Reduced GABAergic transmission in the ventrobasal thalamus contributes to thermal hyperalgesia in chronic inflammatory pain.
The ventrobasal (VB) thalamus is innervated by GABAergic afferents from the thalamic reticular nucleus (TRN) and participates in nociception. But how the TRN-VB pathway regulates pain is not fully understood. In the present study, we reported decreased extracellular GABA levels in the VB of rats with CFA-induced chronic inflammatory pain, measured by microdialysis with HPLC analysis. In vitro whole-cell patch-clamp recording showed decreased amplitudes of tonic currents, increased frequencies of mIPSCs, and increased paired-pulse ratios in thalamic slices from chronic inflammatory rats (7 days). Microinjection of the GABAAR agonist muscimol and optogenetic activation of the TRN-VB pathway relieved thermal hyperalgesia in chronic inflammatory pain. By contrast, microinjecting the extrasynaptic GABAAR agonist THIP or selective knockout of synaptic GABAAR γ2 subunits aggravated thermal hyperalgesia in the chronic stage of inflammatory pain. Our findings indicate that reduced GABAergic transmission in the VB contributes to thermal hyperalgesia in chronic inflammatory pain, which could be a synaptic target for pharmacotherapy.
Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, 100191, P.R. China.|Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, P.R. China.
Chan
C
Zhang
Research Center for Medicine and Biology, Zunyi Medical University, Zunyi, 563000, P.R. China.
Rong-Xiang
RX
Chen
Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, 100191, P.R. China.
Yu
Y
Zhang
Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, 430071, P.R. China.
Jie
J
Wang
Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, 100191, P.R. China.
Feng-Yu
FY
Liu
Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, 100191, P.R. China.
Jie
J
Cai
Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, 100191, P.R. China.
Fei-Fei
FF
Liao
Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, 430071, P.R. China.
Fu-Qiang
FQ
Xu
Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, 100191, P.R. China. mingyi@bjmu.edu.cn.
Ming
M
Yi
Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, 100191, P.R. China. ywan@hsc.pku.edu.cn.|Key Laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Beijing, 100191, P.R. China. ywan@hsc.pku.edu.cn.
You
Y
Wan
D000818:Animals; D059350:Chronic Pain / Q000150:complications / Q000503:physiopathology*; D005110:Extracellular Space / Q000378:metabolism; D005620:Freund's Adjuvant; D059330:GABAergic Neurons / Q000502:physiology*; D055786:Gene Knockout Techniques; D006930:Hyperalgesia / Q000150:complications / Q000503:physiopathology*; D007249:Inflammation / Q000150:complications / Q000503:physiopathology*; D007555:Isoxazoles / Q000494:pharmacology; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D062308:Optogenetics; D018408:Patch-Clamp Techniques; D021122:Protein Subunits / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D009435:Synaptic Transmission; D013788:Thalamus / Q000473:pathology / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D007555:Isoxazoles; D021122:Protein Subunits; D011963:Receptors, GABA-A; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D005620:Freund's Adjuvant; C015542:gaboxadol