Acute PAR2 activation reduces GABAergic inhibition in the spinal dorsal horn.
We investigated the mechanism underlying inhibition of spinal dorsal horn GABAergic neurotransmission to elucidate the role of protease-activated receptor-2 (PAR2). Initially, we confirmed that PAR2 agonist SL-NH(2) applied intrathecally produced mechanical hyperalgesia. Then we performed patch-clamp experiments in substantia gelatinosa neurons of spinal cord slice, and found that spontaneous inhibitory post-synaptic currents (sIPSCs) were significantly decreased in both frequency and amplitude when neurons were incubated with PAR2 agonist SL-NH(2) for a brief time period (2 min). The GABA-mediated currents were significantly reduced, and there was no impact on glycine-mediated currents during this SL-NH(2) treatment. These results suggest that PAR2 activation enhanced the pain response, potentially via inhibition of dorsal horn GABAergic neurotransmission.
Department of Anesthesiology, Eastern Hepatobiliary Surgical Hospital, Second Military Medical University, Shanghai, China.
Zhangxiang
Z
Huang
Kunming
K
Tao
Hai
H
Zhu
Xuerong
X
Miao
Zhengmeng
Z
Wang
Weifeng
W
Yu
Zhijie
Z
Lu
D000818:Animals; D015536:Down-Regulation / Q000502:physiology; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D008297:Male; D009433:Neural Inhibition / Q000502:physiology*; D010147:Pain Measurement / Q000379:methods; D020671:Posterior Horn Cells / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D044464:Receptor, PAR-2 / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D044464:Receptor, PAR-2; D005680:gamma-Aminobutyric Acid