PMID- 37150382
OWN - NLM
STAT- MEDLINE
DCOM- 20230905
LR  - 20231108
IS  - 1528-8447 (Electronic)
IS  - 1526-5900 (Linking)
VI  - 24
IP  - 9
DP  - 2023 Sep
TI  - Opioids Induce Bidirectional Synaptic Plasticity in a Brainstem Pain Center in 
      the Rat.
PG  - 1664-1680
LID - S1526-5900(23)00405-4 [pii]
LID - 10.1016/j.jpain.2023.05.001 [doi]
AB  - Opioids are powerful analgesics commonly used in pain management. However, 
      opioids can induce complex neuroadaptations, including synaptic plasticity, that 
      ultimately drive severe side effects, such as pain hypersensitivity and strong 
      aversion during prolonged administration or upon drug withdrawal, even following 
      a single, brief administration. The lateral parabrachial nucleus (LPBN) in the 
      brainstem plays a key role in pain and emotional processing; yet, the effects of 
      opioids on synaptic plasticity in this area remain unexplored. Using patch-clamp 
      recordings in acute brainstem slices from male and female Sprague Dawley rats, we 
      demonstrate a concentration-dependent, bimodal effect of opioids on excitatory 
      synaptic transmission in the LPBN. While a lower concentration of DAMGO (0.5 microM) 
      induced a long-term depression of synaptic strength (low-DAMGO LTD), abrupt 
      termination of a higher concentration (10 microM) induced a long-term potentiation 
      (high-DAMGO LTP) in a subpopulation of cells. LTD involved a metabotropic 
      glutamate receptor (mGluR)-dependent mechanism; in contrast, LTP required 
      astrocytes and N-methyl-D-aspartate receptor (NMDAR) activation. Selective 
      optogenetic activation of spinal and periaqueductal gray matter (PAG) inputs to 
      the LPBN revealed that, while LTD was expressed at all parabrachial synapses 
      tested, LTP was restricted to spino-parabrachial synapses. Thus, we uncovered 
      previously unknown forms of opioid-induced long-term plasticity in the 
      parabrachial nucleus that potentially modulate some adverse effects of opioids. 
      PERSPECTIVE: We found a previously unrecognized site of opioid-induced plasticity 
      in the lateral parabrachial nucleus, a key region for pain and emotional 
      processing. Unraveling opioid-induced adaptations in parabrachial function might 
      facilitate the identification of new therapeutic measures for addressing adverse 
      effects of opioid discontinuation such as hyperalgesia and aversion.
CI  - Copyright (c) 2023 United States Association for the Study of Pain, Inc. Published 
      by Elsevier Inc. All rights reserved.
FAU - Mussetto, Valeria
AU  - Mussetto V
AD  - Department of Neurophysiology, Center for Brain Research, Medical University of 
      Vienna, 1090 Vienna, Austria.
FAU - Teuchmann, Hannah Luise
AU  - Teuchmann HL
AD  - Department of Neurophysiology, Center for Brain Research, Medical University of 
      Vienna, 1090 Vienna, Austria.
FAU - Heinke, Bernhard
AU  - Heinke B
AD  - Department of Neurophysiology, Center for Brain Research, Medical University of 
      Vienna, 1090 Vienna, Austria.
FAU - Trofimova, Lidia
AU  - Trofimova L
AD  - Department of Neurophysiology, Center for Brain Research, Medical University of 
      Vienna, 1090 Vienna, Austria.
FAU - Sandkuhler, Jurgen
AU  - Sandkuhler J
AD  - Department of Neurophysiology, Center for Brain Research, Medical University of 
      Vienna, 1090 Vienna, Austria.
FAU - Drdla-Schutting, Ruth
AU  - Drdla-Schutting R
AD  - Department of Neurophysiology, Center for Brain Research, Medical University of 
      Vienna, 1090 Vienna, Austria.
FAU - Hogri, Roni
AU  - Hogri R
AD  - Department of Neurophysiology, Center for Brain Research, Medical University of 
      Vienna, 1090 Vienna, Austria. Electronic address: roni.hogri@meduniwien.ac.at.
LA  - eng
GR  - DOC 33/FWF_/Austrian Science Fund FWF/Austria
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230506
PL  - United States
TA  - J Pain
JT  - The journal of pain
JID - 100898657
RN  - 0 (Analgesics, Opioid)
RN  - 100929-53-1 (Enkephalin, Ala(2)-MePhe(4)-Gly(5)-)
SB  - IM
MH  - Rats
MH  - Male
MH  - Female
MH  - Animals
MH  - *Analgesics, Opioid/pharmacology
MH  - Rats, Sprague-Dawley
MH  - *Pain Clinics
MH  - Enkephalin, Ala(2)-MePhe(4)-Gly(5)-/pharmacology
MH  - Neuronal Plasticity/physiology
MH  - Brain Stem
MH  - Pain
OTO - NOTNLM
OT  - Opioids
OT  - aversion
OT  - lateral parabrachial nucleus
OT  - opioid-induced hyperalgesia
OT  - synaptic plasticity
EDAT- 2023/05/08 00:41
MHDA- 2023/09/05 06:42
CRDT- 2023/05/07 19:27
PHST- 2023/03/08 00:00 [received]
PHST- 2023/04/27 00:00 [revised]
PHST- 2023/05/02 00:00 [accepted]
PHST- 2023/09/05 06:42 [medline]
PHST- 2023/05/08 00:41 [pubmed]
PHST- 2023/05/07 19:27 [entrez]
AID - S1526-5900(23)00405-4 [pii]
AID - 10.1016/j.jpain.2023.05.001 [doi]
PST - ppublish
SO  - J Pain. 2023 Sep;24(9):1664-1680. doi: 10.1016/j.jpain.2023.05.001. Epub 2023 May 
      6.