine causes disorganization of the axonal microtubule cytoskeleton, as well as an increase in the caliber of unmyelinated sensory axons.

Authors+Show Affiliations

Program in Neuroscience, University of California, San Francisco 94143-0736, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

9619501

Citation

Tanner, K D., et al. "Microtubule Disorientation and Axonal Swelling in Unmyelinated Sensory Axons During Vincristine-induced Painful Neuropathy in Rat." The Journal of Comparative Neurology, vol. 395, no. 4, 1998, pp. 481-92.
Tanner KD, Levine JD, Topp KS. Microtubule disorientation and axonal swelling in unmyelinated sensory axons during vincristine-induced painful neuropathy in rat. J Comp Neurol. 1998;395(4):481-92.
Tanner, K. D., Levine, J. D., & Topp, K. S. (1998). Microtubule disorientation and axonal swelling in unmyelinated sensory axons during vincristine-induced painful neuropathy in rat. The Journal of Comparative Neurology, 395(4), 481-92.
Tanner KD, Levine JD, Topp KS. Microtubule Disorientation and Axonal Swelling in Unmyelinated Sensory Axons During Vincristine-induced Painful Neuropathy in Rat. J Comp Neurol. 1998 Jun 15;395(4):481-92. PubMed PMID: 9619501.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Microtubule disorientation and axonal swelling in unmyelinated sensory axons during vincristine-induced painful neuropathy in rat. AU - Tanner,K D, AU - Levine,J D, AU - Topp,K S, PY - 1998/6/10/pubmed PY - 2000/6/20/medline PY - 1998/6/10/entrez SP - 481 EP - 92 JF - The Journal of comparative neurology JO - J Comp Neurol VL - 395 IS - 4 N2 - Neuropathic pain accompanies peripheral nerve injury following a variety of insults including metabolic disorders, traumatic injury, and exposure to neurotoxins such as vincristine and taxol. Vincristine, a microtubule depolymerizing drug, produces a peripheral neuropathy in humans that is accompanied by painful paresthesias and dysesthesias (Sandler et al., [1969] Neurology 19:367-374; Holland et al. [1973] Cancer Res. 33:1258-1264). The recent development of an animal model of vincristine-induced neuropathy provides an opportunity to investigate mechanisms underlying this form of neuropathic pain. Systemic vincristine (100 microg/kg) produces hyperalgesia to mechanical stimuli during the second week of administration, which persists for more than a week (Aley et al. [1996] Neuroscience 73:259-265). To test the hypothesis that changes in microtubule structure in nociceptive sensory neurons accompany vincristine-induced hyperalgesia, we analyzed unmyelinated axons in saphenous nerves of vincristine-treated rats. This study constitutes the first quantitative ultrastructural analysis of the cytoskeleton of unmyelinated axons in peripheral nerve during neuropathic hyperalgesia. There was no evidence of unmyelinated fiber loss or a decrease in the number of microtubules per axons. There was, however, a significant decrease in microtubule density in unmyelinated axons from vincristine-treated rats. This decrease in microtubule density was due to a significant increase in the cross-sectional area of unmyelinated axons, suggesting swelling of axons. In addition, vincristine-treated axons had significantly fewer microtubules cut in cross-section and significantly more tangentially oriented microtubules per axon compared to controls. These results suggest that vincristine causes disorganization of the axonal microtubule cytoskeleton, as well as an increase in the caliber of unmyelinated sensory axons. SN - 0021-9967 UR - https://www.unboundmedicine.com/medline/citation/9619501/Microtubule_disorientation_and_axonal_swelling_in_unmyelinated_sensory_axons_during_vincristine_induced_painful_neuropathy_in_rat_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0021-9967&date=1998&volume=395&issue=4&spage=481 DB - PRIME DP - Unbound Medicine ER -