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Spinal astrocytic activation contributes to mechanical allodynia in a mouse model of type 2 diabetes.
Brain Res. 2011 Jan 12; 1368:324-35.BR

Abstract

Diabetic neuropathic pain (DNP) plays a major role in decreased life quality of type 2 diabetes patients, however, the molecular mechanisms underlying DNP remain unclear. Emerging research implicates the participation of spinal glial cells in some neuropathic pain models. However, it remains unknown whether spinal glial cells are activated under type 2 diabetic conditions and whether they contribute to diabetes-induced neuropathic pain. In the present study, using a db/db type 2 diabetes mouse model that displayed obvious mechanical allodynia, we found that spinal astrocyte but not microglia was dramatically activated. The mechanical allodynia was significantly attenuated by intrathecally administrated l-α-aminoadipate (astrocytic specific inhibitor) whereas minocycline (microglial specific inhibitor) did not have any effect on mechanical allodynia, which indicated that spinal astrocytic activation contributed to allodynia in db/db mice. Further study aimed to identify the detailed mechanism of astrocyte-induced allodynia in db/db mice. Results showed that spinal activated astrocytes dramatically increased interleukin (IL)-1β expression which may induce N-methyl-D-aspartic acid receptor (NMDAR) phosphorylation in spinal dorsal horn neurons to enhance pain transmission. Together, these results suggest that spinal activated astrocytes may be a crucial component of mechanical allodynia in type 2 diabetes and "Astrocyte-IL-1β-NMDAR-Neuron" pathway may be the detailed mechanism of astrocyte-induced allodynia. Thus, inhibiting astrocytic activation in the spinal dorsal horn may represent a novel therapeutic strategy for treating DNP.

Authors+Show Affiliations

Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

20971097

Citation

Liao, Yong-Hui, et al. "Spinal Astrocytic Activation Contributes to Mechanical Allodynia in a Mouse Model of Type 2 Diabetes." Brain Research, vol. 1368, 2011, pp. 324-35.
Liao YH, Zhang GH, Jia D, et al. Spinal astrocytic activation contributes to mechanical allodynia in a mouse model of type 2 diabetes. Brain Res. 2011;1368:324-35.
Liao, Y. H., Zhang, G. H., Jia, D., Wang, P., Qian, N. S., He, F., Zeng, X. T., He, Y., Yang, Y. L., Cao, D. Y., Zhang, Y., Wang, D. S., Tao, K. S., Gao, C. J., & Dou, K. F. (2011). Spinal astrocytic activation contributes to mechanical allodynia in a mouse model of type 2 diabetes. Brain Research, 1368, 324-35. https://doi.org/10.1016/j.brainres.2010.10.044
Liao YH, et al. Spinal Astrocytic Activation Contributes to Mechanical Allodynia in a Mouse Model of Type 2 Diabetes. Brain Res. 2011 Jan 12;1368:324-35. PubMed PMID: 20971097.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Spinal astrocytic activation contributes to mechanical allodynia in a mouse model of type 2 diabetes. AU - Liao,Yong-Hui, AU - Zhang,Gui-He, AU - Jia,Dong, AU - Wang,Peng, AU - Qian,Nian-Song, AU - He,Fei, AU - Zeng,Xiang-Tian, AU - He,Yong, AU - Yang,Yan-Ling, AU - Cao,Da-Yong, AU - Zhang,Yi, AU - Wang,De-Sheng, AU - Tao,Kai-Shan, AU - Gao,Chang-Jun, AU - Dou,Ke-Feng, Y1 - 2010/11/12/ PY - 2010/09/02/received PY - 2010/10/10/revised PY - 2010/10/14/accepted PY - 2010/10/26/entrez PY - 2010/10/26/pubmed PY - 2011/7/1/medline SP - 324 EP - 35 JF - Brain research JO - Brain Res VL - 1368 N2 - Diabetic neuropathic pain (DNP) plays a major role in decreased life quality of type 2 diabetes patients, however, the molecular mechanisms underlying DNP remain unclear. Emerging research implicates the participation of spinal glial cells in some neuropathic pain models. However, it remains unknown whether spinal glial cells are activated under type 2 diabetic conditions and whether they contribute to diabetes-induced neuropathic pain. In the present study, using a db/db type 2 diabetes mouse model that displayed obvious mechanical allodynia, we found that spinal astrocyte but not microglia was dramatically activated. The mechanical allodynia was significantly attenuated by intrathecally administrated l-α-aminoadipate (astrocytic specific inhibitor) whereas minocycline (microglial specific inhibitor) did not have any effect on mechanical allodynia, which indicated that spinal astrocytic activation contributed to allodynia in db/db mice. Further study aimed to identify the detailed mechanism of astrocyte-induced allodynia in db/db mice. Results showed that spinal activated astrocytes dramatically increased interleukin (IL)-1β expression which may induce N-methyl-D-aspartic acid receptor (NMDAR) phosphorylation in spinal dorsal horn neurons to enhance pain transmission. Together, these results suggest that spinal activated astrocytes may be a crucial component of mechanical allodynia in type 2 diabetes and "Astrocyte-IL-1β-NMDAR-Neuron" pathway may be the detailed mechanism of astrocyte-induced allodynia. Thus, inhibiting astrocytic activation in the spinal dorsal horn may represent a novel therapeutic strategy for treating DNP. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/20971097/Spinal_astrocytic_activation_contributes_to_mechanical_allodynia_in_a_mouse_model_of_type_2_diabetes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(10)02313-9 DB - PRIME DP - Unbound Medicine ER -