Involvement of spinal glutamate transporter-1 in the development of mechanical allodynia and hyperalgesia associated with type 2 diabetes

Jinshan Shi,^1,* Ke Jiang,^2,* Zhaoduan Li,<sup>3

1</sup>Department of Anesthesiology, Guizhou Provincial People’s Hospital, ²Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, ³Department of Anesthesiology, Tianjin Nankai Hospital, Tianjin, People’s Republic of China

*These authors contributed equally to this work
 
Abstract: Little is known about the effects of the development of type 2 diabetes on glutamate homeostasis in the spinal cord. Therefore, we quantified the extracellular levels of glutamate in the spinal cord of Zucker diabetic fatty (ZDF) rats using in vivo microdialysis. In addition, protein levels of glutamate transporter-1 (GLT-1) in the spinal cord of ZDF rats were measured using Western blot. Finally, the effects of repeated intrathecal injections of ceftriaxone, which was previously shown to enhance GLT-1 expression, on the development of mechanical allodynia and hyperalgesia as well as on basal extracellular level of glutamate and the expression of GLT-1 in the spinal cord of ZDF rats were evaluated. It was found that ZDF rats developed mechanical hyperalgesia and allodynia, which were associated with increased basal extracellular levels of glutamate and attenuated levels of GLT-1 expression in the spinal cord, particularly in the dorsal horn. Furthermore, repeated intrathecal administrations of ceftriaxone dose-dependently prevented the development of mechanical hyperalgesia and allodynia in ZDF rats, which were correlated with enhanced GLT-1 expression without altering the basal glutamate levels in the spinal cord of ZDF rats. Overall, the results suggested that impaired glutamate reuptake in the spinal cord may contribute to the development of neuropathic pains in type 2 diabetes.

Keywords: diabetes, peripheral neuropathy, spinal cord, Zucker diabetic fatty rats, glutamate, glutamate transporter-1