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.
Liao
Yong-Hui
YH
Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, PR China.
Zhang
Gui-He
GH
Jia
Dong
D
Wang
Peng
P
Qian
Nian-Song
NS
He
Fei
F
Zeng
Xiang-Tian
XT
He
Yong
Y
Yang
Yan-Ling
YL
Cao
Da-Yong
DY
Zhang
Yi
Y
Wang
De-Sheng
DS
Tao
Kai-Shan
KS
Gao
Chang-Jun
CJ
Dou
Ke-Feng
KF
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