Spinal astrocytic activation contributes to mechanical allodynia in a mouse model of type 2 diabetes.
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.
Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, PR China.
Yong-Hui
YH
Liao
Gui-He
GH
Zhang
Dong
D
Jia
Peng
P
Wang
Nian-Song
NS
Qian
Fei
F
He
Xiang-Tian
XT
Zeng
Yong
Y
He
Yan-Ling
YL
Yang
Da-Yong
DY
Cao
Yi
Y
Zhang
De-Sheng
DS
Wang
Kai-Shan
KS
Tao
Chang-Jun
CJ
Gao
Ke-Feng
KF
Dou
D015074:2-Aminoadipic Acid / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000209:etiology / Q000378:metabolism*; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D007278:Injections, Spinal; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008911:Minocycline / Q000008:administration & dosage / Q000494:pharmacology; D010147:Pain Measurement / Q000379:methods; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D016896:Treatment Outcome
D018691:Excitatory Amino Acid Antagonists; D053583:Interleukin-1beta; D015074:2-Aminoadipic Acid; D008911:Minocycline