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Inhibition of paclitaxel-induced A-fiber hypersensitization by gabapentin.
J Pharmacol Exp Ther. 2006 Aug; 318(2):735-40.JP

Abstract

Paclitaxel (Taxol) is a widely used chemotherapeutic agent in the treatment of several tumors. However, its use is often associated with the generation of peripheral neuropathic pain expressed as mechanical allodynia and thermal hyperalgesia. The molecular mechanism behind this debilitating side effect is obscure, and efficient drugs for its prevention are required. We sought to clarify the cellular changes in the involved nociceptor types underlying paclitaxel-induced neuropathic pain and to test for an alleviating effect of gabapentin treatment in a murine model of paclitaxel-induced neuropathic pain. We found that a single treatment with paclitaxel (4 mg/kg i.p.) led to a decrease in both thermal and mechanical nociceptive thresholds as well as a reduction in the thresholds for 250-Hz (A delta-fiber) and 2000 Hz (A beta-fiber) but not 5-Hz (C-fiber) sine wave electrical stimuli-induced paw withdrawal. The paclitaxel-induced neuropathic pain was completely abrogated by gabapentin (30 mg/kg i.p.) treatment. Furthermore, we found that mRNA and protein levels of the voltage-gated calcium channel (alpha 2)delta-1 subunit (Ca(alpha 2)delta-1), one of the putative targets for gabapentin, was up-regulated in dorsal root ganglions (DRGs), as well as increased expression of Ca(alpha 2)delta-1 protein in medium/large-sized DRG neurons by immunohistochemistry, following paclitaxel treatment. This suggests that paclitaxel induces A-fiber-specific hypersensitization, which may contribute to the functional mechanical allodynia and hyperalgesia, and that gabapentin could be a potential therapeutic agent for paclitaxel-induced neuropathic pain.

Authors+Show Affiliations

Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16687474

Citation

Matsumoto, Misaki, et al. "Inhibition of Paclitaxel-induced A-fiber Hypersensitization By Gabapentin." The Journal of Pharmacology and Experimental Therapeutics, vol. 318, no. 2, 2006, pp. 735-40.
Matsumoto M, Inoue M, Hald A, et al. Inhibition of paclitaxel-induced A-fiber hypersensitization by gabapentin. J Pharmacol Exp Ther. 2006;318(2):735-40.
Matsumoto, M., Inoue, M., Hald, A., Xie, W., & Ueda, H. (2006). Inhibition of paclitaxel-induced A-fiber hypersensitization by gabapentin. The Journal of Pharmacology and Experimental Therapeutics, 318(2), 735-40.
Matsumoto M, et al. Inhibition of Paclitaxel-induced A-fiber Hypersensitization By Gabapentin. J Pharmacol Exp Ther. 2006;318(2):735-40. PubMed PMID: 16687474.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of paclitaxel-induced A-fiber hypersensitization by gabapentin. AU - Matsumoto,Misaki, AU - Inoue,Makoto, AU - Hald,Andreas, AU - Xie,Weijiao, AU - Ueda,Hiroshi, Y1 - 2006/05/10/ PY - 2006/5/12/pubmed PY - 2006/9/1/medline PY - 2006/5/12/entrez SP - 735 EP - 40 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 318 IS - 2 N2 - Paclitaxel (Taxol) is a widely used chemotherapeutic agent in the treatment of several tumors. However, its use is often associated with the generation of peripheral neuropathic pain expressed as mechanical allodynia and thermal hyperalgesia. The molecular mechanism behind this debilitating side effect is obscure, and efficient drugs for its prevention are required. We sought to clarify the cellular changes in the involved nociceptor types underlying paclitaxel-induced neuropathic pain and to test for an alleviating effect of gabapentin treatment in a murine model of paclitaxel-induced neuropathic pain. We found that a single treatment with paclitaxel (4 mg/kg i.p.) led to a decrease in both thermal and mechanical nociceptive thresholds as well as a reduction in the thresholds for 250-Hz (A delta-fiber) and 2000 Hz (A beta-fiber) but not 5-Hz (C-fiber) sine wave electrical stimuli-induced paw withdrawal. The paclitaxel-induced neuropathic pain was completely abrogated by gabapentin (30 mg/kg i.p.) treatment. Furthermore, we found that mRNA and protein levels of the voltage-gated calcium channel (alpha 2)delta-1 subunit (Ca(alpha 2)delta-1), one of the putative targets for gabapentin, was up-regulated in dorsal root ganglions (DRGs), as well as increased expression of Ca(alpha 2)delta-1 protein in medium/large-sized DRG neurons by immunohistochemistry, following paclitaxel treatment. This suggests that paclitaxel induces A-fiber-specific hypersensitization, which may contribute to the functional mechanical allodynia and hyperalgesia, and that gabapentin could be a potential therapeutic agent for paclitaxel-induced neuropathic pain. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/16687474/Inhibition_of_paclitaxel_induced_A_fiber_hypersensitization_by_gabapentin_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=16687474 DB - PRIME DP - Unbound Medicine ER -