Korean J Physiol Pharmacol.  2018 Jul;22(4):419-425. 10.4196/kjpp.2018.22.4.419.

The effect of µ-opioid receptor activation on GABAergic neurons in the spinal dorsal horn

Affiliations
  • 1Department of Physiology, Seoul National University College of Medicine, Seoul 03080, Korea. sangjkim@snu.ac.kr
  • 2Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.
  • 3Neuroscience Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
  • 4Department of Physiology, College of Korean Medicine, Gachon University, Seongnam 13120, Korea.

Abstract

The superficial dorsal horn of the spinal cord plays an important role in pain transmission and opioid activity. Several studies have demonstrated that opioids modulate pain transmission, and the activation of µ-opioid receptors (MORs) by opioids contributes to analgesic effects in the spinal cord. However, the effect of the activation of MORs on GABAergic interneurons and the contribution to the analgesic effect are much less clear. In this study, using transgenic mice, which allow the identification of GABAergic interneurons, we investigated how the activation of MORs affects the excitability of GABAergic interneurons and synaptic transmission between primary nociceptive afferent and GABAergic interneurons. We found that a selective µ-opioid agonist, [D-Ala², NMe-Phe⁴, Gly-ol]-enkephanlin (DAMGO), induced an outward current mediated by K⁺ channels in GABAergic interneurons. In addition, DAMGO reduced the amplitude of evoked excitatory postsynaptic currents (EPSCs) of GABAergic interneurons which receive monosynaptic inputs from primary nociceptive C fibers. Taken together, we found that DAMGO reduced the excitability of GABAergic interneurons and synaptic transmission between primary nociceptive C fibers and GABAergic interneurons. These results suggest one possibility that suppression of GABAergic interneurons by DMAGO may reduce the inhibition on secondary GABAergic interneurons, which increase the inhibition of the secondary GABAergic interneurons to excitatory neurons in the spinal dorsal horn. In this circumstance, the sum of excitation of the entire spinal network will control the pain transmission.

Keyword

DAMGO; GABAergic interneurons; Opioid; Pain; Substantia gelatinosa
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