NDLI: Mechanism Underlying the Analgesic Effect Exerted by Endomorphin-1 in the rat Ventrolateral Periaqueductal Gray

Content Provider	Springer Nature Link
Author	Chen, Tao Li, Jing Feng, Ban Hui, Rui Dong, Yu Lin Huo, Fu Quan Zhang, Ting Yin, Jun Bin Du, Jian Qing Li, Yun Qing
Copyright Year	2015
Abstract	The ventrolateral periaqueductal gray (vlPAG) is an important brain area, in which 5-HTergic neurons play key roles in descending pain modulation. It has been proposed that opioid peptides within the vlPAG can excite the 5-HTergic neurons by alleviating tonic inhibition from GABAergic neurons, the so-called disinhibitory effect. However, no direct morphological evidence has been observed for the micro-circuitry among the opioid peptide-, GABA-, and 5-HT-immunoreactive (ir) profiles nor for the functional involvement of the opioid peptides in the intrinsic properties of GABAergic and 5-HTergic neurons. In the present study, through microscopic observation of triple-immunofluorescence, we firstly identified the circuitry among the endomorphin-1 (EM1, an endogenous ligand for the μ-opioid receptor)-ir terminals and GABA-ir and 5-HT-ir neurons within the rat vlPAG. The synaptic connections of these neurons were further confirmed by electron microscopy. Through the in vitro whole-cell patch-clamp method, we showed that EM1 has strong inhibitory effects on the spiking of GABAergic neurons. However, although the resting membrane potential was hyperpolarized, EM1 actually increased the firing of 5-HTergic neurons. More interestingly, EM1 strongly inhibited the excitatory input to GABAergic neurons, as well as the inhibitory input to 5-HTergic neurons. Finally, behavioral results showed that pretreatment with a GABA$_{A}$ receptor antagonist potentiated the analgesic effect of EM1, while treatment with a GABA$_{A}$ receptor agonist blocked its analgesic effect. In summary, by utilizing morphological and functional methods, we found that the analgesic effect of EM1 is largely dependent on its potent inhibition on the inhibitory inputs to 5-HTergic neurons, which overwhelms EM1’s direct inhibitory effect on 5-HTergic neurons.
Starting Page	2036
Ending Page	2053
Page Count	18
File Format	PDF
ISSN	08937648
Journal	Molecular Neurobiology
Volume Number	53
Issue Number	3
e-ISSN	15591182
Language	English
Publisher	Springer US
Publisher Date	2015-04-16
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Endomorphin Ventrolateral periaqueductal gray GABA 5-HT Disinhibition Rat Neurosciences Neurobiology Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Neurology Cellular and Molecular Neuroscience

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