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The effect of intrathecal administration of glial activation inhibitors on dorsal horn BDNF overexpression and hind paw mechanical allodynia in spinal nerve ligated rats.
J Neural Transm (Vienna). 2012 Mar; 119(3):329-36.JN

Abstract

Recent studies have suggested that activated glia in the spinal cord may play a vital role at different times during spinal nerve ligation (SNL)-induced neuropathic pain; therefore, glial activation inhibitors have been used as effective painkillers. Brain-derived neurotrophic factor (BDNF) is also known to be a powerful pain modulator, but it remains unclear how it contributes to the glial activation inhibitor-based treatment. This study revealed the following results: (1) intrathecal administration of minocycline (a microglial activation inhibitor) could prevent mechanical allodynia during the initiation of SNL-induced neuropathic pain, and its action was associated with the elimination of BDNF overexpression in the dorsal horn; (2) the spinal injection of fluorocitrate (an astrocytic activation inhibitor) but not minocycline could reverse mechanical allodynia during the maintenance phase of SNL-induced pain, and its action was also related to a decrease in BDNF overexpression in the dorsal horn; and (3) treatment with TrkB/Fc (a BDNF-sequestering protein) had a similar effect during both the early development and maintenance periods. These results led to the following conclusions: (1) elevated BDNF expression in the dorsal horn was required to develop and maintain neuropathic pain; (2) minocycline could only prevent mechanical allodynia in the early stages, possibly by inhibiting BDNF release from microglia; and (3) fluorocitrate could reverse existing mechanical allodynia, and its action was associated with the inhibition of BDNF upregulation induced by astrocytic activation.

Authors+Show Affiliations

Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, People's Republic of China.No affiliation info availableNo affiliation info availableNo 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

21901501

Citation

Zhang, Xin, et al. "The Effect of Intrathecal Administration of Glial Activation Inhibitors On Dorsal Horn BDNF Overexpression and Hind Paw Mechanical Allodynia in Spinal Nerve Ligated Rats." Journal of Neural Transmission (Vienna, Austria : 1996), vol. 119, no. 3, 2012, pp. 329-36.
Zhang X, Xu Y, Wang J, et al. The effect of intrathecal administration of glial activation inhibitors on dorsal horn BDNF overexpression and hind paw mechanical allodynia in spinal nerve ligated rats. J Neural Transm (Vienna). 2012;119(3):329-36.
Zhang, X., Xu, Y., Wang, J., Zhou, Q., Pu, S., Jiang, W., & Du, D. (2012). The effect of intrathecal administration of glial activation inhibitors on dorsal horn BDNF overexpression and hind paw mechanical allodynia in spinal nerve ligated rats. Journal of Neural Transmission (Vienna, Austria : 1996), 119(3), 329-36. https://doi.org/10.1007/s00702-011-0713-7
Zhang X, et al. The Effect of Intrathecal Administration of Glial Activation Inhibitors On Dorsal Horn BDNF Overexpression and Hind Paw Mechanical Allodynia in Spinal Nerve Ligated Rats. J Neural Transm (Vienna). 2012;119(3):329-36. PubMed PMID: 21901501.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of intrathecal administration of glial activation inhibitors on dorsal horn BDNF overexpression and hind paw mechanical allodynia in spinal nerve ligated rats. AU - Zhang,Xin, AU - Xu,Yongming, AU - Wang,Jing, AU - Zhou,Quanhong, AU - Pu,Shaofeng, AU - Jiang,Wei, AU - Du,Dongping, Y1 - 2011/09/07/ PY - 2011/06/05/received PY - 2011/08/23/accepted PY - 2011/9/9/entrez PY - 2011/9/9/pubmed PY - 2012/7/24/medline SP - 329 EP - 36 JF - Journal of neural transmission (Vienna, Austria : 1996) JO - J Neural Transm (Vienna) VL - 119 IS - 3 N2 - Recent studies have suggested that activated glia in the spinal cord may play a vital role at different times during spinal nerve ligation (SNL)-induced neuropathic pain; therefore, glial activation inhibitors have been used as effective painkillers. Brain-derived neurotrophic factor (BDNF) is also known to be a powerful pain modulator, but it remains unclear how it contributes to the glial activation inhibitor-based treatment. This study revealed the following results: (1) intrathecal administration of minocycline (a microglial activation inhibitor) could prevent mechanical allodynia during the initiation of SNL-induced neuropathic pain, and its action was associated with the elimination of BDNF overexpression in the dorsal horn; (2) the spinal injection of fluorocitrate (an astrocytic activation inhibitor) but not minocycline could reverse mechanical allodynia during the maintenance phase of SNL-induced pain, and its action was also related to a decrease in BDNF overexpression in the dorsal horn; and (3) treatment with TrkB/Fc (a BDNF-sequestering protein) had a similar effect during both the early development and maintenance periods. These results led to the following conclusions: (1) elevated BDNF expression in the dorsal horn was required to develop and maintain neuropathic pain; (2) minocycline could only prevent mechanical allodynia in the early stages, possibly by inhibiting BDNF release from microglia; and (3) fluorocitrate could reverse existing mechanical allodynia, and its action was associated with the inhibition of BDNF upregulation induced by astrocytic activation. SN - 1435-1463 UR - https://www.unboundmedicine.com/medline/citation/21901501/The_effect_of_intrathecal_administration_of_glial_activation_inhibitors_on_dorsal_horn_BDNF_overexpression_and_hind_paw_mechanical_allodynia_in_spinal_nerve_ligated_rats_ L2 - https://doi.org/10.1007/s00702-011-0713-7 DB - PRIME DP - Unbound Medicine ER -