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Up-regulation of tumor necrosis factor-alpha in spinal cord contributes to vincristine-induced mechanical allodynia in mice.
Neurosci Lett. 2008 Nov 14; 445(2):140-3.NL

Abstract

Chronic treatment with vincristine (VCR) causes mechanical allodynia as an adverse effect. We previously reported that peripheral macrophage-derived interleukin-6 played a critical role in VCR-induced allodynia. However, the involvement of glial cell activation and central sensitization in VCR-induced allodynia is still unclear. In this study, we focused on tumor necrosis factor-alpha (TNF-alpha) in spinal cord, and investigated the role of TNF-alpha in VCR-induced allodynia in mice. VCR (0.1mg/kg, i.p.) was administered to mice once per day for 7 days. The expression of TNF-alpha mRNA and the protein in spinal cord was evaluated by quantitative real-time PCR and immunohistochemistry, respectively. In VCR-treated mice, TNF-alpha mRNA gradually increased and was significantly up-regulated on day 7. As measured by immunohistochemistry, microglia and astrocytes were activated in the spinal dorsal horn on day 7 of VCR administration. The immunoreactivity of TNF-alpha was co-localized in some of the activated microglia and astrocytes. In behavioral analysis, a neutralizing antibody of TNF-alpha, which was injected intrathecally on days 0, 3, and 6, significantly attenuated VCR-induced mechanical allodynia on days 4 and 7. These results suggest that VCR treatments elicited the activation of glial cells in spinal cord, and up-regulated TNF-alpha in these cells may play an important role in VCR-induced mechanical allodynia.

Authors+Show Affiliations

Department of Pharmacology, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Wakayama 641-0012, Japan.No 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

18790011

Citation

Kiguchi, Norikazu, et al. "Up-regulation of Tumor Necrosis Factor-alpha in Spinal Cord Contributes to Vincristine-induced Mechanical Allodynia in Mice." Neuroscience Letters, vol. 445, no. 2, 2008, pp. 140-3.
Kiguchi N, Maeda T, Kobayashi Y, et al. Up-regulation of tumor necrosis factor-alpha in spinal cord contributes to vincristine-induced mechanical allodynia in mice. Neurosci Lett. 2008;445(2):140-3.
Kiguchi, N., Maeda, T., Kobayashi, Y., & Kishioka, S. (2008). Up-regulation of tumor necrosis factor-alpha in spinal cord contributes to vincristine-induced mechanical allodynia in mice. Neuroscience Letters, 445(2), 140-3. https://doi.org/10.1016/j.neulet.2008.09.009
Kiguchi N, et al. Up-regulation of Tumor Necrosis Factor-alpha in Spinal Cord Contributes to Vincristine-induced Mechanical Allodynia in Mice. Neurosci Lett. 2008 Nov 14;445(2):140-3. PubMed PMID: 18790011.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Up-regulation of tumor necrosis factor-alpha in spinal cord contributes to vincristine-induced mechanical allodynia in mice. AU - Kiguchi,Norikazu, AU - Maeda,Takehiko, AU - Kobayashi,Yuka, AU - Kishioka,Shiroh, Y1 - 2008/09/07/ PY - 2008/08/08/received PY - 2008/08/22/revised PY - 2008/09/02/accepted PY - 2008/9/16/pubmed PY - 2009/4/15/medline PY - 2008/9/16/entrez SP - 140 EP - 3 JF - Neuroscience letters JO - Neurosci Lett VL - 445 IS - 2 N2 - Chronic treatment with vincristine (VCR) causes mechanical allodynia as an adverse effect. We previously reported that peripheral macrophage-derived interleukin-6 played a critical role in VCR-induced allodynia. However, the involvement of glial cell activation and central sensitization in VCR-induced allodynia is still unclear. In this study, we focused on tumor necrosis factor-alpha (TNF-alpha) in spinal cord, and investigated the role of TNF-alpha in VCR-induced allodynia in mice. VCR (0.1mg/kg, i.p.) was administered to mice once per day for 7 days. The expression of TNF-alpha mRNA and the protein in spinal cord was evaluated by quantitative real-time PCR and immunohistochemistry, respectively. In VCR-treated mice, TNF-alpha mRNA gradually increased and was significantly up-regulated on day 7. As measured by immunohistochemistry, microglia and astrocytes were activated in the spinal dorsal horn on day 7 of VCR administration. The immunoreactivity of TNF-alpha was co-localized in some of the activated microglia and astrocytes. In behavioral analysis, a neutralizing antibody of TNF-alpha, which was injected intrathecally on days 0, 3, and 6, significantly attenuated VCR-induced mechanical allodynia on days 4 and 7. These results suggest that VCR treatments elicited the activation of glial cells in spinal cord, and up-regulated TNF-alpha in these cells may play an important role in VCR-induced mechanical allodynia. SN - 0304-3940 UR - https://www.unboundmedicine.com/medline/citation/18790011/Up_regulation_of_tumor_necrosis_factor_alpha_in_spinal_cord_contributes_to_vincristine_induced_mechanical_allodynia_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(08)01233-0 DB - PRIME DP - Unbound Medicine ER -