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Presynaptic inhibition of excitatory synaptic transmission from the calcitonin gene-related peptide-containing parabrachial neurons to the central amygdala in mice – unexpected influence of systemic inflammation thereon

Year: 2024
Type: article
Abstract: The monosynaptic connection from the lateral parabrachial nucleus (LPB) to the central amygdala (CeA) serves as a fundamental pathway for transmitting nociceptive signals to the brain. The LPB receives nociceptive information from the dorsal horn and spinal trigeminal nucleus and sends it to the “nociceptive” CeA, which modulates pain-associated emotions and nociceptive sensitivity. To elucidate the role of densely expressed mu-opioid receptors (MORs) within this pathway, we investigated the effects of exogenously applied opioids on LPB-CeA synaptic transmission, employing optogenetics in mice expressing channelrhodopsin-2 in LPB neurons with calcitonin gene-related peptide (CGRP). A MOR agonist ([D-Ala(Kato et al., 2018) ,22N–Me-Phe(Thompson and Neugebauer, 2017),Glycinol(Aicher et al., 2013)]-enkephalin, DAMGO) significantly reduced the amplitude of light-evoked postsynaptic currents (leEPSCs), in a manner negatively correlated with an increase in the paired-pulse ratio. An inverse agonist of MORs significantly attenuated these effects. Notably, this inverse agonist significantly increased leEPSC amplitude when applied alone, an effect further amplified in mice subjected to lipopolysaccharide injection 2 h before brain isolation, yet not observed at the 24-h mark. We conclude that opioids could shut off the ascending nociceptive signal at the LPB-CeA synapse through presynaptic mechanisms. Moreover, this gating process might be modulated by endogenous opioids, and the innate immune system influences this modulation.
DOI: 10.1016/j.jphs.2024.02.004
Language: English
Field: Medicine
Open Access status: gold
Estimated APC paid: $2,070
OpenAlex ID: W4391539946
FWCI: 1.552
Cites: 45
Cited by: 6
Related to: 10