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Open Access Highly Accessed Open Badges Research article

GABAergic synaptic response and its opioidergic modulation in periaqueductal gray neurons of rats with neuropathic pain

Eu-Teum Hahm12, Younghoon Kim1, Jong-Ju Lee3 and Young-Wuk Cho1*

  • * Corresponding author: Young-Wuk Cho

  • † Equal contributors

Author Affiliations

1 Department of Physiology, Biomedical Science Institute, Kyung Hee University School of Medicine, Seoul 130-701, South Korea

2 Department of Physiology and Biophysics, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USA

3 Department of Dental Pharmacology, School of Dentistry, Kyungpook National University, Daegu 700-412, South Korea

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BMC Neuroscience 2011, 12:41  doi:10.1186/1471-2202-12-41

Published: 12 May 2011



Neuropathic pain is a chronic and intractable symptom associated with nerve injury. The periaqueductal gray (PAG) is important in the endogenous pain control system and is the main site of the opioidergic analgesia. To investigate whether neuropathic pain affects the endogenous pain control system, we examined the effect of neuropathic pain induced by sacral nerve transection on presynaptic GABA release, the kinetics of postsynaptic GABA-activated Cl- currents, and the modulatory effect of μ-opioid receptor (MOR) activation in mechanically isolated PAG neurons with functioning synaptic boutons.


In normal rats, MOR activation inhibited the frequency of GABAergic miniature inhibitory postsynaptic currents (mIPSCs) to 81.3% of the control without any alteration in their amplitude. In neuropathic rats, the inhibition of mIPSC frequency by MOR activation was 82.4%. The frequency of GABAergic mIPSCs in neuropathic rats was 151.8% of normal rats without any difference in the mIPSC amplitude. Analysis of mIPSC kinetics showed that the fast decay time constant and synaptic charge transfer of mIPSCs in neuropathic rats were 76.0% and 73.2% of normal rats, respectively.


These results indicate that although the inhibitory effect of MOR activation on presynaptic GABA release is similar in both neuropathic and normal rats, neuropathic pain may inhibit endogenous analgesia in the PAG through an increase in presynaptic GABA release.

Neuropathic pain; Endogenous pain control system; Opioid analgesia; GABAergic synaptic transmission; Periaqueductal gray