Ge, Meng-Meng, Chen, Shu-Ping, Zhou, Ya-Qun, Li, Zheng, Tian, Xue-Bi, Gao, Feng, Manyande, Anne ORCID: https://orcid.org/0000-0002-8257-0722, Tian, Yu-Ke and Yang, Hui (2019) The therapeutic potential of GABA in neuron-glia interactions of cancer-induced bone pain. European Journal of Pharmacology, 858 (172475). ISSN 0014-2999

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Abstract

Abstract: The development of effective therapeutics for cancer-induced bone pain (CIBP) remains a tremendous challenge owing to its unclear mechanisms. Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system. Emerging studies have shown that disinhibition in the spinal cord dorsal horn may account for the development of chronic pain. However, the role of GABA in the development of CIBP remains elusive. In addition, accumulating evidence has shown that neuroglial cells in the peripheral nervous system, especially astrocytes and microglial cells, play an important role in the maintenance of CIBP. In this study, we investigated the expression of GABA and Gamma-aminobutyric acid transporter-1 (GAT-1), a transporter of GABA. Our results demonstrate that GABA was decreased in CIBP rats as expected. However, the expression of glutamic acid decarboxylase (GAD) 65 was up-regulated on day 21 after surgery, while the expression of glutamic acid decarboxylase (GAD) 67 remained unchanged after surgery. We also found that the expression of GAT-1 was up-regulated mainly in the astrocytes of the spinal cord. Moreover, we evaluated the analgesic effect of exogenous GABA and the GAT-1 inhibitor. Intrathecal administration of exogenous GABA and NO-711(a GAT-1 selective inhibitor) significantly reversed CIBP-induced mechanical allodynia in a dose-dependent manner. These results firstly show that neuron-glia interactions, especially on the GABAnergic pathway, contribute to the development of CIBP. In conclusion, exogenous GABA and GAT-1 inhibitor might be alternative therapeutic strategies for the treatment of CIBP.
Keywords: Cancer-induced bone pain; Gamma-Aminobutyric acid; Glutamic acid decarboxylases; GABA transporters; NO-711; Astrocyte

Item Type:	Article
Identifier:	10.1016/j.ejphar.2019.172475
Keywords:	Cancer-induced bone pain, Gamma-aminobutyric acid, Glutamic acid decarboxylases, GABA transporters, NO-711, Astrocyte
Subjects:	Medicine and health > Clinical medicine Medicine and health
Depositing User:	Anne Manyande
Date Deposited:	24 Jun 2019 14:21
Last Modified:	04 Nov 2024 11:53
URI:	https://repository.uwl.ac.uk/id/eprint/6176

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