期刊
MOLECULAR NEUROBIOLOGY
卷 59, 期 10, 页码 6049-6061出版社
SPRINGER
DOI: 10.1007/s12035-022-02955-8
关键词
Chronic neuropathic pain; Cognitive impairment; GABA(A)Rs-alpha 5; Inhibitory synaptic transmission
资金
- National Natural Science Foundation of China [82071196]
- Jiangsu Commission of Health [z201949]
- Basic Research Grant of Southeast University
The alpha 5-containing GABA(A) receptors (GABA(A)Rs-alpha 5) play a crucial role in chronic neuropathic pain-induced cognitive impairment by weakening inhibitory synaptic transmission. Inhibition of GABA(A)Rs-alpha 5 can rescue weakened inhibitory synaptic transmission and cognitive impairment caused by chronic neuropathic pain.
Chronic neuropathic pain often leads to cognitive impairment, but the exact mechanism remains unclear. Gammaaminobutyric acid A receptors (GABA(A)Rs) are the major inhibitory receptors in the brain, of which the alpha 5-containing GABA(A)Rs (GABA(A)Rs-alpha 5) are implicated in a range of neuropsychiatric disorders with cognitive deficits. However, whether GABA(A)Rs-alpha 5 are involved in chronic neuropathic pain-related cognitive impairment remains unknown. In this study, the rats with chronic neuropathic pain induced by right sciatic nerve ligation injury (SNI) exhibited cognitive impairment with declined spontaneous alternation in Y-maze test and discrimination index in novel object recognition test. The GABA(A)Rs-alpha 5 expressing on parvalbumin and somatostatin interneurons increased remarkably in hippocampus, resulting in decreased mean frequency of spontaneous inhibitory postsynaptic currents in hippocampal pyramidal neurons. Significantly, antagonizing the GABA(A)Rs-alpha 5 by L655708 rescued weakened inhibitory synaptic transmission and cognitive impairment induced by chronic neuropathic pain. Taken together, these data suggest that the GABA(A)Rs-alpha 5 play a crucial role in chronic neuropathic pain-induced cognitive impairment by weakening inhibitory synaptic transmission, which may provide insights into the pharmacologic treatment of chronic neuropathic pain-related cognitive impairment.
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